Summary of Clinical Neuropsychology by Kessels a.o. - 1st edition

Where does clinical neuropsychology come from?

A clinical neuropsychologist (in health care) focuses on the diagnosis and / or treatment of problems that are related to brain damage. Clinical neuropsychology used to be - and in some countries still is - the field of psychiatrists and neurologists. Over time, clinical neuropsychology has expanded to an independent discipline. More than 2,400 years ago, Hippocrates was convinced that behavior and feeling are the result of brain functioning. Nobody believed him and for centuries the Greeks and Romans believed that the body knew a balance between the elements of water, fire, blood and mucus. A disruption of this balance would lead to illness or abnormal behavior. Only from the 14th century (the Renaissance) did the people start to think critically.

Two notable scientists / philosophers in history:

René Descartes (1596-1650)

Descartes. The soul is an independently functioning intangible unit.

Franz Joseph Gall (1758-1828)

Gall introduced the notion that there are many mental organs in our brains. His views were tested using the clinico-anatomical method: the cognitive loss of function as a result of brain damage (in the language area, for example) was studied in patients, and subsequently the brains of patients were analyzed after their death, after which the location of the lesion was related to the type of functional impairment. Gall formed the very first foundation of clinical neuropsychology as we know it today.

What is cell theory?

The ancient Greeks distinguished between three different forms of soul. According to the ancient Greeks, man was the only one who had all three forms of the soul: a soul to survive, a soul to engage in activities, and a higher-order soul that knows the difference between good and bad. This higher-order soul - the mind - is said to be located in the empty cavities of the brain (the brain ventricles) that were called cells at the time. The first cell (sensus communis) collects all sensory information and forms an image; in the second cell the image (the psychological representation) would be interpreted: what does the image mean? The image is stored in the third cell (memoria). Cell theory has been important for the contemporary cognitive psychology. It is a general system of information processing (our mind can process all types of information) and is the same for everyone. The physiognomy, on the other hand, is about the individual differences in personality or character. Physiognomy means that someone's appearance says something about his or her personality and is attributed to Aristotle.

What did Descartes think?

Descartes renounced all the new insights that developed within the Renaissance and went alone or on what was indisputably true ("I think, so I am."). He stated that people are composed of two substances: the body (res extensa) and the mind (res cogitans), whereby the res cogitans can be seen as a kind of driver. Although the mind would be immaterial, it did place it inside a cavity in the middle of the brain: the epiphysis or the pineal gland.

What did Gall think?

Gall drew up plans for a new psychology, which he called phrenology. He assumed that all psychological functions (including knowledge and affect) are innate. He stated that the mind is not a general information processing system, but that there are specific, separate organs for music, arithmetic and even motherly love. Someone who is better at music has a larger "music organ". The organization is the same for all people (and animals): only the size can vary. His localization was based, among other things, on research into brain damage: for example, he correctly located the language in the front part right behind the eyes. His localization ideas broke with the idea of ​​one soul and Descartes' undivided mind and formed the very first basis of our neuroscience. In addition, Gall argued that the mind is not in the centre of the brain, but on the outside: the cortex. Until then the cortex was only seen as a dried-up crust with no specific function. According to Gall, the brain had independent functions, which at the time was a revolutionary idea.

What is the clinic-anatomical method?

The clinico-anatomical method was used to test Gall's localization ideas by mapping the specific loss of function and later relating them to the site of the lesion. This method was widely used in the 19th century. Paul Broca showed that patient Tan's lesion (this man could only say "tan") was not in the language area as designated by Gall, but more on the side in the left frontal lobe (Broca's area). He noticed that the lesions were almost always in the left hemisphere and he was the first to prove that we use our left hemisphere to speak. This was also the first time that an inequality of the brain halves was demonstrated. His work was universally accepted virtually without challenge. Subsequently the idea arose that the language function could be divided into sub-functions (until now, only speech production had been considered). Carl Wernicke argued that there was a separate center in the temporal lobe for recognizing (only spoken) words. From this dichotomy the distinction arose between Broca's aphasia and Wernicke's aphasia.

What is associationism?

Locke, a huge proponent of empiricism, did not believe in the innate functions as Gall, Broca, and Wernicke claimed. Locke stated that everything is learned: a vision that is also called associationism. John Hughlings-Jackson pointed out to Broca that the location of the lesion can lead to a specific failure, but that it should not be confused with the location of an entire function.

What is holism?

Around 1900 there was much opposition to the localization movement: according to Constantin von Monakow areas of the brain generally worked together. The Gestalt movement (the whole is greater than the parts) increased strongly and Henry Head called localizationists 'diagram makers', putting him in a bad light. Many counterparts of localizationism warned of a great simplification, but they did not have a good alternative: even holists accepted a certain degree of specialization. The Russian Aleksandr Luria offered them the solution in the mid-20th century by coming up with a good balance between localizationism and holism.

What did Luria think?

Luria clinically observed a lot of soldiers who had suffered brain damage during World War II. He was one of the first who focused on the rehabilitation of patients with cognitive disorders and was guided by neuropsychological theory and assessment. He described the brain as a single complex functional system in which multiple subsystems make their own contribution to joint activity. He stated that it is never possible to draw direct conclusions about the responsible subsystems: a holistic view. On the other hand, Luria was a localizationist because he was certain that an accurate analysis can show a specific disruptive factor. With his global model, Luria made a distinction between the following areas:

There are three units that are continually interacting with each other, these are related to the subcortical, posterior and anterior brain areas. The subcortical unit regulates wakefulness and attention; the posterior unit takes on the task of information processing (perception, processing and storage); the anterior unit organizes the behavior (planning, regulation and monitoring).

Within each of these units, a distinction can be made between three hierarchically organized levels of processing: the primary, secondary, and tertiary zones in the brain. The primary areas are the well-known centers for modality-specific sensory information. The secondary zones process the information and give it meaning. In the remaining tertiary zones multimodal integration, the formation of intentions, and the evaluation of one's own behavior takes place.

Although Luria emphasized that for every complex behavior intensive collaboration of both hemispheres is necessary, he denied any involvement of the non-dominant hemisphere in language and speech processes. On the other hand, he regarded the phenomenon of hemispatial neglect as one of the few symptoms exclusive to the right hemisphere.

What is a test battery?

A test battery is often used as a screening tool: cognitive functioning is systematically described in a relatively short time. A specific function is only analyzed in more detail in the event of major deviations. With such instruments, psychologists took over some of the work of the neurologists.

Which two developments contributed to the independence of neuropsychology?

Around 1960 there were two major developments in the United States. This resulted in the emergence of neuropsychology as a separate scientific discipline:

After making acquaintance with Wernicke's work, Norman Geschwind encouraged many to look for specific areas and connections to better map the functioning of the brain. He wrote an influential article about disconnections, the importance of analyzing functions and double dissociations.

Roger Sperry investigated the effects of the split-brain surgery: in patients with severe epilepsy, the fiber tract that connects the two hemispheres (corpus callosum) was cut. This kind of surgery seemed to be a surprising success: epilepsy decreased and functions such as perception, language and memory seemed intact. 

In sum: neuropsychology became an independent discipline (initially in science, but later also in health care) due to the rapid development of research into the different hemispheres and language disorders. Arthur Benton (1909-2006) was one of the fathers of clinical neuropsychology and he wrote many influential articles about patients with aphasia and other types of cognitive impairment.

What are important concepts in cognitive neuropsychology?

(Modules) An example of a module is the language module. We do not have awareness of these processes, and we do not have control over them. We can hardly even influence it. According to Jerry Fodor, a module is domain-specific, innate, encapsulated and has a fixed neural architecture. David Marr also plays a major role in the theory development of cognitive neuropsychology. Marr engaged in the rules (algorithms) that are needed to convert certain information (input) to other information (output). For example, our brain translates sounds into meaning. Marr's approach is based on serial processing: information is converted to the subsequent level of representation. Not much later it became clear that information is not strictly processed serially, but that there is also parallel processing. Influenced by Fodor and Marr, researchers started looking for models of different functions and tried to explain disorders with these models. In particular, much research was done into acquired dyslexia (John Marshall and Cox Coltheart) and agnosia (Elizabeth Warrington): an inability to recognize objects. 

What are neural networks?

Computer programs - called connectionist models - can mimic certain cognitive functions because they work in the same way as the brain: there is a large network of nodes (cells) that are connected to each other (by dendrites). Certain connections are strengthened by learning processes, which can in turn result in a particular response strengthens a response. This is congruent with the association learning of the functioning of memory. There are at least three characteristics of such models that correspond to the functioning of the brain:

• A model is 'economical' because a neural network also learns through trial and error.

• 'Graceful degradation': if certain nodes are damaged, the entire function will not be lost but part of the information will be lost.

• 'Content addressability': a small amount of the information (a few letters) can activate the entire memory trace (the whole word).

Nevertheless, it is clear that the anatomical and physiological properties of the brain differ in several important respects from those of neural networks. The networks offer little insight into how the process actually works. The model is mainly descriptive rather than explanatory. 

What is neuroimaging?

Computed tomography (CT) is an imaging technique that can detect brain injury. ‘Magnetic resonance imaging’ (MRI) significantly increased the possibilities of neuroimaging. With an ‘electro-encephalography’ (EEG) and then mainly with ‘event-related potentials’ (ERPs), more insight was gained into the functional (rather than anatomical) properties of the brain. A consequence of the development of imaging techniques was that more attention was paid to the neural correlates and physiological processes of all kinds of cognitive processes. As a result, less attention has been given to theory development.

This chapter describes the types of questions and the importance of a dissociation and double dissociation. The recovery, course and treatment are also discussed. Often it is difficult to assess whether recovery is the result of treatment or spontaneous recovery processes. Another problem in determining this is the test-retest effect: Someone can show a better performance in the second test because he / she is already familiar with the test.

What is the difference between clinical neuropsychological examination and fundamental research?

A distinction is made between clinical neuropsychological research and fundamental research. In clinical neuropsychological examinations the focus is on further characterization of the clinical picture, examining the usability of the test instruments and test procedures and analyzing the course of a disease. Fundamental research focuses on increasing the understanding of the disorder and related brain structures.

Clinically oriented neuropsychological issues

The questions in clinical neuropsychological range from differential diagnostic questions to evaluating treatments and providing answers to advice questions. Diagnostic research has to be done according to the diagnostic (empirical) cycle. A major disadvantage of research on clinical questions is that the value of the conclusion is very dependent on the quality of the test, the available standard data and other psychometric properties of both tests and questionnaires. An even bigger problem is the matter of balancing between what is practically feasible on the one hand with the optimum test combinations on the other. It is impossible to offer all the tests that would measure part of the memory; moreover, the memory remains so complex that this cannot be included in all tests. A third limitation is the missing values that are the result of a test battery that is not fully completed by the patient (due to, for example, fatigue or aphasia).

Fundamental issues

The causes of disorders and underlying cognitive processes are investigated through experimental paradigms. It is not necessary to use standardised procedures, because the comparison is made within the experiment, as the different conditions are compared.

What does a research design look like?

Subtraction

Frans Donders introduced the reaction time paradigm by applying a subtraction method: in this procedure the score (for example reaction time) is subtracted from the score or a more complex task in a simpler condition. This subtraction method is often used for imaging research. In this case, not the reaction time, but the activation level represents a score. A comment on this procedure is the unreliability of the difference score: one condition has a certain unreliability just like the other condition and these are added together. Factorial designs (analysis of variance) can be used to solve this problem.

Single and double dissociations

In neuropsychology, a dissociation implies that there is a specific dropout but general cognitive functioning is intact. With a single dissociation there is a selective dropout for task A (complex) but not for task B (simpler), while in practice it has been shown that someone who fails in task B also fails in task A. This can be explained by the fact that task A is more complex than task B: sometimes capacities are saved for simple tasks. With a double dissociation, two independent tasks are clearly distinguished that were initially thought to be strongly interdependent. For example, one patient is not able to carry out task A but is able to carry out task B while another patient is not able to carry task B, but is able to carry out task A. An example of a double dissociation is the perception of objects and the perception of spatial relationships between objects. Only a double dissociation is not sufficient evidence.

Single-case study

The patient Tan (Leborgne) and HM are well-known examples of single-case studies. Carmazza (1986) states that a single-case study is the only correct way to investigate cognitive impairment, due to the fact that no lesion (in form and impact) is the same for all individuals within a group study. In addition, it is often assumed that premorbid functioning is 'normal' in the heterogeneous group, whose focus is then on adaptability and functioning after a lesion. However, group studies are not useless: they offer a general framework and the possibility of generalization, and ultimately the single-case studies must also fall within this framework.

The design of a single-case study

There are various designs for conducting a single-case study. First, the test score of the patient can be compared with the score of a normative group. Secondly, intra-individual research can be conducted: all kinds of specific tasks are performed and the conditions are compared with each other. In this case the patient's scores will have to be compared with the scores of a control group in which participants are matched to important characteristics.

How is the course of a disease studied?

The difference between a longitudinal and a cross-sectional study

There are two main course studies that both try to make statements about the course of a disease. A longitudinal study means that one or more patients are monitored and tested for a number of years, after which their data is analyzed. An important confound - disturbance factor - here is the test-retest effect which endangers the validity of the test. The solution to this problem is to add a control group that is also tested twice at the same interval. Cross-sectional research means that different groups of patients with the same syndrome are tested at different times. In this case, the 'average course' can only be discussed. Both designs have their advantages and limitations. That is why Salthouse advocates a combined design.

Treatment studies

Treatment studies look at the specific effect of treatment through pre-measurements and post-measurements. Here it is important that generalization takes place: the improvement must not only be noticeable on objective neuropsychological tasks, but also in daily life. The difference between the follow-up measurement and the pre-measurement does not necessarily have to be caused by treatment but can be the result of a non-specific effect such as improved motivation or reduced feelings of depression. If the improvement is noticeable in a wide range of cognitive functions, the improvement appears to be caused by a non-specific effect. A solution for this is the multiple baseline design in which multiple pre-measurements are made to find out whether there is already a spontaneous recovery.

Control task and cross-over design

To assess if a specific effect occurs after treatment, a control task can be used: if a patient is treated for function A, then there should be no improvement for function B after treatment. The placebo effect should also be considered, or the Hawthorne effect, where the extra attention for the patient can lead to improved cognitive functioning. The cross-over design is a variant of the control test: here a training is given for function A, after which the performance on function A and function B is measured. Subsequently, a training is given for function B and again the performance on function A and function B is measured. The training should only lead to an improvement in the trained function.

