What is the role of methods in cognitive neuroscience? - Chapter 3

Cognitive neuropsychology is the study of mental activities an information-processing problem. They seek to identify the internal processing that underlies observable behavior. A basic assumption is that people do not directly act on what they see and perceive in the world. Our ability to comprehend the information we are getting, depends on a complex interplay of processes. Cognitive psychologists design experiments to test hypotheses about mental operations by adjusting what goes into the brain and then seeing what comes out. 

In summary, two key concepts underlie the cognitive approach:

1. Information processing depends on mental representations

2. These mental representations undergo internal transformations

What are mental representations?

We usually take for granted the idea that information processing depends on mental representations. Context helps dictate which representational format is most useful. You can use experiments to see if we have multiple representations of stimuli. Such experiments always have an independent variable, this is the manipulated variable. The dependent variable is the event you are evaluating. But, as you may have experienced, experiments generally elicit as many questions as answers. 

What are internal transformations?

The second critical notion of cognitive psychology is that our mental representations undergo internal transformations. When you are taking action, you see and smell certain flavors and things and you brain transforms these sensations into perceptual representations, and, by processing them, enables you to decide on a course of action and to carry it out. So, cognitive psychology is all about how we manipulate representations. 

Sternberg (1975) introduced an experimental task that bears show some similarity to the problem faced by an absentminded shopper. The job is comparing sensory information with representations that are active in memory. In each trial, the participant sees a set of letters to memorize. Then he sees a single letter and must decide whether this letter was part of the memorized set. Sternberg postulated that, to response on this task, the participant must engage in four primary mental operations:

1. Encoding: the participant must identify the visible target

2. Comparing: the participant must compare the mental representation of the target with the representations of the items in memory

3. Deciding: the participant must decide whether the target matches one of the memorized items

4. Responding: the participant must respond appropriately for the decision made in Step 3

Sternberg's basic question was how to characterize the efficiency of recognition memory. A highly efficient system might simultaneously compare a representation of the target with all of the items in the memory set. Or, the recognition process might be able to handle only a limited amount of information at any point in time. Sternberg realized that the reaction time data could distinguish between these two alternatives. If the comparison process can be simultaneous for all items - a parallel process - then the reaction time should be independent of the number of items in the memory set. But if the comparison process operates in a sequential, or serial, manner, then reaction time should slow down as the memory set becomes larger. 

How do you study the damaged brain?

Cognitive psychologists assume that fundamental principles of cognition can be learned from this limited population but also recognize the importance of testing other populations. A core method in cognitive neuroscience involves testing a unique population - people who have suffered brain damage. 

What are causes of neurological dysfunction?

Vascular disorders

Neurons need a steady supply of oxygen and glucose. These substances are essential for the cells to produce energy, fire action potentials, and make transmitters for neuronal communication. A cerebral vascular accident, or stroke, occurs when there is a sudden disruption of the blood flow to the brain. The most frequent cause of stroke is occlusion of the normal passage of blood by a foreign substance. Other types of cerebral vascular disorder can lead to ischemia (inadequate blood supply). The vascular system is fairly consistent between individuals; thus, a stroke of a particular artery typically leads to destruction of tissue in a consistent anatomical location. 

Tumors

A tumor or neoplasm is a mass of tissue that grows abnormally and has no physiological function. Brain tumors are relatively common; most originate in glial cells and other supporting white matter tissues. 

Degenerative and infectious disorders

Many neurological disorders result from a progressive disease. Here we focus on the etiology and clinical diagnosis of degenerative disorders. They have been associated with both genetic aberrations and environmental agents. A prime example is the Huntington's disease, the link in other degenerative disorders, such as Parkinson's and Alzheimer's disease, is weaker. The diagnosis of degenerative disorders is usually confirmed by MRI scans. Viruses can also cause progressive neurological disorders. HIV and AIDS have the tendency to lodge in subcortical areas of the brain, producing diffuse lesions of the white matter by destroying axonal fibers resulting in dementia. 

