Chapter 3 - Methods.docx

Though this be madness, yet there is method in't. *William Shakespeare* Methods of Cognitive Neuroscience ================================= - Why is cognitive neuroscience an interdisciplinary field? - How do the various methods used in cognitive neuroscience research differ in terms of t...

Though this be madness, yet there is method in't. *William Shakespeare* Methods of Cognitive Neuroscience ================================= - Why is cognitive neuroscience an interdisciplinary field? - How do the various methods used in cognitive neuroscience research differ in terms of their spatial and temporal resolution? - How do these differences impact the kinds of insights that can be drawn? - Which methods rely on drawing inferences from patterns of correlation, and which methods allow **73** ### Cognitive Psychology and Behavioral Methods 1. Information processing depends on mental represen- tations. 2. These mental representations undergo internal trans- formations. Mental Representations 1,000 900 800 700 600 500 letter vowels consonants categories Internal Transformations 1. *Encoding.* The participant must identify the visible target. 2. *Comparing.* The participant must compare the men- tal representation of the target with the representa- tions 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 appropri- ately for the decision made in Step 3. Constraints on Information Processing TAKE-HOME MESSAGES - Cognitive psychology focuses on understanding how the brain represents and manipulates objects or ideas. - Fundamental goals of cognitive psychology include identify- ing the mental operations that are required to perform cogni- tive tasks and exploring the limitations in task performance. 2. ### Studying the Damaged Brain Causes of Neurological Dysfunction a. Strokes occur when blood flow to the brain is disrupted. This brain is from a person who had an occlusion of the middle cerebral artery. The person survived the stroke. After death, a postmortem analysis showed that almost all of the tissue supplied by this artery had died and been absorbed. b. This coronal brain section is from a person who died following a cerebral hemorrhage. The hem- orrhage destroyed the dorsomedial region of the left hemisphere. The effects of a cerebral vascular accident 2 years before death can be seen in the temporal region of the right hemisphere. -- -- -- -- -- -- -- -- -- -- -- -- a. Ventral view of the brain of a 54-year-old man who sustained a severe head injury 24 years before death. Tissue damage is evident in the orbitofrontal regions and was associated with intellectual deteri- oration after the injury. **(b)** The susceptibility of the orbitofrontal region to trauma was made clear by A. Holbourn of Oxford, who in 1943 filled a skull with gelatin and then violently rotated the skull. Although most of the brain retains its smooth appearance, the orbitofrontal region has been chewed up. b. Activity during a grand mal seizure. Studying Brain--Behavior Relation- ships Following Neural Disruption TAKE-HOME MESSAGES - Researchers study patients with neurological disorders or brain lesions to examine structure--function relation- ships. Double dissociations are better evidence than single dissociations that damage to a particular brain region may result in a selective deficit of a certain cogni- tive operation. - Traumatic brain injuries are the most common cause of brain lesions. Even when the injuries are mild, they can have chronic neurodegenerative consequences. - Impairments in a particular cognitive process do not mean that the damaged part of the brain "performs" that pro- cess. Brain lesions can disrupt processing in intact brain structures or disrupt brain networks on a larger scale. 3. ### Methods to Perturb Neural Function Pharmacology Fixation Genetic Manipulations 10 Invasive Stimulation Methods Noninvasive Stimulation Methods **c** TAKE-HOME MESSAGES - Brain function can be perturbed by drugs, genetic ma- nipulations, and magnetic or electrical stimulation. In most cases, these methods allow the same participants to be tested in both "on" and "off" states, enabling within-participant comparisons of performance. - Genetic manipulations have played a major role in neuro- science studies using animal models. Knockout technol- ogy enables scientists to explore the consequences of the lack of expression of a specific gene in order to de- termine its role in behavior. Optogenetic methods provide the experimenter with the ability to control neuronal activity in targeted cells. - Noninvasive stimulation methods perturb neural activ- ity in healthy and neurologically impaired humans. By varying the stimulation protocols, we can enhance or suppress neural activity in targeted regions. 