Item-specific training

There is a specific effect if only the specific items that are trained actually improve while the other items do not improve. With specific items you can think of naming certain pictures.

Randomization test

A randomization test analyzes the probability of a certain pattern of scores when the test samples have been taken at random moments in time. For one patient, by chance, a different starting point is chosen than for the other patient. Subsequently, the course of the scores and the chance of a specific pattern are examined. It is also possible to look at two treatments within one person in this way.

Test-retest problem

One of the problems with treatment studies is the so-called learning effect. The patient may have learned item-specific. This can be solved by working with parallel versions. A test-retest effect is not so much about item-specific learning, but about task-specific learning: the patient is familiar with the instructions, the situation and knows what is to come. This must be taken into account when drawing up the design: a control group must also be offered the repeated measurements but not the treatment.

Generalization

Within neuropsychology it is important that a certain result can be generalized. This means that a learned skill in a treatment is also useful in daily practice. For this reason, it can be useful to practice tasks that (almost) exactly match reality, such as shopping. If this is not possible, it is nevertheless important to pay attention to transfer. This means that similar exercises are done, in which the patient learns how to transfer the skill to daily life.

Which quality criteria are treatments subject to?

The SCED scale contains ten quality criteria that single-case studies must meet. This includes the adequate description of clinical data, a suitable design for establishing causal relationships and the quality of the baseline measurement. A relatively new criterion has been included under the term 'randomized controlled trial' (RCT). In an RCT, the patients are randomly placed in one of the conditions (experimental or control condition).

What is neuropsychological rehabilitation?

After acquired brain injury (ABI) there is always some degree of spontaneous recovery. To what extent can treatment (or neuropsychological rehabilitation) promote recovery? There are many methods that fall within neuropsychological rehabilitation, but it has to be given by a neuropsychologist, and medicinal or medical treatments are not included.

What is important to remember about recovery and plasticity?

Recovery is not the same as a complete return to the level of functioning such as before the brain injury. Recovery is an improvement in cognitive performance compared to the condition during and immediately after the injury.

Recovery after brain injury

Most recovery takes place in the first months after the ABI, and after a year there is hardly any improvement. This is the neurological end state. Behavioral functioning can still improve in the long term, because patients learn to cope better with their limitations. In this context, recovery takes place on a behavioral and psychological level. At the time of the neurological end state, there will be negative and / or positive residual symptoms according to Hughlings-Jackson (1888). Negative symptoms refer to loss of function; Positive symptoms include the patient's attempts to deal with this functional loss (the coping strategy). Goldstein (1942) renamed this dichotomy as direct versus indirect symptoms respectively. The dichotomy in symptoms fits well with the dichotomy of recovery: if the direct symptoms recover, there is recovery at the neurological level, while the indirect symptoms manifest themselves at the behavioral level of recovery. Subsequently, there is also a distinction between approaches to neuropsychological rehabilitation: the restorative approach is mainly focused on achieving recovery at the neurological level, while the compensatory approach tries to promote recovery at the psychological level. The coping strategies and other compensatory methods will also result in changes at brain level in the long term.

Types of plasticity

The developmental stage of the brain is key to plasticity processes. On the one hand, the Kennard principle states that prognosis after brain damage is better at a young age than when this damage is sustained later in life. On the other hand, there is the double hazard hypothesis that younger children with contracted brain injury have the worst prognosis. Many underestimate the severity of the impact if the brain injury develops early in life, because children often experience the real nature of their defects later in life (partly because the executive functions are not fully grown until around the fourteenth year). For example, indicators for dyslexia are already present at brain level, but this is only noticed once the child learns to read. This is called 'growing into deficit'.

Neural plasticity

Neural plasticity affects the entire brain and is a continuous and lifelong process in which all learning experiences create new connections or strengthen old ones. An experienced taxi driver, who needs a lot of spatial insight because he constantly has to drive new routes, has more volume of gray matter in the hippocampal areas than bus drivers who only drive fixed routes. The years of driving experience correlated with the hippocampal changes. Learning new spatial skills seems to be at the expense of this positive adaptation (Maguire, Woollett & Spiers, 2006). Learning complex tasks influences the plasticity of the brain: experienced piano players have a larger dendritic network in motor, auditory and visual-spatial areas of the brain (Gaser & Schlaug, 2003). Even without active interventions, the brain shows plasticity. This is mainly noticeable in the spontaneous recovery. The most likely explanatory hypothesis is restitutive reconnection. This hypothesis suggests that neurons in areas adjacent to the damaged area quickly create new neural connections in order to replace lost connections. Kolb (1995) suggested that this restitutive reconnection is possible when there is a minor injury, but for serious injuries the recovery is mainly achieved at the behavioral and psychological level (Robertson and Murre (1999) state the same as Kolb).

How can plasticity be stimulated?

According to Robertson and Murre (1999), different types of focused stimulation are the most effective way of stimulating the plasticity of the brain after brain injury. An example of this is bottom-up stimulation, in which external stimuli are administered in an attempt to stimulate the formation of new neural connections. The goal is that new neural connections will be made, which is in line with the idea of ​​''cells that wire together, fire together". Unfortunately, little research has been done into the stimulation of neuroplasticity. 

What is learning?

Rehabilitation is (re)learning. The purpose of a learning process is a relatively permanent change in behaviour that is the result of experience. To achieve this goal, frequent and correct associations must be made between the triggering factor (the stimulus) and the desired behavior (the response). According to Shiffrin and Schneider (1977), if the triggering factor and the behavior occur repeatedly in the same combination, the strong connection is made. This is called "consistent mapping". When multiple responses are triggered by the same stimulus, there is no learning outcome. This is called "varied mapping". Mulder (1992) talks about the importance of direct verbal feedback on the learning process, such as “knowledge of results” (KR): to what extent has the learning objective been achieved and how can it be done more efficiently, or how is the object achieved? "State-dependent learning" means that learned behavior is applied more easily if the situation in which the behavior is desired shows strong similarities with the situation in which this behavior is learned. In this case, there must be a transfer from one situation to another, or (more preferably) a generalization of the learned behavior to all other situations in which this behavior is desired. Learning behavior must therefore be anchored as much as possible, but independent of the specific context. There are two ways to stimulate the transfer to a different context. The first is "variability of practice" (VP): variations can be made to the learning context early in the learning process. The second is "linkage to the site of application" (LA): during the learning process, learning behavior in the learning phase is already related to the target situation in which that behavior is desired.

The ICIDH model

The Internal Classification of Impairments, Disabilities and Handicaps (ICIDH) model is a WHO classificated system that dates back to 1980 and subdivides the behavioral consequences of illness and injury into three different levels: impairments, disabilities, and handicaps. Disabilities are the consequences of impairments at a personal level. They relate to all the activities that can be carried out by a person and that can be affected by the impairment. A handicap refers to an adverse effect on societal functioning as a result of an impairment and a disability; it is a restriction that hinders the patient's normal role fulfilment. In 2001 the successor of the ICIDH was introduced, namely the ICF. The main difference is that the ICF model is based on overall health (as opposed to only illness and / or injury) and there is also room to describe the consequences of an illness and / or injury in positive terms. The ICF describes functioning in terms of body functions, activities and participation, and both environmental and personal factors can be mapped.

Neuropsychological intervention.

Gross and Schutz (1986) distinguish different levels of learning ability. These different levels are:

1. The level of learning ability.

2. Influencing behaviour using conditioning.

3. Skill training.

4. Strategy training.

The degree of learnability is mainly dependent on the extent to which the executive functions are intact and the patient's insight into the disorder and its consequences (the latter determines the motivation). Below is an overview of the relationship between five training options and four possible effects. At the first level, the environment is adjusted and the patient's learning capacity is nil.

Example: marking the route from the bedroom to the toilet with red dots on the floor. SR conditioning is equal to stimulus-response conditioning. Here, instrumental conditioning is used (making a link between a stimulus and a response) or operant conditioning (influencing the frequency of the desired behavior by means of reinforcement or punishment). A behavioral routine is taught. On the third level, situation-based behavioral routines and activities are trained that consist of several actions. Compensation strategies are only taught at the fourth level. Here a considerable input from the individual is required and the external structure is less important. A cognitive cycle is used at the highest and fourth levels: the patient can set realistic learning objectives, make plans and execute and provide feedback.

What is neuropsychological rehabilitation?

The difference between the recovery model and the compensatory model

First, the recovery model was the most popular model, based on training aimed at repairing the damage in cognitive function and the underlying brain structure. Lashley, Goldstein and Luria are well-known names. In the first place, it was thought that the effect of targeted training would be generalizable. The compensatory model, on the other hand, assumes that neural damage is irreversible; does the treatment not only focus on the individual but also on the environment (as long as it benefits the patient), and; treatment does not focus on the disorder itself but on the consequences in daily life and improving functioning at participation level and activity level.

Job training?

Every training within the recovery model is a functional training. During a function training the patient must continuously perform the same task. This is called the 'repeated practice approach'. This method is also used to train damaged muscles. For this reason, it is also called the 'mental muscle approach'. Other names for the same type of training are: cognitive retraining, 'mental bodybuilding', brain gymnastics, 'drill and practice' and ''stimulation training''. However, the training should have an effect on the underlying brain function. This is not apparent from the task-specific results. Cicerone and colleagues (2005) stated that there is no effective treatment within the restorative approach yet.

Compensatory treatments

There is a lot of supporting evidence for treatment methods that fall within the compensatory treatment. Skill training is a compensatory method that trains situation-related skills: just as with functional training, one action is trained each time but the underlying purpose of both forms is completely different. If a patient has sufficient executive capacities, a top-down approach can be chosen: the strategy training (such as “coping with time pressure”). The patient has to perform a number of steps or ask himself a number of questions in a situation (such as "preparing a meal").

Further intervention options

In psychoeducation, the patient is provided with explanations and information about the consequences of the brain injury in general, as well as the consequences for that particular patient. The latter is based on the strength-weakness analysis of the patient's functioning. This analysis is achieved using neuropsychological assessment. Because of psychoeducation the patient is somewhat reassured about the 'normal' consequences of the brain injury and the patient gains (more) insight into his limitations (the motivation for the treatment can be increased by this). Environmental modifications are the changes that have to be made to the physical and social environment so that the patient is provided with structure to enable them to function as well as possible with their disability. Finally, neuropsychotherapy is also part of a neuropsychological treatment. This therapy is aimed at the specific emotional and psychosocial problems of patients with brain injury. Sometimes this also includes behavioural modification. This means that unwanted behavior is extinguished and desired behavior is promoted.

What does spatial cognition imply?

Spatial cognition is not just one domain: it includes focusing on various locations in space, integrating visual information, and manipulating objects in space, both perceptually and in memory.

Spatial perception

The dorsal, so called 'where' route is mainly specialized in spatial information, while the ventral 'what' route is mainly involved in processing the identity of objects. Milner and Goodale (1995) discovered that these routes both had a different purpose: the dorsal route is 'vision-for-action' (because the information flow would go directly to the motor system) while the ventral route is 'vision for perception'. Any similar dichotomy is actually a strong simplification of reality and should be used with caution.

Spatial attention

Spatial attention is the term given to the ability to direct attention to stimuli in space. In Posner's attention model spatial information processing holds an important place. He distinguishes between stimulus-driven "covert orienting" (our attention is automatically drawn by spatial stimuli) and top-down "overt orienting" (aspects of spatial attention that require executive control).

Spatial representations

A commonly used dichotomy of possible spatial representations is between egocentric and allocentric representations. When we take ourselves as a frame of reference, we use a self-centered representation. When there is a bird's eye view / mental map, we speak of an allocentric representation. Kosslyn (1994) states that our spatial representations are made through categorical information processing or through coordinated information processing. In categorical information processing, the left hemisphere is primarily involved and the relative spatial relationship between objects is central ("the glasses are in the drawer"). Coordinated information processing has a more metric character in which spatial relationships are expressed using coordinates. The right brain hemisphere specializes in the processing of fine-grained coordinates ("the glasses are 25 centimeters to the left of the book").

Spatial memory

Spatial memory covers three sub-domains: spatial working memory, object-location memory, and the learning and remembering of routes. When learning and remembering routes, a combination of egocentric and allocentric knowledge is of great importance (Burgess, 2006). Research into learning and remembering a route is often done by using a virtual maze in which objects serve as "landmarks". If a subject is placed in a maze, the allocentric knowledge can be tested by means of the landmarks because a field-dependent egocentric representation is no longer sufficient.

The visual-spatial sketchpad and mental rotation

Spatial working memory holds the spatial information for a short period and manipulates it. Dynamic spatial information would primarily rely on the spatial working memory, while static information is more concerned with the visual working memory. Within Baddeley's model, the visual-spatial sketchpad is responsible for this same function. Analogously to the number span, the block span measures the capacity of this sketchpad. An important function of the visual-spatial sketchpad is mental rotation. This means that people can manipulate a mental image in such a way that it can be presented in a different way.

Memory for objects and their locations

The memory for object locations is part of episodic memory. Research into brain injury patients has shown dissociations between different parts of the object-location memory.

How is a route learned?

Learning a route is another important part of spatial memory, and it involves all the above-mentioned spatial memory processes. Learning a route involves the use of landmarks, which relies on memory for object locations. Moreover, a combination of egocentric and allocentric knowledge is needed.

Visuospatial praxis

Visuospatial praxis and visuospatial planning are important parts of spatial cognition. Visuoconstructive praxis consists of skills that combine perception, memory, and planning with motor responses. These concepts are discussed further in later chapters.

What are consequences of impairments in spatial perception?

Simultanagnosia is a disorder whereby spatial perception is impaired. Patients suffering from this disorder do not have an overview of the world around them: they only see part of the visual scene at any given time. A distinction is made between ventral simultanagnosia and dorsal simultanagnosia (Farah, 1990). Ventral simultanagnosia is related to damage in the left inferior temporo-occipital or left occipital brain regions. Patients can observe multiple objects at the same time, but cannot recognize and / or interpret a scene as such. Another characteristic of this patient group is that they read letter-by-letter. Patients with dorsal simultanagnosia often have bilateral damage in the parietal-occipital or parietal areas of the brain. These patients use the identification of certain parts of an object to infer something about the whole object. They have difficulty locating the stimuli.