Traumatic brain injury

The most common brain affliction that lands patients in a neurology ward is traumatic brain injury (TBI). Common causes of head injuries are car accidents, falls, contact sports, bullter or shrapnel wounds and bomb blasts. One consequence of the primary lesion from a TBI is edema (swelling) around the lesion. The limited space in the skull, due to the edema, causes an increase in the intracranial pressure, in turn reducing the perfusion pressure and flow of blood throughout the brain, resulting in inschemia and, in some cases, the emergence of secondary lesions. 

Epilepsy

Epilepsy is a condition characterized by excessive and abnormally patterned activity in the brain. The cardinal symptom is a seizure, a transient loss of consciousness. An EEG (electroencephalography) can confirm seizure activity. 

What a cognitive neuropsychologists wants to do is design tasks that will test specific hypotheses about brain-function relationships. Associating neural structures with specific processing operations calls for appropriate control conditions, the most basic control is to compare the performance of a patient or group of patients with that of healthy participants. 

What methods are there to perturb neural function?

The release of neurotransmitters at neuronal synapses and the resultant responses are critical for information transfer from one neuron to the next. Though protected by the blood-brain-barrier (BBB) the brain is not a locked compartment. Pharmalogical studies may involve the administration of agonist drugs, those that have a similar structure to a neurotransmitter and mimic its action, or antagonist drugs, those that bind to receptors and block or dampen neurotransmission. There are several studies regarding the influence of drugs on the brain. But one major drawback of studies using drugs injected into the bloodstream is the lack of specificity.

The start of the 21st century went hand-in-hand with the climax of one of the greatest scientific challenges: the mapping of the human genome. Genetic disorders are manifest in all aspects of life, including brain function. By analyzing individual's genetic codes, scientists can predict whether the children of individuals carrying the Huntington disease gene will develop his debilitating disorder. 

What are the invasive stimulation methods?

Given the risks associated with neurosurgery, researchers reserve invasive methods for studies in animals and for patients with neurological problems that require surgical intervention. An invasive approach is deep brain stimulation (DBS), a procedure in which surgeons implant electrodes in specific brain regions for an extended period to modulate neuronal activity. The most common application of this method is as a treatment for Parkinson's disease, a movement disorder resulting from the basal ganglia dysfunction. 

Optogenetics has provided a reliable switch to activate neurons using viral transduction. Scientists inserted the ChR-2 gene into the part of the mouse's brain that contains the motor neurons controlling its whiskers. Once the light-sensitive ion channels were constructed and a tiny optical fiber was inserted in the same region, the neurons were ready to rock'n'roll. 

What are noninvasive stimulation methods?

TMS or transcranial magnetic stimulation procused relatively focal stimulation of the human brain noninvasively. The area of neural activation depends on the shape and positioning of the TMS coil. There are numerous protocols, or ways in which stimulation can be manipulated. Researchers can administer TMS pulses at various intensities, timings, and frequencies. TMS has become valuable research tool in cognitive neuroscience because of its ability to induce 'virtual lesions'. But, TMS also has its limitations. With currently available coils, the area of primary activation has about a 1-cm radius and thus can activate only relatively superficial areas. 

Researchers are constantly looking for new ways to noninvasively stimulate the brain. Transcranial direct current stimulation (tDCS) is a brain stimulation procedure that delivers a constant, low current to the brain via electrodes placed on the scalp. A current is send between an anode and a cathode. The neurons under the anode become depolarized, they achieve an elevated state of excitability, making them more likely to initiate an action potential when a stimulus or movement occurs. The transcranial direct current stimulation procedures changes in a wide range of sensory, motor and cognitive tasks. 

Transcranial alternating current stimulation (tACS) is a newer procedure in which the electrical current oscillates rather than remaining constant as in tDCS. The experimenter controls the rate of tACS oscillation, providing another tool to modulate brain function. The direction and the duration of the tACS-induced effects can vary with the frequency, intensity and phase of the stimulation. 

Transcranial static magnetic stimulation (tSMS) uses strong magnets to create magnetic fields that, as with TMS, perturb electrical activity and thus temporarily alter cortical function. Another emerging method, one that promises improved spatial resolution and the ability to target deeper structures, is transcranial focused altrasound (tFUS). This signal increases the activity of voltage-gated sodium and calcium channels, thus triggering action potentials. 