4. ### Structural Analysis of the Brain Visualizing the Gross Anatomy of the Brain  c. Comparing this CT image to the transverse slice on the left in part (b) reveals the finer resolution offered by MRI. Both images show approximately the same level of the brain. d. Resolution and clarity differences between 3.0-T and 7.0-T MRI images. \ TAKE-HOME MESSAGES - Computerized tomography (CT or CAT) and magnetic res- onance imaging (MRI) provide 3-D images of the brain. - The spatial resolution of MRI is superior to CT. - Diffusion tensor imaging (DTI), performed with an MRI scanner, measures white matter pathways in the brain and provides information about anatomical connectivity between regions. Visualizing the Structural Connectivity of the Brain a. This axial slice of a human brain reveals the directionality and connectivity of the white matter. The colors correspond to the principal directions of the white matter tracts in each region. b. DTI data can be analyzed to trace white matter connections in the brain. The tracts shown here form the inferior fronto-occipital fasciculus, which, as the name suggests, connects the visual cortex to the frontal lobe. 5. ### Methods to Measure Neural Activity Single-Cell Neurophysiology in Animals **a** a. An electrode is attached to a neuron in the optical cortex. Visual cortex b. Metabolically active cells in the visual cortex absorb the agent, revealing how the topography of Invasive Neurophysiology in Humans 250 128 64 32 1 0  Noninvasive Electrical Recording of Neural Activity 2 μV N1, P2 Midlatency components Cochlea - Magnetoencephalography (MEG) measures the magnetic signals generated by the brain. Sensitive magnetic detec- tors placed along the scalp measure the small magnetic fields produced by the electrical activity of neurons. We can use MEG in an event-related manner similar to ERPs, with similar temporal resolution. The spatial resolution can be superior because there is minimal distortion of mag- netic signals by organic tissue such as the brain or skull. 6. ### The Marriage of Function and Structure: Neuroimaging TAKE-HOME MESSAGES - Single-cell recording enables neurophysiologists to re- cord from individual neurons and correlate increases and decreases in neuronal activity with sensory stimulation or behavior. With multiunit recording, we can record the activity of many neurons at the same time. - Electrocorticography (ECoG) and electroencephalography (EEG) are two techniques to measure the electrical activ- ity of the brain. In ECoG, the electrodes sit directly on the brain; in EEG, the electrodes are on the scalp. These methods can measure endogenous changes in electrical activity, as well as changes triggered by specific events (e.g., stimuli or movements). Although the resolution of ECoG signals is much greater than that of EEG, it is used only in people undergoing neurosurgery. - An event-related potential (ERP) is a change in electrical activity that is time-locked to specific events, such as the presentation of a stimulus or the onset of a response. To Positron Emission Tomography −5 0 5 10 15 20 Time after stimulus onset (s) Functional Magnetic Resonance Imaging 3. Mov. Stat. Mov. Stat. 2 1 0 −1 4. Mov. Stat. Mov. Stat. Time (s) a. Primary visual cortex b. Area MT Event-related 0 a. Posterior LIFG  b. Parahippocampal/fusiform gyri 4 3 2 1 0 c. Left visual cortex **d** Right motor cortex 0.8 0.7 0.6 0.5 0.4 1.5 1.7 1.9 1.2 GABA (arbitrary units) 0.8 0.7 0.6 0.5 0.4 Limitations of Functional **c** 7.0 6.0 Glutamate (arbitrary units) Imaging Techniques \ TAKE-HOME MESSAGES - Positron emission tomography (PET) measures metabolic activity in the brain by monitoring the distribution of a decaying radioactive tracer. A popular tracer for cognitive studies is ^15^O because the distribution of oxygen increases in neural regions that are active. Researchers can design tracers to target particular types of tissue. The PiB tracer was designed to bind to beta-amyloid, providing an in vivo assay of an important biomarker for Alzheimer's disease. - In functional magnetic resonance imaging (fMRI), the MRI scanner is configured to measure changes in the oxygen