Which disorders can be distinguished within spatial attention?

Neglect

Unilateral neglect is a known attention disorder in which there is a delayed or even no response to stimuli on the contralateral side of the brain injury. Neglect can be a supramodal disorder, but in most cases it is limited to visual modality. Neglect occurs after both left and right hemispheric lesions, but is clearly more persistent after right hemispheric injury. In the acute phase, half of all patients have a forced position of the head and / or eyes to the right. The underlying mechanism of this is the exaggerated attention they have to stimuli in the ipsilateral side. Most patients also suffer from anosognosia while others suffer from anosodiaphoria (the latter group is aware of the disorder but is not concerned about it). Tasks to determine visual neglect are mostly cancellation tasks. There are various forms of neglect, and they almost always occur only after major brain injuries. Nevertheless, the critical lesion location for neglect is the right gyrus temporalis superior. There is no consensus on this. Account must be taken of the fact that neglect has many subtypes and it is a heterogeneous disorder that can manifest itself in multiple ways. Due to the size of the lesion, neglect often accompanies hemiparesis / hemiplegia and hemianopsia / visual field defects.

Extinction

The term extinction is used when neglect patients recover. They are often gradually able to detect and identify unilateral, visual, aural, or tactile stimuli on the neglected side, but they do not notice these stimuli in the case of simultaneous bilateral stimulation. The confrontation method is used to test this: the patient has to concentrate on the researcher's nose, while the researcher briefly moves one or two index fingers in the patient's left and right peripheral visual field.

What disorders are distinguishable within spatial memory?

Many types of neurological damage can lead to an impaired spatial working memory. There is functional functionalization within the working memory: a patient with a right parietal lobe lesion performs worse on the Corsi Blocks Test than a patient with a left parietal lobe lesion. Even after a frontal dysfunction (schizophrenia) or a frontal lesion, a disturbance can occur in the spatial working memory due to the involvement of the executive functions. The problems mainly manifest themselves on tasks where object and location information must be combined. Most tasks that only use spatial memory, such as mental rotation tasks, mainly involve the parietal cortex. Cognitive aging also has a major influence on the deterioration of the spatial working memory.

What disorders are there within the object-location memory?

If the medial temporal lobe or structures in the diencephalon are impaired, there is a disorder specific to the object location memory: patients with a right hippocampal lesion in particular perform significantly worse on tasks where the location of an object has to be remembered. If the damage is positioned in the right hemisphere, the patient performs worse when the "coordinated" positional information has to be withheld; if the damage is in the left hemisphere, the categorical object information is worse associated with the position (this is a double dissociation).

Topographical disorientation?

A disorder that often occurs in patients with a neurodegenerative disorder is topographic disorientation: these patients have difficulty navigating, learning a route or finding their way back after a right or left hemispheric lesion (the latter is rarer). It is not a unitary disorder, so several sub-processes can be selectively disturbed (Farah, 2003).

• Egocentric disorientation: This disorder is the result of a lesion in which the junction of the posterior parietal lobe and the occipital lobe is damaged. Patients have difficulty estimating the relative location of objects relative to themselves.

• Disorientation in direction / ‘Heading disorientation’: This specific disorder is the result of a damaged posterior gyrus cinguli. Patients have difficulty observing and remembering "landmarks" and their relative orientation.

• ‘Landmark’ agnosia: In this specific disorder, the patient has difficulty recognizing "landmarks".

• Anterograde disorientation: The critical lesion location is the right gyrus parahippocampalis. New routes cannot be learned.

• Left-Right Confusion: This specific spatial orientation disorder mainly occurs in Alzheimer's patients and is also the fourth characteristic of the Gerstmann syndrome (in addition to finger diagnosis, acalculia and agraphy) in the case of left-hemispheric parietal lobe damage.

Learning a route is measured within a clinic with maze tasks or a virtual-reality computer task; outside the clinic, patients are asked to actually walk a specific route and walk back.

Which disorders are distinguishable within spatial praxis?

Constructive apraxia

Simple drawing tasks such as drawing or copying a three-dimensional cube may be greatly affected by the lack of education of healthy elderly people, and are therefore not suitable for establishing constructive impairments within the frame of Alzheimer's disease. A patient with a constructive apraxia simplifies a drawing, extends certain parts and draws the copy very close or even on top of the original (the latter being the phenomenon called "closing in"). Patients often have a left or right posterior parietal and / or occipital cortex lesion. A patient with a lesion in the left hemisphere may be able to make a symmetrical drawing (this patient does have an overview), but has much more trouble filling in the details. A patient with a lesion in the right hemisphere has difficulty drawing symmetrical and often loses the overview of the task.

Optical ataxia and Bálint's syndrome

If a patient has difficulty reaching and grasping visual objects in the peripheral visual field, this person suffers from a pure optic ataxia. This disorder is the result of unilateral or bilateral damage to the parietal cortex (and in particular the superior parietal lobe and the intracietal sulcus). After unilateral injury, the patient often has a contralateral visual field defect in addition to the pure optical ataxia that manifests itself in the field contralateral to the lesion. The simplest way to detect optic ataxia is by comparing grasping conditions inside and outside of the central field of vision with each other while the patient is focusing on the researcher's face. These grasping and reaching problems are modality specific: for example, patients can experience difficulty in grasping at visual targets, they usually have no difficulty in reaching for the location of aural or somatosensory stimuli when they are blindfolded. Patients with Bálint-Holmes syndrome (or Bálint syndrome) have three disorders: dorsal simultan agnosia, optic ataxia, and oculomotor apraxia. Patients appear to be blind because they bump into everything, and are often unaware of objects unless these are centrally positioned in their field of vision. Their perceptual experience is a chaotic succession of single objects (they cannot process more than one stimulus at a time). The Bálint syndrome is the result of bilateral damage to the occipito-parietal area in the dorsal route, but each of the syndromes has a separate pathophysiological substrate (demonstrated by double dissociations for each of the disorders).

What does spatial cognition look like?

Spatial cognitive functions use several systems, each of which has a different neural subsystem for processing a specific aspect of spatial cognition. In a global model, the following brain systems with associated spatial cognitive functions can be distinguished:

The frontal lobe plays a major role in spatial working memory, integrating information and spatial-temporal learning

The posterior temporal lobe is involved in the 'where' route, the egocentric coding, the categorical relationships (left hemisphere) and coordinated relationships (right hemisphere) and in spatial localization and attention

The temporal lobe is related to the 'what' route, and shape and object recognition

The hippocampus is involved in allocentric coding, and linking the object and the location (object-location binding)

Why is knowledge of language important?

Every year a lot of cerebrovascular accidents (CVAs) occur, and around 20% of these cases involve language or speech impairments. Since CVAs are very common at later ages, the prevalence will increase in the future.

What does communication consist of?

After speech, writing is the most used medium to transfer messages to other human beings in order to communicate. According to Crystal (1992) language is systematic (bound by rules), conventional (based on agreements) and symbolic (words refer to an arbitrary concept). Language does not necessarily have to be communicative (this could include self-expression, such as the writing of a poem or the singing of a song). The characteristic that primarily makes human language unique is that it uses limited resources. Words can be combined over and over again in new ways in grammatically organised sequences.

What is the cognition of language?

Language is a cognitive system. The system starts producing language by a pre-verbal message and ends with an acoustic or graphic form. A message must also be understood. A form is observed, which ends in a mental representation.

The mental lexicon

The mental lexicon is similar to a mental dictionary and is part of the semantic memory system. Not only single words but also sentences and expressions that we use frequently are stored as a whole in our lexicon. There are three types of information available for each saved word: attributes related to meaning (the concept), grammatical attributes, and characteristics relating to form. The attributes relating to meaning are organized on the basis of characteristic agreements ("cat" is linked to the concept of "dog" but also to the concept of "cat food"). The information about grammatical attributes has to be stored in the lexicon as one of the grammatical characteristics of a word. The representation of the grammatical characteristics of a word is often called a 'lemma'. The characteristics relating to form are represented in the lexicon by abstract units of sound that are called 'phonemes'.

How is language processed?

The sound waves that are caused by speech vary in amplitude (the loudness) and the speed or frequency (the pitch). Phonemes can be identified based on these differences. The mental lexicon then searches for a word (series of phonemes) that matches the word just heard. All words that partly match the word are activated (with the word "''inquiry" the words "ink, choir, inquire, inquiry, why, wire, and wiry" become active). These words compete with the target word to be recognized and are called candidate words. As soon as word recognition takes place (the target word has won) the grammatical and meaning characteristics become available. The language system then determines the meaning of a sentence by looking at how each word relates to preceding and following words: this process is called "parsing."

How is language produced?

According to Levelt's language production system (1989), the "conceptualiser" is the mechanism responsible for choosing a message to communicate. This message is then only an abstract idea, but it does contain enough information to activate words in the lexicon. The “formulator” casts the message in a grammatical form: the grammatical coding takes place. To quote the book: this series is 'dressed' with sound information: the phonological coding. This phonetic plan (inner speech) travels to the next level: the "articulator" where the articulation organs (the larynx, the tongue, the lower jaw and the lips) convert the plan into sound. The "monitor" monitors whether the message is spoken loud enough, whether the utterance is grammatically correct, whether the speech is loud enough, and so on. 

What kinds of language impairments can be distinguished?

Aphasia

An aphasia is a collective term for acquired language impairments, which are usually expressed in all modalities. Aphasia is commonly caused by a stroke; less often the cause is found in traumatic brain injury or a brain tumor. The result is a focal, localised trauma.

Impairments known within language production

People with aphasia have impairments in language production, including major word problems. As a result, they omit words (omissions) or replace the word they are looking for with another word (replacement). Substitutions (paraphasias) can be expressed in various forms:

• A lexical paraphasia: the target word is replaced by an existing word which is usually (but not always) related to the target word (chosen from the same semantic network).

• A phonological paraphasia: at least one sound of the target word is omitted or replaced by another sound which often results in a non-existing word. A 'neologism' is a word of which it is unclear what it represents, because of the large amount of replaced or omitted sounds. If a patient uses a lot of neologism, he / she speaks in 'jargon'.

Sometimes the aphasia is so serious that meaningful speech is no longer present. The patient then switches to a form of 'non-propositional speech':

• 'Stereotype': the patient frequently uses expressions that have little meaning and are irrelevant to the communication, such as "I don't know" or "how do you say that?" with a lack of other meaningful sentences.

• 'Recurring utterances': the patient produces one or more utterances (sounds, words, or sentences) in all kinds of inappropriate situations (using the phrase 'Marks and Spencer' for everything). 

• 'Serial speech': the patient can still finish common, well-memorised strings (speech therapist: “1..2..3..4..5..6 ..”, patient: “..7..8. .9 ... 10 ")

• Echolalia: the patient repeats what their conversation partner says. This can consist of entire sentences or, for example, the last word. 

• Perseveration: the patient involuntarily repeats words or phrases.

Forms of syntax

There are two forms of syntax problems that often occur with aphasia patients:

1. Agrammatism: patients have difficulty using the grammatical knowledge correctly. The grammar repertoire is therefore very limited and patients only use short, easy sentences (telegram style). Example: Girl ... walk... home.

2. Paragrammatism: the sentences are long and complex. The sentences are very difficult to understand because of the large number of paraphasias as well as the incorrect use of conjugations, declensions, and function words. Example: Yes it is the language you know it stays where it is when I when you talk to me then I need sometimes one hour need I to say what I would like to say that's non nonsense. 

Which impairments are known in language comprehension?

Some aphasia patients have difficulty distinguishing phonemes: if they have to point to a pea, and that picture shows both a bee and a pea, then they have difficulty choosing between them. Problems can arise not only at the sound and word level, but also at sentence level. Especially when it cannot be deduced from the independent words of the sentence who does what, the sentences are difficult to understand. Example from the book: "The boy is kissed by the girl": the words "boy", "girl" and "kiss" do not indicate who is being kissed. Such sentences are 'reversible passives' where patients with aphasia have to guess the meaning ('agrammatical comprehension'). With a sentence like "The girl pours the tea" it is clear that the tea is poured by the girl: there is only one common meaning.

How can aphasia be classified?

The taxonomy influenced by Broca, Wernicke and Lichtheim - 'classical aphasiology' is the most widely used taxonomy of aphasia.

• Broca's aphasia: the language concept is intact. Patients have a lot of trouble with articulation and finding the right words, so the speech rate is very low. Often the patients are agrammatic. They have difficulty repeating.

• Wernicke's aphasia: speech is fluent, but the language concept is strongly affected. There are many phonological and semantic paraphasias and often there is paragrammatism. There is little insight into the disease here. The patient talks a lot but says little. Here too repeating is affected.

• Conduction aphasia: the language concept is fairly intact and the language production is similar to that of Wernicke's aphasia. The biggest problem in this case is repeating spoken words. Patients do have disease insight because they are trying to correct their mistakes. This helps: a phenomenon called "conduite d'approche".

• Transcortical aphasia: in sensory transcortical aphasia there are problems in language comprehension (as with Wernicke), and production, but repeating is intact. In motor transcortical aphasia, the patient experiences problems in language production (such as with Broca), not in language comprehension and repetition is also intact.

• Global aphasia: both production and comprehension are affected. 

• Amnestic aphasia: language production and language comprehension are intact (no agrammatism, paragrammatism, or paraphasias). However, there is a very serious problem in finding the right words. This mainly concerns nouns, while in other forms of aphasia the problem of finding words is mainly the verbs.

Only 25% of all aphasia patients have a pure aphasia syndrome: most have a mixed form.

The PALPA model

The descriptions of the symptoms of aphasia patients from Ellis and Young (1988) formed the basis of the PALPA model (a test battery). The PALPA model distinguishes many highly specialized processing modules. Each module can be lost after damage. A careful inventory can be used to determine precisely which module is affected in the language processing system. This model recognizes the complexity of the language system. This model is mainly theoretical because a neural substrate has not yet been identified for each component.

What are speech impairments?

'Dyspraxia' and 'dysarthria' are speech disorders that often coexist with aphasia. With a verbal dyspraxia something goes wrong in the programming of the articulation organs. The language system is intact and the articulation organs are also intact, but the articulatory movements are imprecise and uncoordinated. Longer words are much harder to pronounce than shorter words. Sequences of sounds are also major challenges. Dysarthria is a generic name for speech impairments that are caused by a lack of control over the articulation muscles as a result of damage to the motor part of the central nervous system or the peripheral nervous system. Muscle impairment itself may also be a cause of dysarthria. Different types of dysarthria are known, and in each type, damage in located in another brain area. 