What is the structural analysis of the brain?

We now turn to methods used to analyze brain structure. Structural methods take advantage of the differences in physical properties that different tissues possess. 

CT or CAT, computerized tomography scanning was the first method to offer an in vivo look at the human brain. This method was actually an extension of X-rays. Although CT scanning continuous to be an extremely important medical procedure for clinical purpose, magnetic resonance imaging (MRI) is now the preferred method for whole-brain imaging because it provides images of much higher resolution. MRI scans provide a much clearer image of the brain than is possible with CT scans. 

A variant of the traditional MRI is diffusion tensor imaging (DTI). This is used to study the anatomical structures of the axon tracts that form the brain's white matter, this method offers information about anatomical connectivity between regions. 

What methods are used to measure neural activity?

The development of methods for single-cell recording was perhaps the most important technological advance in the history of neuroscience. By measuring the action potentials produced by individual neurons in living animals, researchers could begin to uncover how the brain responds to sensory information, produces movement and changes with learning. The primary goal of a single-cell recording experiments is to determine which experimental manipulations produce a consistent change in the response rate of an isolated cell. 

A single cell is not responsive to all visual stimuli. A number of stimulus parameters might correlate with the variation in the cell's firing rate. An important factor is the location of the stimulus. All visually sensitive cells respond to stimuli in only a limited region of space. This region of space is that cell's receptive field. Neighboring cells have at least partially overlapping receptive fields. As such, cells form a topographic representation - in vision, we refer to topographic representations as retinotopic maps. 

What holds the invasive neurophysiology in humans?

Surgeons may insert intracranial electrodes to localize an abnormality before its surgical resection. A invasive neurophysiological method used to study the human brain is electrocorticography (ECoG), where a grid or strip of electrodes is placed directly on the surface of the brain, either outside the dura or beneath it, and the activity of the populations of neurons is recorded for a sustained amount of time. In a second procedure, they remove the electrodes and perform the corrective surgery. Researchers can stimulate the brain with the electrodes, using them to localize and map cortical and subcortical neurological functions such as motor or language function. The time-varying record of the signals from the electrodes is an electrocorticogram.

What are the noninvasive electrical recording of neural activity?

The electrical potential produced by a single neuron is minute; it would be impossible to detect that signal from an electrode placed on the scalp. When populations of neurons are active, they generate a much larger composite of electrical signal. You can measure those with noninvasively by using electrodes placed on the scalp, a method known as electroencephalongraphy (EEG). Because normal EEG patterns are consistent among individuals, we can detect abnormalities in brain function from EEG recordings. 

The data collected with an EEG can also be used to examine how a particular task modulates brain activity. The evoked response, or event-related potential (ERP) is a tiny signal embedded in the ongoing EEG triggered by the stimulus or movement. ERP's also provide an important tool for clinicians. The visual evoked potential can be useful in diagnosing multiple sclerosis, a disorder that leads to demyelination. 

Related to EEG is magnetoencephalography (MEG), a technique that measures the magnetic fields produced by the brain's electrical activity. As with EEG, the MEG traces over a series of trials to obtain event-related signals, called event-related fields. 

The marriage of function and structure: what is neuroimaging?

The most exciting advances for cognitive neuroscience have been provided by imaging techniques that enable researchers to identify the physiological changes in specific regions of the brain as people perceive, think, feel and act. The most prominent of these neuroimaging methods are positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). PET and fMRI do not directly measure neural events. Rather, they measure metabolic changes correlated with the neural activity. When a brain area is active, increasing the blood flow to that region provides it with more oxygen and glucose at the expense of other parts of the brain. PET and fMRI can detect this change in blood flow, known as hemodynamic response. 

Positron Emission Tomography

PET activation studies use radioactive-labeled compounds to measure local variations in cerebral blood flow that correlate with mental activity. The radiologist injects a tracer into the bloodstream, which distributes it throughout the brain in step with its metabolic needs. A common tracer isotope used in PET studies is the oxygen-15 (¹⁵O), which has a half life of 122 seconds. Although all areas of the body use some of the radioactive oxygen, the fundamental assumption of PET is that there is increased blood flow to the brain regions that have heightened neural activity. Thus, PET activation studies measure relative activity, not absolute metabolic activity. The results are usually reported as a change in regional cerebral blood flow (rCBF) between the control and experimental conditions. 