content of the blood (hemodynamic response). We assume these changes correlate with local changes in neural activity. - In magnetic resonance spectroscopy (MRS), the MRI scan- ner is configured to target specific metabolites, providing a tool to measure the concentration of neurotransmitters. - Compared to methods that measure electrical signals, PET and fMRI have poor temporal resolution, averaging metabolic signals over seconds or even minutes. How- ever, we can use them simultaneously to obtain images of the entire brain with reasonable spatial resolution. ### Connectivity Maps 1 2 : : *N* Time (*t*) 1. Define the network nodes. Data from structural im- aging methods such as anatomical MRI or fMRI are divided into nodes, visualized in a parcellation map. With EEG and MEG, the sensors can serve as the nodes. 2. Measure the correlation between all possible pairs of nodes, using the dependent variable of interest---for example, fractional anisotropy (a measure of diffu- sion) for DTI, or BOLD response for fMRI. 3. Generate an association matrix by compiling all pairwise associations between the nodes. 4. Visualize the correlations in a 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. The geometric relationships of the nodes and edges define the network and provide a visualization of brain organization.   a. Differential power (DP)  b. Group consistency () \ TAKE-HOME MESSAGES - Connectivity maps capture correlated patterns of activity between different brain regions. Researchers derive these maps from fMRI data obtained during both a resting-state scan (while engaged in no task) and an active-state scan (while performing a task). - Data from rs-fMRI have revealed a relatively small set of intrinsic networks across the cerebral cortex. These - Connectivity maps offer new methods for examining variation between individuals or groups. For example, one can ask about the neural correlates associated with individual differences in intelligence or skill learning, or ask how individuals with a psychiatric condition differ from healthy individuals. ### Computational Neuroscience Representations in Computer Models Models Lead to Testable Predictions \ TAKE-HOME MESSAGES - We can use computer models to simulate neural networks in order to ask questions about cognitive processes - Models can be "lesioned" to test whether the result- ing change in performance resembles the behavioral ### Converging Methods 10 ms 0.0 Allele \ TAKE-HOME MESSAGES - We can gain powerful insights into the structural and functional underpinnings of cognitive behavior from experiments that combine methods. - Combining methods may enable progress from corre- lational observations to experimental approaches that provide inferential tests of causation. R IPL **dIPFC TMS** **S1 TMS** #### Summary Brain Map PET DTI --2 Millisecond #### Key Terms  #### Think About It 1. To a large extent, progress in all scientific fields depends on the development of new technologies and methodologies. What technological and methodologi- cal developments have advanced the field of cognitive neuroscience? 2. Cognitive neuroscience is an interdisciplinary field that incorporates aspects of neuroanatomy, neurophysiol- ogy, neurology, and cognitive psychology. What do you consider the core feature of each discipline that allows it to contribute to cognitive neuroscience? What are the limits of each discipline in addressing questions related to the brain and mind? 3. In recent years, functional magnetic resonance imaging (fMRI) has taken the field of cognitive neuroscience by storm. The first studies with this method were reported in the early 1990s; now hundreds of papers are pub- lished each month. Provide at least three reasons why this method is so popular. Discuss some of the tech- nical and inferential limitations associated with this method (*inferential*, meaning limitations in the kinds 4. Research studies show that people who performed poorly on spatial reasoning tasks have reduced volume in the parietal lobe. Discuss why caution is advised in assuming that poor reasoning is caused by the smaller size of the parietal lobe. To provide a stronger test of causality, outline an experiment that involves a train- ing program, describing your conditions, experimental manipulation, outcome measures, and predictions. 5. Consider how you might study a problem such as color perception by using the multidisciplinary techniques #### Suggested Reading **123**