What kinds of reading impairments do exist?

Aphasia patients often have acquired dyslexia: a collective name for some specific types of reading disorders. The following types are common:

• Attention dyslexia: the patient cannot name the individual letters.

• Neglect dyslexia / positional dyslexia: the patient reads the letters of one half of the word incorrectly, causing him / her to make many mistakes when reading.

• Semantic dyslexia / deep dyslexia: the patient does not read the written word, but a word that is semantically related to that word.

• Phonological dyslexia: the patient can read existing words, but cannot read pseudo words (non-existent words).

• Surface or surface dyslexia: the patient can read all words, but regularly spelled words are much better read than irregularly spelled words.

Which writing disorders are there?

Writing problems that occur in aphasia patients are the following:

• Phonological dysgraphia: pseudo words cannot be written down.

• Surface dysgraphia: regularly spelled words are better written than irregularly spelled words.

• Graphemic buffer dysgraphia: the word form is intact but the letters are replaced by other (incorrect) letters or the order of letters is reversed

What are new insights in the neurocognition of language?

Damage in frontal areas causes disrupted speech production (Broca's aphasia) because the articulatory patterns of words are located in this area, near the areas that control the tongue and mouth. Damage in posterior parts of the brain disrupts the concept of language (Wernicke's aphasia) because the sound images of words are stored in the posterior areas around the auditory processing area. This model, elaborated by Wernicke, was later expanded by Lichtheim (1885). Contemporary insights reveal that the Wernicke-Lichtheim schema is very simplified because it is assumed that there is a one-to-one relationship between disorder and tissue damage. Three nuances that must be applied are therefore the following:

• Broca's territory is not specifically linked to language production, just like Wernicke's territory is not specifically linked to language comprehension.

• There is indeed involvement of the right hemisphere.

• The 'language centers' are also involved in other processes.

How are emotion and social cognition connected to each other?

There is a lot of supporting evidence for the idea that cognition and emotion are two specific, functionally different types of information processing, that do, however, interact to a great extent. Emotion is a precondition for motivation.

What are social interactions?

Social situations are complex, dynamic, and they involve time pressure. Social cognition is a term used to refer to all mental processes that underlie social interactions (Brothers, 1990). All mental processes involved in social cognition can be divided in three stages: perception (involves the focusing of attention on and the perception of relevant information, including: non-verbal social signals, verbal social signals, and contextual information), interpretation (including the allocation of meaning to social schemas, the formation of social concepts, 'mentalising', empathy, imitation and simulation, and social, causal attributions), and reaction ( response selection and implementation of social behaviour).

What are emotions?

An emotion is both a physical and mental state that is related to feelings, thoughts and behavior. A distinction can be made between emotions (which refer purely to the physical reactions that all mammals have) and feelings (the human subjective experience of emotions). In this sense, an emotion is a brain function that detects important information and prepares the body to respond with the highest chance of survival (such as a flight response).

How can emotions be classified?

Emotions can be classified on different axes, such as positive versus negative, 'approach' (extraversion) versus 'withdrawal' (introversion), and high intensity versus low intensity. A widely used distinction is the difference between the primary and secondary emotions. The six primary emotions include happiness, anger, fear, sadness, disgust, and surprise. The underlying neural circuit for these emotions is mainly formed by the subcortical structures. A certain form of specialization can be seen within this: the amygdala is most strongly involved in fear, the cingulate gyrus in sadness and anger, the insula in disgust, and the basal ganglia in happiness (Phan, Wager, Taylor & Liberzon, 2002). All primary emotions are universally recognized in the facial expressions (Ekman, 1999). The secondary emotions (social or moral) regulate behavior in general in order to prevent social exclusion and to facilitate adaptation to the group. For example, feelings of guilt, shame, jealousy, disapproval, and contempt.

The functions of emotions

Emotions increase our chance of survival by preparing our bodies for a flight-or-fight reaction. The amygdala has an important in processing threatening external stimuli. According to LeDoux's two-route model (1996), the threatening information can be processed via two routes; both end in the amygdala that triggers the physiological reactions:

• The fast route: the global information is sent directly from the thalamus (a “central distribution station”) to the amygdala.

• The slow route: the global information from the thalamus first passes through the frontal cortex so that the information can be specified. Then the information is sent to the amygdala. Due to the fact that the specification of information is done via the frontal cortex and this cortex has strong connections with the hippocampus, it is also possible to learn from this threatening situation. The amygdala also has strong connections with the hippocampus: this connection explains why emotional events are often better remembered than non-emotional events.

The emotion is mainly expressed in the facial expression, but also the body posture, gestures, voice intonation, and olfactory stimuli such as pheromones convey emotional information.

The influence of emotions on behavior

An emotion automatically triggers a physical response (via the fast route): in this way our behavior is unconsciously influenced by our emotions. The functional importance of the primary emotions is self-evident (the goal is survival), but for secondary emotions, the functionality of the physical reactions is not so clear. According to Damasio's (1994) somatic marker theory, the physical reactions in a complex and unclear situation lead to a 'gut feeling' (intuition) with which you can make decisions. A test that analyses how physical responses are used to guide decisions is the Iowa Gambling Task. This objective task also shows that the somatic markers (the physiological internal processes) are interpreted as warnings (Damasio's 'gut feeling'), which means that certain options are avoided. In this task, the patient learns that certain choices have negative consequences. Patients with amygdala damage do not receive any physiological reactions and therefore no gut feeling. It has also been found that patients with damage to the ventromedial prefrontal cortex (VMPFC) do generate the somatic stamps, but that they can only do this after making a choice and not before. From this it can be concluded that not only the amygdala, but also the VMPFC is related to the generation of emotional physiological responses (Bechara, Damasio, Damasio & Lee, 1999).

How are emotions regulated?

There is an (conscious, active) intentional and an (unconscious, passive) unintentional form of emotion regulation. Intentional regulation, especially the regulation mechanic-sective reassessment (reappraisal and affective suppression) are applied. In affective reappraisal, the patient interprets the situation more positively. The reappraisal, unlike the suppression, takes place before the emotional response which can change the emotion process, which explains why the revaluation is often a more effective emotion regulation method. Prefrontal cortex activation is increased, and activation of subcortical areas such as the amygdala is reduced. 

Self-reflection

Self-reflection and self-awareness make it possible to actively seek out situations in which we feel good and avoid situations in which we feel bad. Both are related to activation in the VMPFC. Patients with damage in the VMPFC often have fewer self-aware emotions (such as shame after inappropriate behavior), difficulty in assessing their own (social) functioning, planning and decision making (Damasio, Tranel & Damasio, 1990).

What is mentalising?

The ability to 'put ourselves in other people's shoes' is called "mentalising." Two different concepts are of importance: mirroring the experiences and feelings of other people on the one hand, and attributing thoughts, intentions, aims, and desires to them (Theory of mind) on the other. 

The mirror system

Internal simulation, or the introduction of affective, motor or perceptual experiences, can help us to understand other people better. With internal simulation we can become happy by looking at someone else who is happy. This link between perception and one's own experiences is made possible in part by the mirror system: a system with a shared representation for perception and action. The mirror system is probably the underlying mechanism for empathy.

Theory of Mind

In "Theory of Mind’ (ToM), the person forms a hypothesis about the thoughts of others by taking their perspective. In a complex mental experience of someone else it is not enough to mirror someone's experiences: abstract and semantic representations are needed to find out the intentions and to understand the situation. Within the ToM there is a ‘first-order belief’ and a ‘second-order belief’.

The first order belief ("Suus thinks that her mother is going to pick her up from school") develops around the third year of life and turns into being able to think about ‘something’. The second order belief ("Mark thinks that the teacher thinks that he hasn't made his homework") Develops around the age of six and turns into thinking about thinking. Often it is difficult to understand a social ‘faux pas’: here someone else's unintended social misstep must be recognized as such and the perpetrator must be recognized to not intend to hurt someone else (Stone, Baron-Cohen & Knight, 1998).

The recognition of a faux-pas situation can only take place from the age of 8. The brain area that is most activated in studies to ToM is the medial prefrontal cortex (MPFC): an area known for its involvement in the integration of information. The MPFC becomes active in condemning yourself and in judging someone else. The only person responsible for the ToM includes the parts involved in executive functions (reasoning, cognitive control), language and the reading of affective information based on facial expressions.

Which neurocognitive models of social behavior are known?

The SOCIAL model

The ‘Socio-Cognitive Integration of Abilities’ (SOCIAL) model by Beauchamp and Anderson (2010) states that social skills are mediated by a neural network that is susceptible to environmental factors. The model contains three components. The first component consists of the mediating factors: internal factors (such as personality) and external factors (such as culture) that shape social skills. The internal and external factors interact with the brain. The second component covers all emotion processes and cognitive processes that are related to social behavior. These processes form one strong system that are interconnected at neural and behavioral level. This component can be divided into three categories:

1. Category 1: Attention and executive functioning (such as working memory and inhibition)

2. Category 2: Communication skills (such as the viewing direction and language comprehension)

3. Category 3: Social-emotional functions (such as mentalising (ToM) and empathy)

The second component forms the basis of social competence: the third component. Social competence equals social skills, social adaptation, and social development. It concerns the aim of meeting the requirements of the social environment.

Which emotional impairments can occur?

Due to the fact that social cognition is so broad, the heterogeneity of the disorders is enormous. Often an abrupt or gradual experience in social behavior is most quickly noticed by the environment. A key aspect is that according to the environment, the patient has become more self-centered (a change in character). He / she no longer takes other people into account, and shows no interest in the people around. Their relationships lack reciprocity. The emotion has blunted (which can be referred to as pseudodepression because there is no suffering pressure) and there is virtually no insight into illness. Child-like behavior, Witzelsucht (the tendency to constantly make inappropriate jokes, often at the expense of others) and uninhibited behavior are also frequently reported. In order to classify the disorder as good as possible, the division into stages of the social information processing system is used (perception, interpretation and response).

Disorders that occur within perception

After traumatic brain injury or in the case of Parkinson's disease, Huntington's disease or frontotemporal dementia, patients have more difficulty recognizing emotional facial expressions. In patients with autism spectrum disorder (ASD) or schizophrenia, impairments have been found in the recognition of emotions in facial expressions and voice (prosody).

Disorders that occur within interpretation

After observing socially relevant information, this information also has to be interpreted. In the interpretation process, a ToM must be formed by using knowledge from the social schemas (the schemas form a guideline for our social behavior). Some patient groups are less likely to have social schemes, such as patients with ASD: they have difficulty empathizing (Blair, 2003). Patients with various neurological disorders also have more difficulty in forming a ToM.

Disorders that occur in response

One's own behaviour have to be regulated during the reaction. Patients with brain injury often have difficulty understanding the social cues that indicate that they should change their behaviour (such as an angry look). They also frequently experience an inability to stop so that when they are able to absorb the social cues, they cannot inhibit their behavior yet.

Where is social cognition located?

The functions of the amygdala

One of the primary functions of the amygdala (located deep within the temporal lobe) is the automatic screening of information for social and affective relevance, primarily with regard to threats from the environment. The amygdala also plays a major role in forming and storing memories with emotional content. The amygdala is connected to the prefrontal cortex but also provides feedback to the visual areas (making the visual areas more active, for example, if a hazard is noted).

The function of the superior temporal sulcus

The superior temporal sulcus (STS) is mainly involved in the interpretation of socially relevant movement information (body posture, viewing direction, targeted movements and changes in facial expressions).

The function of the fusiform gyrus

The fusiform gyrus (in the occipital lobe and underside of the temporal lobe) includes the ability to process faces in detail (both the affective information and the static features for identification): 'fusiform face area'.

The function of the insula

The anterior part of the insula records and organizes internal physiological changes when affective information (both primary and secondary emotions) is perceived and understood.

The function of the striatum

The ventral part of the striatum predicts which reactions will lead to positive consequences. This area is regulated by levels of dopamine.

The function of the cortical mirror systems

The cortical mirror systems (demonstrated through shared neural activity in the parietal, premotor, somatosensory and motor cortex) are involved in mirroring the experiences of others in order to be able to imagine the experience of others.

The function of the prefrontal cortex

The amygdala and the striatum send their information to the VMPFC and the medial orbitofrontal cortex: both areas are continuously involved in updating the affective values ​​in variable situations. This emotion regulation takes place by always learning the associations between reactions and the affective consequences. Integrating complex information is also one of the tasks of the PFC (as mentioned earlier, the MPFC is involved in putting yourself in someone else's shoes).

The function of the cingulate gyrus

The cingulate gyrus is mainly involved in ‘conflict monitoring’, ‘reinforcement’ processes and ‘error detection’. For this reason, response selection and decision-making behavior are often regulated by the gyrus cinguli.

How is intelligence classified?

Two groups can be distinguished with regard to the classification of intelligence. On the one hand, intelligence is considered as one factor that predicts inter-individual differences and performance. On the other hand, intelligence is divided into different cognitive domains.

The g factor

Galton (1822) suggested that a smart person had a good neural network, while less smart people did have poorly functioning neural networks:  one characteristic of the nervous system was responsible for 'intelligence'. Spearman (1863), one of Galton's followers, concluded that there was a general factor the g factor. He believed that there was also a specific factor (s factor). Within this approach, there is one general intelligence that causes interindividual performance on cognitive tests. Spearman thought that the g factor included mental energy and that this factor was hereditary. Even today there are many people that support Galton. They based their own well-founded empirical theory on Galton's view, such as Jensen (2011) and Deary (2012).

Which theories divide intelligence into multiple factors?

Thurstone (1887) developed factor analysis and concluded that there are seven 'primary mental abilities': verbal comprehension, word fluency, number facility, spatial visualisation, associative memory, perceptual speed, and inductive reasoning. Gardner (1983) was strongly influenced by Thurstone. However, he did not believe in the g-factor and assumed that there are seven mental sources for information processing: each is used for a certain activity. His seven mental sources are a verbal-linguistic, logical-mathematical, spatial-visual, bodily-kinaesthetic, musical, interpersonal, and intrapersonal intelligence. Sternberg (contemporary) recognises the g-factor, but just like Spearman he assumes that there are also specific forms of intelligence: analytical, creative, and practical intelligence.