Functional magnetic resonance imaging

fMRI exploits the fact that local blood flow increases in active parts of the brain. Radio waves cause the protons in hydrogen aims to oscillate, and a detector measures the local energy fields emitted as the protons return to the orientation of the magnetic field created by the MRI scanner. The fMRI detectors measure the ratio of oxygenerated to deoxygenerated hemoglobin; this value is referred to as the blood oxygen level-dependent (BOLD) effect. 

fMRI offers several advantages over PET. MRI scanners are much less expensive and easier to maintain, and fMRI uses no radioactive tracers, so it does not incur the additional costs, hassles, and hazards associated with handling these materials. 

fMRI and PET differ in their temporal resolution. The PET imaging requires sufficient time for detecting enough radiation to create images of adequate quality. Because of this time requirement, the researchers must use block design experiments with PET. The researcher integrates the recorded neural activity over a 'block' of time during which the participant performs multiple trials of the same type. 

fMRI can either use a block design, in which the experimenter compares the neural activation between experimental and control scanning phases, or an event-related design. Event-related fMRI improves the experimental design because the researcher presents the experimental and control trials randomly. 

You can also use the MRI machine to measure other properties of brain tissue. One method, the magnetic resonance spectroscopy (MRS) offers a tool to obtain, in vivo, information about the chemical composition of tissues. From the MRS data, researchers can estimate the concentration of different neurochemicals in one brain area or the same neurotransmitter in multiple areas. 

What are limitations of functional imaging techniques?

1. PET and fMRI have poor temporal resolution compared with single-cell recordings or ERP's. PET is constrained by the decay rate of the radioactive agent, and fMRI is dependent on the hemodynamic changes that underlie the BOLD response. 

2. To relate function and structure, it is necessary to be able to map the data obtained with functional imaging methods such as fMRI and PET onto corresponding structural MRI scans. These methods work because brains, in general, have the same components, but, just like fingerprints, no two brains are the same. This variation presents a problem for comparisons of the functional imaging data across individuals. 

3. There is also a difficulty arising on the interpretation of the data from a PET of fMRI study. The data sets are massive, presenting challenging statistical problems. 

4. Even with proper statistical procedures, comparisons between different experimental conditions are likely to produce many differences. 

What is a connectivity map?

The last years there has been a lot of work regarding developing tools, to understand how the brain supports any cognitive process, this is called a connectivity map. These maps, often referred to as connectomes, are visualizations of structural or functional connections within the brain. A brain network can be constructed from either structural or functional imaging data:

1. Define the network nodes. Data from MRI and fMRI are divided into nodes, visualized in a parcellation map.

2. Measure the correlation between all possible pairs of nodes, using the dependent variable of interest.

3. Generate an association matrix by compiling all pairwise associations between the nodes. 

4. Visualize the correlations in connectivity map, one way to create these maps is to depict brain regions as nodes of a network and indicate connections as edges between them. 

So, the connectivity maps capture the correlated patterns of activity between different brain regions. They also give a new opportunity and new methods for examining variation between individuals or groups. 

What is computational neuroscience?

Creating computer models to simulate postulated brain processes is a research method that complements the other methods discussed in this chapter. A simulation is an imitation, a reproduction of behavior in an alternative medium. These simulated cognitive processes are commonly referred to as artificial intelligence (AI). Computer models are useful because we can analyze them in detail

Computer models differ widely in their representations. Symbolic models include units that represent symbolic entities. An alternative architecture that figures prominently in cognitive neuroscience is the neural network. Models can be 'lesioned' to test whether the resulting change in performance resembles the behavioral deficits observed in neurological patients. Lesioning thus provides a tool to assess whether the model accurately simulates a particular cognitive process or domain, and more important, to shed a light on the credibility of the model. 

What are converging methods?

Cognitive neuroscience is a interdisciplinary field that draws on ideas and methodologies from cognitive psychology, neurology, neuroscience, and computer science. The great strength of cognitive neuroscience lies in the ways that diverse methodologies are integrated.