The core of the intelligence debate

The above-mentioned persons form the core of the intelligence debate: Galton and Spearman versus Thurstone, Gardner and Sternberg: is there one general g-factor or is it a collection of mental properties?

How is intelligence being measured?

The first intelligence test

Binet (1905) (together with Simon) was asked to develop a method that could be used to determine whether a child was or was not eligible for education. Binet developed several tests that were based on what children were expected to learn or to be able to achieve at school at different ages. Binet's test battery was translated into English and formed the 'Stanford-Binet Intelligence Scales'. Terman adjusted some test components in the intelligence quotient (IQ) by multiplying the ratio between chronological age and mental age by 100. Meanwhile, a lot of tests have been developed for both children and adults. Three of them will be discussed.

The Wechsler scales

Wechsler (1896) developed the 'Wechsler Adult Intelligence Scale' (WAIS). The latest version (2012) has fifteen subtests that are divided into verbal and performance subtests. The verbal subtests determine the verbal IQ, and the performance subtests determine the performance IQ. All raw subtest scores are converted to standard scores. There are four total index scores: verbal comprehension, processing speed, working memory, and perceptual reasoning. All four factors are strongly correlated, which highlights the fact that it is primarily the g factor that determines performance.

The difference between crystallised and fluid intelligence

Cattell (1943) introduced a crystallised form of intelligence (academic knowledge, such as vocabulary, general knowledge, and numeracy), and a fluid form of intelligence (abilities that can be used in novel problem situations). Crystallised intelligence hardly deteriorates as we age, whereas fluid intelligence is greatly affected by age. 

The Raven Progressive Matrices

Raven (1938) introduced the 'Raven progressive matrices' (RPM) as a test independent of cultural factors. According to Spearman it measures the g factor in the most unbiased way. The RPM is not a test battery. In the test Raven used a pattern in which a missing piece has to be chosen from among several alternatives. 

The National Adult Reading Test

The National Adult Reading Test (NART) is designed to estimate premorbid intelligence levels. It is a short test that measures vocabulary by asking the test subject to read out a list of 50 phonetically irregular words. The premorbid intelligence level can be estimated based on the test performance. The correlation with the verbal Wechsler IQ is strong (0.8).

The Flynn effect

The Flynn effect states that the average intelligence level increases by around five IQ points per year. This effect is universal, but not equally strong: the Flynn effect can vary from 5 to 25 points (Flynn, 1987).

How does intelligence work biologically?

The biological basis is the most determining factor of intelligence. Nowadays there is more and more supporting evidence for the notion that intelligence (the g factor) is mainly dependent on the functional characteristics of the connections between brain areas (and especially the connection between the parietal and frontal areas).

Is intelligence hereditary?

Jensen triggered the discussion about the heredity of intelligence in 1969 when he suggested that a genetic cause could explain the differences in the performance of whites and African-American children. According to him, there are two types of skills: learning / memory, and abstract reasoning. White and Asian children would perform better in the latter category. A great deal of research has been conducted into the relationship between intelligence and the speed of information processing (with reaction time RT as a measure in particular), which ties in with the existence of a g factor. According to Bouchard (2004), there is a very high heredity for the g factor (0.85). Also a large-scale study in Amsterdam that has been testing twins since 1977 states that intelligence is 80 to 90% genetic. The volumes of white and gray matter that are correlated to intelligence (0.25) are also genetically determined (Posthuma, 2003).

Where is intelligence located in the brain?

In higher-order animal species, the brains are larger in relation to the body, the weight is higher and the number of gyri and sulci is significantly higher. According to Toga and Thompson (2005) there is evidence of certain brain structures that are responsible for the heredity of the g factor. They emphasize the amount of gray matter in the frontal areas. According to Chiang and colleagues (2009), white-matter integrity is also related to IQ scores and is also highly hereditary. According to the neural efficiency hypothesis, more intelligent people have less activation for a particular task because they work more efficiently and therefore do not need more cells (Neubauer & Fink, 2009). Diffusion tensor imaging (DTI) measurement can be used to analyse how efficiently a signal is transmitted. Research by Tamnes and colleagues (2010) shows that DTI data of the left hemisphere is correlated with the verbal IQ and the performance IQ. The level of intelligence thus appears to be strongly correlated with the quality of the fiber pathways. 

What effect does brain injury have on intelligence?

In a study by Duval and colleagues (2008) participants (ranging from 0 to 84 years) were tested for intelligence after a single unilateral lesion. The Kennard principle did not seem to apply here: lesions at a younger age were associated with a lower IQ (while you would expect a higher IQ based on the high plasticity). According to Woolgar and colleagues (2010), lesions within the parietal-frontal network are related to low IQ scores on IQ tests that measure fluid intelligence. A study by Gläscher and colleagues (2010) suggest that intelligence (the g factor) is mainly determined by the connections that integrate working memory, visual-spatial, language, and executive processes.

To what extent is intelligence important in neuropsychological practice?

Why is the current level of importance?

The purpose of an intelligence test is usually to determine one's current abilities compared to peers. In neuropsychological assessment, determination of the patient's current capacities can be important because it provides a background against which performance on other neuropsychological tests can be compared. 

How are abnormalities being established?

An intelligence test is also used for the detection of functional disorders. However, doing this is difficult because the premorbid level is often unknown. This is done by an estimate based on age and gender. Another solution for this are hold tests: tests in which scores do not decrease with age and are also not susceptible to brain damage. Moreover, it is also conceivable that crystallized intelligence will be affected less quickly than fluid intelligence.

Are IQ tests valid in patients with brain damage?

Many IQ tests measure fluid intelligence, which is very sensitive to the effects of cognitive deterioration. The same problem is found with regard to the ideomotor or mental slowness that often occurs with different brain impairments. Using hold tests can solve this problem, but these too are not always valid.

What does a traumatic brain injury look like in clinical practice?

Traumatic brain injury (TBI) is the most common type of acquired brain injury (ABI) among people under 50 years of age. In this context, traumatic refers to violent: with mechanical force. If there is no (temporary) loss of consciousness after the impact, then we cannot speak of TBI: the severity and duration of this disorder provide an indication of the severity of the brain injury. Loss of memory is a major symptom of TBI. The retrograde amnesia (RA) immediately after the onset of consciousness diminishes over time. The patient is unable to remember the accident itself as well as a period of time preceding it. Patients also experience anterograde amnesia. Furthermore, a distinction can be made between the period of 'post-traumatic amnesia' (PTA), which is characterized by disturbed encoding and disorientation, and the loss of memory that occurs in the chronic phase. In addition to loss of memory, disorders in various domains may occur. 

How often does TBI occur?

About four percent of European patients who experience TBI die. The largest group of patients consists of young people aged 15-24 years. Most of the patients are victims of traffic accidents. Twice as many men as women suffer traumatic brain injury. 90% may return home after hospitalization; while ten percent are referred to a nursing home, a rehabilitation center, or a psychiatric hospital.

What is the neuropathology of TBI?

Primary damage

A distinction is made between ‘open’ craniocerebral injury (where objects or bone fragments penetrate the meninges, these injuries are commonly focally located) and the more frequent ‘closed’ cerebral brain injury. In the latter category, the damage is diffuse, often in the form of white matter injury (‘diffuse axonal injury’ or DAI): axons are damaged or torn off completely by the rotating forces. White matter injuries are usually combined with microhaemorrhages and ultimately axonal degeneration. These effects are most distinctive in the transitional areas between grey matter and the white matter connecting pathways, often in the deeper brain structures. If the violence impacts more linear than rotational, the moving skull suddenly makes contact with a hard surface, or the stationary skull is moved by a forceful blow, causing the brain to come into violent contact with the internal structures of the skull. This primarily results in damage to the grey matter (contusions). This is frequently found in the orbitofrontal and temporal brain regions. If the force is strong enough, a coup-contrecoup injury may result, where the location of cortical damage is diagonally opposite the location of the injury.

What does the secondary damage consist of?

The secondary damage is not caused by the forces that act on the skull, but by complications. These complications are intracranial or extracranial. With intracranial damage, complications such as swelling (oedema) or bleeding (haematoma) occur. Extracranial damage can disrupt the autoregulation. This may lead to shock, hypotension or hypoglycaemia, as a result of which the brain receives insufficient oxygen (hypoxia). Traumatic subarachnoid haemorrhage (TSAH) occurs regularly in moderate and severe brain injury combined with local bruises (contusions). TBI coupled with TSAH is usually associated with poorer and slower cognitive recovery. A general consequence of the secondary processes is increased intracranial pressure, causing secondary diffuse brain damage.

How are TBI patients diagnosed?

Some patients only experience a drop in consciousness; some go into a coma. For some patients, the coma will change to a temporary PTA, which means that the patient is unable to store new information for a certain period (ranging from hours to months). The duration of the PTA is the strongest indicator of the severity of the injury and a useful predictor of recovery (Brooks and colleagues, 1980). The PTA gradually disappears through 'islands of memory'. A minor injury: the patient has only been unconscious for a maximum of 15 minutes. This is the case in 80-85% of the cases. Severe injury: the patient has been unconscious for about an hour.

What are the neuropsychological consequences of a moderate to severe TBI?

Patients with moderate to severe brain injury almost always have permanent neuropsychological sequelae. Most disorders manifest themselves in the speed of information processing, attention and concentration, executive functions, and memory.

Is speed of information processing affected?

The most commonly reported complaint after brain injury is mental slowness (resulting in mental fatigue). This forms the core of most other disorders.

Is attention affected?

Within the focus area, it is especially difficult for patients to (1) focus attention when distracted, (2) divide one's attention between several tasks while under time pressure, and (3) sustain attention over time. For patients with moderate brain injury, this is explained by the mental slowness; for patients with serious brain injury, it is related to a primary attention disorder.

Are executive functions affected?

The frontal cortex is almost always affected by this TBI (both contusions and DAI), as a result of which the executive functions such as organising, planning, initiation, executing, control and evaluation of tasks are impaired.

Is memory affected?

Disorders within memory are already present in the acute phase. Learning can be disturbed, and the ability to retrieve information from memory is also impaired. But in fact, all aspects of memory can be affected following TBI.

Are language and speech affected?

The most common language problems are subtle problems in the areas of naming and word finding, verbal word fluency, and understanding of complex language. The classic aphasia syndromes rarely occur following TBI, but may develop after severe focal injuries in the left hemisphere. Dysarthria is slightly more common (after serious damage in the right hemisphere).

Is social cognition affected?

Most closely involved with the patient often report changes in behavior and emotions. For example that the patient exhibits disinhibited behavior, is more self-centered, no longer takes other people into consideration, cannot adapt their behaviour to the social situation, and is emotionally flat. This can be explained by the fact that he / she is no longer properly aware of social information due to social disorder and has difficulty creating ToM. They are bad at making decisions and stopping inappropriate behavior (even after negative feedback). The patient is often not aware of this.

What other complaints can be reported?

Other common complaints are emotional instability and a lower workload: the patient is tired, dizzy and irritated faster. PTSD symptoms are more often found in milder cases of brain injury. Emotional responses such as fear, feelings of depression, and decreased self-confidence may develop at a later stage, when the patient does develop insight into the consequences of the injury.

What are the neuropsychological consequences of mild TBI?

After mild TBI, the neuropsychological consequences (as mentioned in the case of moderate to severe injury) usually disappear within 3 months (Frencham, Fox & Maybery, 2005). The main complaints in the acute phase are within the domain of (working) memory, attention, and the speed of information processing. However, sometimes the symptoms persist and one speaks of a post-concussion syndrome or a post-concussion disorder. This is explained on the basis of a biopsychosocial model: the duration of PTA cannot predict these chronic complaints, while psychological factors (such as stress) are predictive.

The premorbid personality traits, and mood problems are strongly associated with the experience of cognitive complaints following mild TBI. Patients are subdivided into two groups: in one group patients think they have recovered well and they only notice the residual symptoms when they return to work (the connection with the brain injury that has been experienced is not always made), the second group is preoccupied with the possible serious consequences. The latter group experiences complaints that are excessive and not in proportion to the injury. They ultimately become stuck because of the increasing avoidance of cognitive load. A cogniform disorder (Delis & Wetter, 2007) is the term given to patients who report unlikely severe cognitive consequences due to their injury. These patients are most likely to blame brain injury for their long-lasting symptoms: this is not necessarily consciously. If there is a suspicion of a conscious thrust of the complaints or the simulation thereof, this is classified as "malingering". Symptom validity tasks and questionnaires about personality, mood and coping style are indispensable if a neuropsychological assessment is executed.

What is a whiplash?

'Whiplash-associated disorders' (WAD) arise after the patient is hit from behind in a car accident. The head first swings backwards (extension) and then flies forward (flexion). This is not a brain injury (because there is no absence of consciousness nor post-traumatic amnesia), but an injury to the neck. A whiplash is sometimes difficult to distinguish from mild brain injury due to the similarities in symptoms. 80% of whiplash patients recover within six weeks; the other patients experience persisting symptoms. The latter group suffers from a post-whiplash syndrome. They usually also have other symptoms such as mood disorders, visual disorders, concentration problems and many others. The differential diagnosis between post-whiplash syndrome and post-commotional syndrome is based on the presence of pain in the case of a whiplash.

How often does cancer occur?

50% of all men and almost 40% of all women develop cancer (often at a later age) (Kiemeney and colleagues, 2008). The treatment of tumours may involve surgery, radiotherapy, chemotherapy, hormonal treatment, immunotherapy, or a combination of these. 

What are intracranial tumours?

Intracranial tumours can be divided into two groups; primary and secondary tumours. A primary brain tumour originates from the brain tissue itself, the cerebral nerves, the pituitary gland, or the meninges. Almost always, low-grade tumours (particularly gliomas) develop into high-grade tumours in the long term. Secondary brain tumours are metastases from the primary tumour located elsewhere in the body: the cause of brain metastasis can be found in 3 out of 4 cases in lung cancer, breast cancer or skin cancer. In approximately 50% of the annually additional cases with a primary brain tumour there is a glioma. In this patient group, approximately 20% have a low-grade tumour: in half of the patients, the glioma does not grow within the first five years and patients can live for decades with a glioma without serious cognitive impairments. Patients with a high-grade tumour live on average just twelve months.

Cognitive impairments

The cognitive impairment and diaschisis (the phenomenon in which distant brain areas function less well due to damage to the connecting lines) in less well-functioning brain areas may be due to the tumor itself, a tumor recurrence, but also to treatment (such as neurosurgery and radiotherapy). A tumor-related epilepsy and the psychological state in which the patient finds himself can also be a trigger for the generation of disorders.

When is the brain tumor the cause of the cognitive impairments?

In the case of rare tumours, cognitive impairment is the most important characteristic; in tumours that occur more frequently, symptoms are often an increased intracranial pressure and loss of neurological function. In 8 out of 10 cases of a slow-growing tumor (such as low-grade gliomas), the epileptic seizure is the first symptom. In the case of fast-growing (high-grade) tumors there is more neurological failure and high intracranial pressure. The memory disorders and problems with the word fluency that are present before the operation are often attributed to oedema formation, a larger tumour and a higher tumour degree (Talacchi, Santini, Savazzi & Gerosa, 2011). A left hemispheric tumour causes more explicit disorders than a right hemispherical tumor. Glioma patients usually have more diffuse cognitive impairments. The glioma can generate a cortical reorganization due to the high plasticity of the brain: the function recovers (in part). A meningioma (tumour from the meninges or meninges) is benign in 90% of the cases. Through this space-consuming process, 30% of this patient group experiences severe cognitive impairments in the long term.

When is neurosurgery the cause of cognitive impairment?

Neurosurgeons are reluctant to operate on patients with tumours in brain areas that are crucial for cognitive functioning (often referred to as eloquent brain areas). In these cases an awake resection may be considered (tumour surgery performed while the patient is awake). Meanwhile, the neuropsychologist conducts cognitive tests. If a glioma is surgically removed, any focal cognitive disorders will disappear in the short term.

When is radiotherapy the cause of cognitive impairments?

The amount of radiation that can be administered without inducing serious consequences for the surrounding tissue (therapeutic index) limits the use of radiotherapy (radiation). An irreversible, serious complication is the late radiation damage that can occur even years after the radiation. This complication can manifest itself as local radiation necrosis (healthy brain tissue in a particular location dies) or diffuse encephalopathy (attention disorders, working memory disorders, psychomotor slowness accompanied by subcortical dementia, executive dysfunction, memory disorders and behavioral changes). More than 10% of patients whose skull was radiated suffer from a subcortical dementia profile. The chance of this developing is partly determined by the dose of radiotherapy (in Gray) and the size of the radiation area (skull base). For this reason, only focal radiotherapy is used in glioma patients.

What does a low-grade glioma patient look like?

In low-grade glioma patients, mild cognitive impairment often occurs. There is no progression in the disorders during the first few years. These disorders are not the result of late radiation damage or focal radiotherapy, but rather of the tumour itself or other treatment factors. The chance that these disorders do occur due to late radiation damage is if patients have previously had a skull base radiation, a high fraction dose or experienced radiation therapy ten years ago. According to Douw and colleagues (2009), all low-grade glioma patients who have been irradiated are cognitively deteriorating in the long term compared to non-irradiated patients who remain stable.

What does a high-grade glioma patient look like?

The cause of cognitive impairment is more difficult to discover in high-grade glioma patients because of the polytherapy consisting of radiation and chemotherapy. The rapid cognitive decline can usually be attributed to the progression of the tumour, especially if it has remained stable for a period (Bosma et al., 2007). Before the treatment, at least moderate cognitive impairment has often been found which points to the tumour as the main culprit.

Which treatments are available?

The most commonly used treatment for patients with brain metastases is radiation. Focal radiation is increasingly being used in connection with the increased risk of late radiation damage with skull radiation. A form of skull radiation that is unlikely to result in late radiation damage is prophylactic brain radiotherapy (used to prevent metastasis in patients with lung carcinomas). It even seems that this radiation positively influences functioning. Patients with a primary CNS lymphoma often have late radiation damage. Factors that contribute to this are a higher age, the need to use skull radiation, and the increasing use of medicines. Nowadays, this CNS lymphoma is treated more often with chemotherapy alone. Patients with nasopharyngeal tumours also have a greater risk of late radiation damage. Patients who had surgery for a meningioma several years ago often still have disorders in the domains: memory, language, motor control, and executive functions. A meningioma at the base of the skull is an indicator of poorer cognitive functioning than a meningioma at the upper edge. Radiotherapy has no cumulative effect on cognitive impairment after surgery.

When are drugs the cause of cognitive impairment?

Epilepsy is a possible side effect of the intracranial tumor. Anti-epileptics can also induce cognitive impairment. In successfully treated low-grade glioma patients, disorders in working memory capacity, executive functions, speed of information processing and psychomotor speed were related to anti-epileptics or epilepsy. The neurotoxicity of central nervous system medication is noticeable during treatment or shortly after treatment. The chemotherapeutic agents that are often written for glioma patients are often non-toxic and do not lead to cognitive impairments (such as lomustine). Corticosteroids are given to reduce intracranial pressure (by reducing oedema). The biggest disadvantage of this type is the chance of mood disorders and the chance of psychoses. Other cognitive impairments are often temporary.

What are extracranial tumors?

Complaints common in chemotherapy

Chemotherapy is also toxic to healthy cells, because there is no difference in the survival capacities for cancer cells and healthy cells. The side effects mainly concern nausea, hair loss, fewer white blood cells or platelets and sometimes this affects fertility and menstruation. The medication easily crosses the blood-brain barrier, causing neurotoxic effects in nearly 50% of patients. The most frequently heard complaints are forgetfulness, problems in sustained and divided attention and maintaining an overview. Even long after the treatment is stopped the medication can still cause (heart) problems.

Cognitive impairments occur

Due to methodological differences and the different types of chemotherapy, the studies estimate the incidence of cognitive impairment in breast cancer patients between 13 and 64%. These disorders most closely resemble a frontal subcortical image (there are problems in learning and retrieving information, working memory, executive functions, the complex aspects of attention and the slower pace of information processing). There is almost never a cortical syndrome (such as aphasia, apraxia or agnosia).

Is there a mood disorder and fatigue following cancer?

The location of the brain tumor influences the degree of anxiety and depressive feelings experienced. Such feelings are particularly strong after diagnosis, although the patient often adjusts quickly. 20 to 30% also have mood complaints in the long term. Fatigue is one of the most subjectively reported symptoms in both patients treated with chemotherapy and patients who have not undergone chemotherapy (such as patients with primary brain tumors).

What does Alzheimer's disease look like?

What is the prevalence?

Alzheimer's disease is the most common type of dementia. Progressive memory disorders are the most distinctive symptoms of this neurodegenerative disorder. The memory impairments gradually increase as the illness slowly creeps in. The diagnosis of dementia due to Alzheimer's disease is made if two or more cognitive domains are affected. Global cognitive deterioration is involved in a later stage of the disease. Neuropsychiatric symptoms such as depression, apathy, and anxiety also occur frequently. After the onset of the disease, a patient lives on average about seven to eight years. Prevalence will increase in the coming years due to two factors, collectively referred to as 'double aging': there are more elderly people who are getting older and older (the average life expectancy is increasing). As you get older, there is a high chance of developing Alzheimer's. Both the prevalence and the incidence double with every five years of life increase (0.8% in the 65-69 category; 28.5% in the 90+ category). However, dementia can also develop at an early age (before the age of sixty-five).

What are the risk factors?

The main risk factor is higher age. The second risk factor is being a woman. The third risk factor is related to genetic predisposition, although the non-familial (sporadic) form is more common.

What does Alzheimer's disease look like clinically?

The diagnosis of Alzheimer's disease is made “per exclusionem”: if all other causes of cognitive decline are excluded, this diagnosis remains. A more inclusive approach is discussed later. First, the severity of the symptoms is determined (syndrome diagnosis); is dementia present or not? If this is found to be the case, the next question concerns the type of dementia that is present (etiological diagnosis). The NIA-AA criteria make a distinction between a low, medium or high probability to underlying Alzheimer pathology. A definite diagnosis can be made post-mortem when the neuropathological characteristics of Alzheimer's disease have been demonstrated during an autopsy or when a genetic mutation is present. In the DSM-5, a distinction is made between extensive neurocognitive disorder (dementia) and minor neurocognitive disorder (mild cognitive impairment).

What is a mild cognitive impairment?

Sometimes the development of dementia is preceded by 'mild cognitive impairment' (MCI). In the case of 'amnestic MCI' there are disorders within episodic memory; in a 'non-amnestic MCI' the impairments are found in a different domain. If there are impairments in multiple domains, this is referred to as an 'MCI in various domains'. The risk of developing Alzheimer's disease seems to be highest in patients with the amnestic type of MCI. Dementia develops in 10-15% of patients with MCI within the first five years. However, many patients remain stable or even recover.

What is Alzheimer's neuropathology?

Plaques and tangles

Alzheimer's neuropathology covers senile plaques (accumulations of the amyloid beta-protein between brain cells) and neurofibrillary tangles (entanglements of the tau protein in brain cells). Both induce cell death and atrophy (shrinkage) of the brain.

Amyloid cascade hypothesis

The amyloid-cascade hypothesis (AC hypothesis) is the best known hypothesis about the pathogenesis of Alzheimer. This hypothesis assumes that the first step in the development of Alzheimer's disease is the abnormal cleavage of the APP. This creates an imbalance between the production and breakdown of amyloid beta protein, as a result of which this protein starts to aggregate and form plaques. At a later stage the tangles of the tau protein are added: the tau proteins correlate strongly with the severity of dementia. There is no medicine yet.

Vascular hypothesis

Many Alzheimer's patients have mixed pathology: they have the neuropathological characteristics of Alzheimer's but also have cerebrovascular damage. Younger patients more often have the pure form of Alzheimer's disease. The vascular hypothesis states that vascular damage contributes to Alzheimer's disease, and is an addition to the AC hypothesis.

What is the neuropsychological picture of Alzheimer's disease?

How is the disease diagnosed?

A clinical interview with someone who knows the person with suspected dementia well is very important in diagnosing Alzheimer's disease. The first impression of cognitive functioning is made using the MMSE (Mini-Mental State Examination). 

What are the neuropsychological symptoms?

The best known symptom is having memory problems. The gradual increase in memory impairments is caused by the atrophy of the medial temporal lobe (which also includes the hippocampus). The pattern in which a patient goes from cognitive decline in two domains to a general cognitive decline varies per person. During the initial phase there often is an anterograde episodic memory disorder. Retrograde memory impairment develops in a later stage. Impairments in sense of orientation and language are also common in the initial stage of the illness. Shortages in executive functioning (attention and cognitive flexibility) occur when the disease develops, and get worse as the disease progresses and the tasks become more complex. Apraxia and visual-perceptual (both visual-spatial perception and visual shape and object recognition) disorders can also occur.

What types of dementia are there?

With Alzheimer's disease, memory problems are most prominent; this is less the case in dementia with Lewy bodies. Impairments in language are the core symptom of semantic dementia and primary progressive aphasia. Slowness and decreased mental flexibility are mainly associated with vascular dementia. The division between cortical dementia or subcortical dementia is no longer made because the symptoms do not adhere to such neuroanatomical substrates.

Can Alzheimer's disease be seen as a single entity?

Alzheimer's disease has a typical and atypical course. In the typical course memory impairments are the prominent feature; the atypical variant often reveals at an early age (around 55) and is characterized by language or visual-spatial disorders. Alzheimer's is more progressive in younger patients (van der Vlies and colleagues, 2009). 'Posterior cortical atrophy' (PCA) is the visual form of Alzheimer's (visual dysfunctions but memory and executive functions are intact).

Neuropsychiatric symptoms

Behavioral changes and changes in mental state are among the neuropsychiatric symptoms. These symptoms are very common in dementia patients, but often decrease in the long term due to reduced anosognosia.

What changes occur in the brain?

Diagnosis of Alzheimer's disease is completely dependent on clinical manifestations, but neuroimaging using either CT or MRI is often part of the diagnostic work-up. An atrophy of the medial temporal lobe (and therefore the hippocampus) is a feature consistent with Alzheimer's. The degree of atrophy is determined on the basis of Scheltens visual rating scale (this is a five-point scale, a score of 2 or more indicates atrophy). General atrophy occurs at a later stage. In young patients, atrophy is limited primarily in the parietal areas. Often there is also damage to the small vessels in the form of microbleeds, lacunar infarcts (small infarcts in the areas of the smaller blood vessels in the deeper tissues) and whit matter anomalies. EEGs have shown that Alzheimer's patients often have a diffusely delayed EEG: more slow waves and less fast waves. A specific PET scan has shown that the temporo-parietal areas are less active compared to healthy controls. A new type of PET is amyloid PET: for the first time it is possible to visualize the accumulation of amyloid beta in a living subject.

Treatment with cholinesterase inhibitors

Cholinesterase inhibitors are prescribed to reduce symptoms in mild to moderate Alzheimer's disease. The cholinesterase inhibitors ensure that acetylcholine is broken down less quickly and therefore stays in the synapse longer. If the disease stabilises for six months, the treatment has been successful. The effect is therefore small and there are annoying everyday side effects such as diarrhea and nausea.

How is Parkinsonism defined?

Parkinsonism, also known as hypokinetic-rigid syndrome, is a collection of motor symptoms that form the core symptom for a group of progressive neurodegenerative disorders classified as the 'Parkinson spectrum'. Parkinson's disease is the most common disorder in the Parkinson spectrum. Other forms, such as dementia with Lewy bodies (DLB) are less common. Secondary symptoms of Parkinson's disease may also arise as a result of vascular damage: vascular parkinsonism. In contrast to vascular parkinsonism, Parkinson's disease is more progressive, no to little response to specific medication (although patients with vascular parkinsonism often do not respond to this), cognitive decline in the initial phase and a shorter lifespan. This chapter only deals with Parkinson's disease.

What is the clinical picture?

Motor symptoms

According to Wolters (2007), the motor symptoms of Parkinson's disease have four characteristics:

1. Lack of movement/slowness (akinesia, hypokinesia and bradykinesia).

2. Rigidity (movements are stiff and sometimes jerky; 'cogwheel phenomenon').

3. Rest tremor.

4. Postural instability.

Non-motor symptoms

Although there are often more non-motor symptoms, they are usually experienced as secondary. This mainly concerns fatigue, hyposmia (disturbed sense of smell), autonomic disorders, sleep disorders, affective disorders, apathy, cognitive impairment, impulse control disorders, and psychoses and hallucinations. 75% of all patients suffer from pain, which may be caused by muscle spasms or dystonia (persistent muscle contractions): the pain often diminishes once treatment with anti-Parkinson's drugs is started. Autonomic impairments such as blood pressure fluctuations, excessive perspiration, constipation, bladder problems and sexual difficulties occur. Some Parkinson's patients suffer from a sleep disorder (especially sleeping and staying asleep is experienced as difficult). Some suffer from 'REM sleep behaviour disorder' (RSBD): a specific sleep problem characterized abnormal REM sleep. The content of dreams is often extremely vivid, with fearful and aggressive themes: for this reason many couples go to sleep separately because otherwise they can regularly expect an unintended thump or kick.

What are the diagnostic criteria?

Because of the initially non-specific symptoms, the course of the symptoms is an important part of the diagnosis. The brain abnormalities can only be seen at an advanced stage, but the MRI can provide a definitive answer to a vascular disorder or tumors at an early stage. A PET and SPECT scan do not benefit from the differential diagnosis. There must be bradykinesia with one of the following: rigidity, postural instability and / or rest tremor. The motor symptoms should subside after taking antiparkinsonian medication (levodopa). Dementia with Lewy bodies (DLB) is more likely when there have been visual hallucinations in the year that the motor symptoms began. An atypical form of Parkinson's disease is considered if serious autonomic, eye movement or balance disorders are present at an early stage. Within Parkinson's disease there are subtypes such as the balance subtype, tremordominant and hypokinetic-rigid subtype. Each subtype has a different course and treatment. When the symptoms start on the left side of the body, there are often more cognitive problems (Katzen, Levin & Weiner, 2006).

Who develop Parkinson's disease?

Women have a slightly greater chance of developing Parkinson's disease. A higher age is a major risk factor. Every year 8,000 people are diagnosed. The Unified Parkinson Disease Rating Scale (UPDRS) is a multidimensional scale to estimate the severity of Parkinson's disease. This scale consists of six sections, two of which provide insight into the severity: section three (motor symptoms) and section five (the Hoehn & Yahr scale with five stages of severity ranging from symptoms on one side of the body to a severely disabled condition).

What causes Parkinson's disease?

The cause of parkinsonism is the degeneration of dopamine-producing neurons in the compact part (part of the substantia nigra or SN), first in the dorsal striatum and later in the ventral striatum and the mesocorticolimbic dopamine system. The SN is part of the basal ganglia, which interact with the thalamus and the cortex. Reduced dopamine disrupts this entire circuit: in the end, the subthalamic nucleus (STN) becomes hyperactive and causes decreased activation of the motor cortex via the thalamus. As soon as half of the dopamine-producing neurons in the SN have disappeared, the Parkinsonian symptoms begin. Changes within the cholinergic, noradrenergic and serotoninergic systems are also present.

Can Parkinson's disease be treated?

There is currently no treatment to cure Parkinson's disease and the deterioration cannot be slowed down. The antiparkinsonian medication, in particular levodopa and dopamine agonists, suppress motor symptoms. For the remaining symptoms, muscle relaxants and pain medication can be administered (Lohle and colleagues, 2009). Side effects of the antiparkinsonian medication are confusion, delusions, sleep attacks or even a psychosis. Motor side effects are also common over time: in the beginning there is tolerance (which results in a 'wearing off' or 'delayed response' of the medication). Dyskinesias (over-mobility) especially increase when the dose of levodopa is highest. The dopamine agonists cause impulse control problems. Attention and memory disorders, hallucinations and even dementia can be the result of anticholinergic drugs. If the medication is no longer effective, or if the side effects can no longer be tolerated, a brain operation may be considered. In this operation an electrode is implanted in the brain for continuous stimulation ('deep brain stimulation' or DBS), usually in the STN. The battery of the electrode is placed in the chest or abdominal cavity. Eventually, paramedical care (in the form of a multidisciplinary team) is always necessary for the patient to function as independently as possible.

Which cognitive impairments occur?

The majority of patients develop cognitive impairments. During the course of the disease these impairments may gradually develop into dementia. The cognitive impairments are noticeable in attention, mental speed, and memory, as well as in visuospatial deficiencies later in the course of the disease.

What does dementia look like in patients with Parkinson's disease?

Most patients with Parkinson's disease eventually develop dementia. In this case cognitive deterioration is most prominent in the areas of attention and speed. Executive impairments are prominent. Memory is not necessarily impaired (forgetfulness is reported often). Memory problems in patients with Parkinson's disease are less severe than in Alzheimer's disease. In addition, the memory disorders in Parkinson's patients mainly relate to retrieval of information. Another difference is that visual hallucinations are more common in Parkinson's disease patients (even without medication).

What makes Parkinson's disease even more difficult for patients?

Due to the disruption of the dopaminergic frontostriatal circuit, there are mainly problems within the executive functions. Impairments in memory, attention, and visual-spatial functions, and problems in the mental information processing speed. The visual-spatial defects are often secondary to the attention problems. Patients also have difficulty with cognitive flexibility and manipulating information in the working memory. They have a reduced capacity for initiative, increased introversion and less need for change. Levodopa has a positive influence on cognitive flexibility but induces problems within implicit learning as well as impulsive behavior. Patients have difficulty with the internal generation of automatisms: for this reason learning new skills is often disturbed because there is no transition from conscious to unconscious behavior. At a later stage, patients also have difficulty forming a ToM because they can no longer properly process emotional information based on negative emotions and facial expressions. Language problems are rare (there are subtle problems within the complex grammar), but speech problems are common. Sleep disorders increase the chance of developing dementia and a higher debut age and so-called ‘axial’ symptoms increase the chance of cognitive impairment (Wolter & Bosboom, 2007; Muslimovi and colleagues, 2009).

Which mood and behavioral disorders occur?

The amount of dopamine in the brain is related to (common) complaints of anxiety, depression and loss of motivation. The most common depressive symptoms are anhedonia and a depressed mood. In most cases the severity of the depression is mild to moderate. Medication often has a positive influence on these complaints. The psychotic behavior comes at an advanced stage and expresses itself by delusions and visual hallucinations. Initially, the hallucinations are even friendly and patients are fully aware of it. Later the content becomes more threatening and the insight disappears. This is often the reason for admission to a nursing home. The medication and DBS of the STN can lead to impulse control disorders (ICDs), 'punding' (an abnormal fascination and preoccupation with irrelevant activities) and a levodopa addiction. ICDs express themselves in being unable to postpone rewards, less inhibiting control and not having an overview of the consequences of behavior. Common ICDs are pathological gambling and hypersexuality. Punding can express itself, for example, in the urge to clean: the basic needs and social responsibilities are ignored as much as possible.

How can multiple sclerosis be defined?

Multiple sclerosis (MS) is a fluctuating, chronic central nervous system (CNS) disorder characterized by progressive multifocal demyelination and inflammation of the white matter (Kuks & Pike, 2007). It usually develops between the age of 20 and 40 years, and it is the most common neurological disorder in young adults.

What is the clinical picture?

The inflammation of the white matter mainly occurs in the optic nerve, brainstem, spinal cord and cerebellum. The first characteristics are sensitivity problems and temporary vision problems such as optic neuritis (inflammation of the optic nerve: in a third of patients this is the first symptom of MS). Loss of strength, speech disorders, sexual dysfunctions, pain, fatigue, bladder disorders and disturbed coordination are other common complaints. In addition, there will also be neuropsychiatric and cognitive characteristics. The Uthoff phenomenon is that some patients experience more symptoms when it gets warmer. With a scale known as EDSS, a neurologist can map the severity of the neurological deficits.

How is the disease progressing?

Three subtypes of MS can be distinguished:

1. Relapsing-remitting MS (RRMS): 70-80% of patients have this subtype, which is characterised by periods of recurrence (exacerbations or relapses) alternating with periods of remission in which the patient is almost free of symptoms. 

2. Secondary progressive MS (SPMS): three-quarters of the RRMS patients develop the SPMS after a few years: there is progressive decline with almost no remission.

3. Primary progressive MS (PPMS): this variant affects 10-20% of MS patients. There is a continuous progression of the symptoms right from the beginning.

The course is unpredictable and a distinction is often made between a benign MS and a malignant form of MS. Premorbid life expectancy is only a few years away.

What are the diagnostic criteria?

The clinical picture is very heterogeneous and the course is very variable. The diagnosis is dependent on the occurrence of at least two periods of clinical manifestations and multiple white matter lesions in the CNS made visible by MRI (McDonald and colleagues, 2001). The MRI also showed that 9 out of 10 patients also have abnormalities of the cerebral fluid. The diagnosis is facilitated by MRI scans, but sometimes it can take a long time before a definitive diagnosis is made (the symptoms are then grouped under the term 'possible MS'). The prevalence is higher in cold countries compared to subtropical countries. The male to female ratio is 3: 1.

Can MS be treated?

Treatment consists of the administration of a single high concentration of corticosteroids, which alleviate clinical symptoms. It cannot be given continuously in a low dose due to the many side effects. There are many medicines on the market that prevent exacerbations by around 30-40% annually. The following also applies here: optimal care is multidisciplinary care.

What causes MS?

MS is seen as an autoimmune disease with a genetic (familial) component that is triggered by exogenous factors. The universal differences suggest an important role of the environment: as mentioned earlier, the prevalence increases as the distance to the equator increases. This can possibly be explained by the lack of sunlight and vitamin D. According to the inflammatory hypothesis, immunological factors make a major contribution to pathogenesis: the exacerbation causes an inflammatory reaction whereby T lymphocytes pass through the blood-brain barrier and attack the myelin. Proteins in the cerebral fluid also indicate an inflammatory response and thus the breakdown of myelin sheaths. In addition to demyelination, there is also (axonal and neuronal) degeneration or global atrophy. This is demonstrated by post-mortem studies which also show that the ventricles are often dilated and the cortex is 30% less thick. This means that MS is no longer just a white matter disorder.

Which cognitive impairments are there?

Only 5-10% of MS patients develop dementia. The motor and / or visual limitations can have an influence on the performance subtests, so that there is a possible IQ decrease. The cognitive disorders are often subtle. In most cases the memory and the speed of information processing are affected. The PASAT is a very sensitive multimodal test (unfortunately not really specific) that can mainly map the capacity of information processing but can also map other impairments. Simple attention tasks are not a problem for MS patients; the specific functions (such as focusing attention, maintaining or dividing) are often affected. It is unclear whether there is a problem of attention or whether it is caused by the slow speed of processing information. The most frequently reported memory problem concerns the deepening of information, but there is a global pattern; memory deficits in auditory and visual modality. The recognition is intact (Zakanis, 2000). In addition to the two core deficits, there are often also mild disorders in executive functions, emotion perception and ToM. Language disorders are very rare as well as agnosias.

Is there a relationship between the severity of cognitive impairment and the severity of MS?

Surprisingly, there is no strong relationship between the severity of cognitive impairment and the severity of MS. The amount of cortical atrophy (especially in subcortical structures) and the width of the third ventricle predicts cognitive functioning better than the white matter lesions. The cognitive impairment is worse with PPMS and SPMS compared to RRMS. The prognosis is worse if the disorders are already present at an early stage. Patients with SPMS have worse cognitive performance within the subtypes with a progressive course (PPMS and SPMS) (Chiaravaloti & DeLuca, 2008). As mentioned earlier, memory disorders are at the forefront of RRMS and deficits in the executive functions are at the forefront of SPMS and PPMS. All research findings are based on research on MS patients whose disease was not currently active: due to ethical and methodological reasons, patients with an exacerbation are excluded from the study. The only study that did examine such patients concluded that attention disorders during such a relapse are related to transient inflammatory changes.

Are emotional disorders common in MS?

The prevalence of anxiety disorders, psychotic disorders and bipolar disorders is higher in MS patients than in the normal population (Feinstein, 1999). 27-54% suffer from depression. Suicide is responsible for 15% of deaths in MS. So-called forced laughter and compulsive crying are also common. The only complaint that occurs more often than the depressive complaint is fatigue. 92% of MS patients characterize fatigue as the most restrictive syndrome. There is no cure for fatigue yet.

Which syndromes exist?

Depression

A depression manifests itself on both psychological and physical level. The depressive mood and / or anhedonia (not being able to experience pleasure) and / or loss of interest are the main characteristics that will cause the patient to neglect himself and the environment. The above-mentioned symptoms must be present for at least two weeks combined with at least four of the following: feelings of guilt, continuous thoughts of death, feelings of inferiority, anxiety, tiredness, loss of energy. Changes in appetite and body weight, sleeping problems, psychomotor agitation or inhibition, and a decreased libido may also occur. Frequently mentioned cognitive problems are related to the ability to think, focus attention, and making decisions. The physical symptoms have no physical cause.

Mania

A mania is the emotional opposite of depression. There is a continuous and abnormally elevated (euphoric), uncontrolled and excited (expansive), or irritable mood, and the mood change must be accompanied by persistently increased activity or energy levels. Symptoms such as inflated self-esteem, excessive optimism, or grandiosity may also occur. Speech is often accelerated and psychotic symptoms occur regularly. The libido increases as well as the energy. Sleep is suddenly no longer important. A distinction is made between a manic episode (at least a week or less than a week when hospitalization is necessary) and a hypomanic period (the manic symptoms are less severe).

The difference between unipolar depression and bipolar disorder

One in seven people develop a depressive or unipolar disorder, usually between the ages of 25 and 40 years. Women are twice as likely to develop depression as men. On average, depression lasts for eight months but four in ten patients experience a relapse after recovery. The bipolar (manic-depressive) I disorder (depression and mania) is just as common among men as it is among women; the bipolar II disorder (depression and hypomania) is more common in women. Both disorders usually starts in early adulthood and is lifelong.

The dimensional approach entail

In the DSM a clear distinction is made between depression and (hypo)mania, while the more and more scientists are arguing for a dimensional treatment, where both are on one continuum.

What does depression do to the body?

Depression is the result of a heterogeneous aetiology. Changes occur in the stress response system, monoamine system and immune system. Bipolar disorder also has such a heterogeneous aetiology.

Which cognitive impairments are there?

Earlier in this chapter, the majority of clinical issues have already been listed. The cognitive disturbances are partly secondary to this problem. The main disorders in depression are within the domain of psychomotor speed, sustained and selective attention, executive functioning and declarative memory. In the case of a depressive episode, the disorders in executive functioning and attention are in the foreground; in the case of chronic depression, memory problems are especially important. The symptoms of a manic syndrome are distractibility, increased risk-taking, and an increase in goal-oriented activities. The cognitive impairments that are part of a mania are experienced as more serious, more complex and more variable than the impairments in depression. The executive disorders are also more prominent in a mania. In the case of a depressive and bipolar disorder, there appears to be a global disruption of information processing. For example, in some patients, conscious and controlled information processing is impaired. The accompanying cognitive effort hypothesis states that the reduced performance on neuropsychological tasks can be explained by the lack of controlled information processing. However, the hypothesis does not explain the reduced performance on attention tasks. The second possible explanation for the reduced performance on cognitive tasks lies in the response at making a mistake: once depressed patients realize that they have made a mistake, they will make mistakes faster than healthy controls. A third explanation lies in a lack of motivation.

Cognitive impairment

As soon as the mood disorders disappear, most cognitive impairments also resolve. In this case, the severity of these state-related cognitive impairments is correlated with disease factors such as the number of episodes and the duration of the disease. However, sometimes these disorders persist even when the disease is not present (during symptom-free, euthymic periods), making them a 'trait' characteristic. The cognitive symptoms of bipolar patients in particular often persist when the disorder is not present (in particular the speed of information, executive control, fluency and working memory).

Demographic factors

Cognitive impairments are often more severe in elderly people with a depressive or bipolar disorder than in younger patients. The precise cause of cognitive impairment in mood disorders is still unclear, but it is certain that there is a complex interaction between environmental, genetic, developmental neurological and neurodegenerative factors.

What are cognitive side effects caused by treatment?

The side effects of medication

Lithium is a mood stabilizer, and is the first choice of medication in bipolar patients. Lithium can also be prescribed for patients with therapy-resistant unipolar depression. Some studies argue that lithium causes (severe) cognitive complaints. On the other hand, there are a lot of studies that report positive effects of lithium in the long term. This discrepancy is central to the current discussion about the neuroprotective versus the neurotoxic effects of lithium (Fountoulakis and colleagues, 2008). All possible side effects are reversible once the medication is stopped. Benzodiazepines have a negative effect on the speed of information processing, memory and attention. For depression, an SSRI (selective serotonin reuptake inhibitor) is the most prescribed drug and would not involve any negative cognitive risks.

The side effects of electroconvulsive therapy

In the case of a severe medication-resistant depression or mania, electroconvulsive therapy (ECT) can be chosen. ECT is the best method of treatment for depression, even better than SSRIs. However, due to the negative / somewhat frightening atmosphere about "electroshock therapy" and the possible cognitive side effects, there is a high threshold for application. The most common cognitive side effect is memory impairment: both anterograde and retrograde amnesia can occur. The anterograde amnesia is transient and disappears within a month; the retrograde amnesia (especially for recent events up to three months before treatment) remains longer.

Which cognitive biases are involved?

Mood biases

Because of a bias in information processing, there is a preference for processing negative (mood-congruent) information. Sometimes this bias is permanent. Teasdale's differential activation hypothesis (1988) states that patients with a history of depression can relapse more easily: a slight drop in mood can reactivate latent negative self-schemas because they have been linked to the depressed mood during an earlier episode of depression. A cognitive bias in unipolar depression can be found in various cognitive domains, in particular in attention and memory. Not much research has been done into a bias in bipolar patients, but it seems that there is indeed a positive equivalent of the attention bias just mentioned. In addition to a bias in information processing and attention, there is also a bias in explicit memory: mood-related information is processed more extensively, and this information is frequently associated with other information so that memories for such stimuli become stronger. A bias in implicit memory has not been demonstrated yet.

Which bias plays a role in social cognition?

The 'attributional style' is the extent to which people attribute events to an external cause or to themselves. This style is another form of bias. In depressive patients a negative attributional style is often found (the negative events are caused by themselves while the positive events have an external cause), and in manic patients a positive attributional style is found. Patients with bipolar disorder also have a disorder in ToM and the recognition of emotions in others. These disorders within social cognition remain present in euthymic episodes of bipolar patients.

What does neuroimaging show?

The processes involved in emotion regulation are dependent on and shaped by the ventral and dorsal areas of the brain. The ventral system includes eight areas of the brain: the amygdala, insula, VLPFC, OFPFC, the ventral ACG, the ventral striatum, the thalamus and brain stem. This system plays an important role in the interpretation of emotional meaning and the production of states of mind. The dorsal system comprises four regions: the DLPFC, DMPFC, the dorsal ACG and the hippocampus. This system is mainly involved in the regulation of mood. A bipolar state of mind may be due to a dysfunction in inducing and controlling a state of mind; A depressed state of mind seems mainly to be a dysfunction in the control of the emotional response.

What does structural imaging show?

In bipolar patients there are changes in temporal lobe volume, reduced prefrontal volume and, on the contrary, the amygdala is larger (Keener & Phillips, 2007). These areas may be the top-down cause for the changes in emotion regulation as described above. Furthermore, there is also less volume in the DLPFC and ventral PFC that both. Especially the latter is related to modulating mood, based on integrated cognitive and emotional information. In both a depressed patient and a bipolar patient, there are more white matter hyperintensities. These are most common in bipolar I disorder followed by bipolar II disorder and eventually unipolar depression. The volume of the hippocampus is also smaller in a depressed patient. There is also atrophy in the OFC, ACC, the putamen, nucleus caudatus, and the amygdala. This data has no diagnostic value and does not necessarily have to be present.

What does functional imaging show?

Multiple parts of the PFC show a reduced activity (hypofrontality) in bipolar patients, which causes disturbances in executive functions, also in euthymic periods (trait). The hypofrontality of the DLPFC is found in the depressive and manic periods; the hypofrontality of the medial frontal cortex and the ACC are overactive during mania but underactive during depression. There is also a continuous increase in limbic activity. This dysfunctional circuit between the prefrontal and subcortical areas is probably the cause of bipolar disorder. In patients with depression there is an increased metabolism in the ventral limbic areas, amygdala and thalamus. This higher metabolism is positively related to the severity of the depression. The overactivity in the areas associated with the memory is probably responsible for the memory bias.

Where does the term psychopathy come from?

Psychopathy is a term that dates from the early nineteenth century. Pinel introduced the term and used it for patients who behaved violently and inadequately. Since the 1940s, the term ‘psychopathy’ includes a certain combination of socially abnormal behavior and personality traits.

What are the clinical picture and diagnostic criteria of psychopathy?

In particular, much attention and research is paid to criminal psychopaths (such as serial killers and rapists), while there are also many non-criminal psychopaths. According to Lombroso (1867), a psychopath or criminal can be recognized by facial features such as wide jaws and deep-set eyes. In 1991 the PCL (‘Psychopathy Checklist’) was developed with which the degree of psychopathy can be reliably determined in prisoners and forensic patients. The PPI (‘Psychopathic Personality Inventory’) is used in the normal population. Psychopathy is a severe and difficult form of antisocial personality disorder (ASP), and is characterised by insensitivity, coldness, lack of empathy, pathological lying, and manipulation. Not everyone with an ASP develops into a psychopath. A precursor to psychopathy in childhood is conduct disorder.

How often does it occur?

The prevalence in the healthy population is estimated at 1-4%. 15-30% of the international patients are diagnosed with psychopathy (Hart, Hare & Forth, 1994). All these studies have only been performed on men. Women often score lower, partly due to the masculine description of the character traits. 

What are the aetiology and neuropathology of psychopathy?

The Low Fear Model

There is a specific number of neurocognitive limitations in psychopathy. Deviations have been found in the attention processes, forms of learning forms, emotion processing, and recognition of emotions (fear and sadness are less well recognized). The amygdala plays a central role.

The 'Low Fear Model' (LFM) is based on the abnormal (reduced) anxiety responses of psychopaths. Psychopaths do not have a normal anxiety response and coordinate their behavior less as a result of negative feedback (such as a prison sentence). They display the punished behaviours several times. Two criticisms of this model are:

1. Moral socialisation is taught not only by a conditioned fear response.

2. Psychopaths do not always display such a fear response to punishment.

The Response Modulation Hypothesis

The 'Response Modulation Hypothesis' (RMH) from Harpur and Hare (1990) assumes that peripheral stimuli (which do not receive immediate attention) are not properly processed. Response modulation is a rapid and relatively automatic shift in attention (away from the object of focus) that allows people to monitor peripheral information and actively use it if necessary. Psychopaths do not make this shift and consequently fail to adequately calculate the consequences of their behaviour and cannot use this information to adapt their behaviour. All clinical manifestations, including increased impulsiveness, are an expression of the failing integration of peripheral information. A shortcoming of this hypothesis is that empirical research has shown that psychopaths can indeed make this shift.

The Violence Inhibition Model

Following the criticism of the aforementioned attention model, Blair and colleagues (2005) developed the 'Violence Inhibition Model' (VIM). According to this model, everyone has a 'Basal Threat System' in the brain stem that is automatically activated by 'distress cues such as grief and anxiety. This system enables us to react to the pain of others and to learn that it is unacceptable to display behaviour that causes harm to others. As a result, we develop a 'violence inhibition' mechanism. Psychopaths have a disorder in this system. A shortcoming of this model concerns the notion that it cannot explain the emotional and attention disturbances that can be explained by the LFM and RMH.

What is the integrated emotion system?

The Integrated Emotion System (IES) model is an integration of the LFM and VIM (Blair and colleagues, 2005). The model consists of five systems:

1. The first system concerns in the transfer of sensory representations.

2. The second system plays a major role in making quick decisions based on the expected reward or punishment ('valence representation'). These valence representations are disturbed in people with psychopathy.

3. The third concerns motor responses and is also affected by input in the shape of valence representations.

4. The fourth system, the response selection system represents the expected reward or punishment associated with a stimulus, and possibly also with the response to that stimulus. The stimulus that yields the largest possible reward is selected as quickly as possible.

5. The fifth system is the 'response-gating' system that becomes active as soon as an expected reward pattern or punishment pattern is violated. This system changes the stimulus-response associations and increases or decreases the chance of displaying the same behaviour in the future.

The amygdala plays the largest role in this model. This model explains why aversive conditioning is not available for psychopaths. In conclusion, it can be said that two models assume a primary affective problem (the IES and the LFM) and one assumes a primary attention problem (RMH). Both affective models emphasize the importance of the amygdala. The difference between these two models is that the IES is more broadly applicable and the LFM mainly looks specifically at the insensitivity to punishment and sensation seeking.

What do neuroimaging techniques show?

The differences in neuroimaging data from all studies are difficult to compare due to the following reasons:

• The definition of the concept of psychopathy may differ markedly for each study.

• The collection, processing and analysis of data differs per study.

• There are only a few studies in which there is no comorbidity, drug use, or medication use and psychopathy is determined using the PCL-R.

• There is no consensus about the perfect control group yet.

• There is still no consensus about the correct cut-off score of the PCL-R.

The limited data available suggests structural deviations in the prefrontal-temporo-limbic structures (which are involved with affective information processing and learning processes). More specifically, a smaller prefrontal volume of the gray matter, the amygdala, the posterior hippocampal regions and the superior temporal gyrus. The corpus callosum has a slightly larger volume. The functional imaging studies suggest a lower metabolism and reduced fluid administration ('perfusion') in both temporal and frontal lobes. Recent studies into the electrophysiological processes involved in learning have shown that psychopaths have smaller ERNs ('error-related negativities'): this ERN occurs at the first signs of error detection. In addition, this (weak) signal is not used optimally.

What behavioral and cognitive impairments are there?

Remarkably, people often associate psychopathy with low SES and low intelligence, but objective research shows no correlation between these (Blair and colleagues, 2005). It seems that a higher intelligence is related to the earlier taking of criminal actions. In this case, the higher intelligence, in contrast to the normal population, is not an inhibitory factor for problem behaviour. The cognitive impairments are mainly limited to attention, learning, decision-making, and social cognition.

What role does attention play?

As the RMH model had already pointed out, deviations in the shift of attention to non-dominant stimuli are affected. Multiple studies have not been able to replicate this. The attention function would only fail in some situations, such as affective situations, due to a dysfunctional amygdala.

What are the disorders in learning and decision making?

Learning and decision-making based on punishment and reward have also been described earlier. Psychopaths would learn from rewards rather than punishment. The early error detection signal is very weak and is not being used optimally. Not only the detection, but also the awareness of errors is affected. In addition, the psychophysiological reactions after negative feedback are not so much present as in healthy controls. Finally, risk taking tasks have shown that psychopaths frequently make decisions that are riskier.

What disorders are there in social cognition?

The disturbances in social cognition are noticeable in emotion, empathy and affect. A wide range of emotion-processing operations are disturbed. Various studies show that the autonomous responses to emotionally negative stimuli are the same as the response to neutral stimuli. There would even be a preference for the negative stimuli. In the social context too, learning based on negative feedback is not successful. Psychopaths also have reduced apathy abilities: they respond less to other people's ‘distress’, they are inaccurate in assessing vocal affective information, and they are worse at recognizing emotions based on facial expressions. In contrast to non-psychopathic criminals, psychopathic criminals have more difficulty in distinguishing between "moral transgression" (behavior that leads to harm to a person) and "conventional transgression" (behavior that disrupts social order such as speeding).

How does aggression relate to endocrine and genetic factors?

Psychopathy is often associated with aggression, and aggression is associated with serotonin, dopamine and noradrenaline. A lower level of serotonin induces uninhibited aggressive behavior. SSRIs and tryptophan can increase serotonin levels and reduce aggression. However, serotonin is part of a complex network and such simple drug treatment is therefore not necessarily effective (Kraemer, Schmidt & Ebert, 1997). There is a less strong relationship between dopamine and aggressive behavior. Sometimes antipsychotics are prescribed to block the dopamine receptors. Noradrenaline prepares the body for aggressive behavior (the fight part of the 'fight-or-flight' response). Here too, aggressive behaviour diminishes by administering drugs that block noradrenaline β receptors. In the area of ​​endocrine factors, there is a strong positive correlation between testosterone and violent and antisocial behavior. The increased level of testosterone can be a cause or a consequence of a dominant status. Psychopaths cannot transform social dominance into a socially acceptable manifestation. In combination with reinforcing factors (such as cognitive deficits and social incompetence), social destructive behavior develops.