Methods in Cognitive Neuroscience PDF
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Simon Fraser University
Banich & Compton
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This document provides an overview of different methods used in cognitive neuroscience to study brain function. It covers various techniques, including neuronal activity, synaptic regulation, and different brain systems.
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3 - Methods in Cognitive Neuroscience Review “If the human brain were so simple that we could understand it, we would be so simple that we couldn’t.” - Emerson M. Pugh We (me) don’t always have all the answers! Field of neuroscience is constantly evolving and changing based on new resear...
3 - Methods in Cognitive Neuroscience Review “If the human brain were so simple that we could understand it, we would be so simple that we couldn’t.” - Emerson M. Pugh We (me) don’t always have all the answers! Field of neuroscience is constantly evolving and changing based on new research Will spend review section on any lingering questions from previous lecture For example, the neuron to glia ratio… https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063692/ Astrocytes Main functions: Maintenance of water and ion homeostasis, Participation in the environment of the synapse Contribution to the blood-brain barrier How do Astrocytes regulate the environment of the synaptic cleft? “Astrocytes control the formation, maturation, and plasticity of synapses through a variety of secretory and contact-mediated signals” (Allen & Lyons, 2018). Regulate extracellular concentrations of ions, neurotransmitters, and other molecules through uptake and recycling. “When neurons fire action potentials, they release K+ ions into the extracellular space. Astrocytes express high concentrations of K+ channels, which act as spatial buffers. They uptake K+ at sites of neuronal activity (mainly synapses) and release it at distant contacts with blood vessels” (Kim et al., 2019). Directionality of Action Potentials Axon, not dendrites: For action potential to occur, there is the influx of sodium ions and efflux of potassium ions through the voltage-gated sodium and potassium channels respectively. Action potentials require voltage-gated ion channels. There aren't enough of these in the cell body or dendrites to propagate a signal. Unidirectional down the axon: A patch of membrane that has just undergone one action potential is in a “refractory period” and cannot undergo another to cause excitation in the other direction. Myelination Myelin Sheath +++++ +++++ +++++ Internode Length Myelination Precise control of timing is essential not only for motor skills and sensory processing but also for higher integrative functions, including cognition. Variations in myelin (including internode length) allow for control of the timing of neural inputs, slowing or speeding action potential propagation of some axons relative to other axons. Neurotransmitters Chemicals that neurons release that allow them to communicate They bind with receptors on the postsynaptic membrane This changes the configuration of the receptor and the electrical charge which alters the flow of ions across the membrane Excitatory postsynaptic potentials (EPSP) make the cell’s electrical charge more positive Inhibitory postsynaptic potentials (IPSP) make the cell’s electrical charge more negative Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Amino Acid Neurotransmitters Amino acids are found throughout the CNS Glutamate (15-20% of synapses) has an excitatory effect and too much can cause excitotoxicity GABA (gamma-aminobutyric acid) has an inhibitory effect. 40% of all receptors in the CNS are GABAergic Substances that reduce CNS activity bind to GABA receptors (ex. Barbiturates and alcohol). Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Other Neurotransmitters The second major class are organized into systems. Cell bodies are subcortical with axons projecting into the cortex. Cholinergic, serotonergic, noradrenergic, and dopaminergic systems. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Cholinergic System Neurotransmitter: Acetylcholine (ACh) Cell bodies of neurons located mainly in the basal forebrain nucleus and project to almost all portions of the cortex. ACh has a very general excitatory effect on neuronal and mental functioning. Plays a role in alertness and paying attention. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 FIGURE 1.18A Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Serotonergic System Neurotransmitter: Serotonin (5-HT) Cell bodies in the raphe nuclei of midbrain, pons, and medulla Project to the limbic system (hypothalamus, hippocampus, and amygdala), striatum, cortex, cerebellum, and thalamus. Influences variety of behaviors (ex. sleep, mood, sexual behavior, eating, and memory) Many antidepressant medications are serotonin-specific reuptake inhibitors (SSRIs) Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Figure 1.18B Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Noradrenergic System Neurotransmitter: Noradrenaline (or Norepinephrine) Originates primarily in the locus coeruleus. Project to thalamus, hypothalamus, and cortex (large influence on prefrontal cortex) Influences arousal and attention, also linked to both shorter-term and longer-term aspects of memory processing. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 FIGURE 1.18C Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Dopaminergic System Neurotransmitter: Dopamine Nigrostriatal – cell bodies in the substantia nigra, project to neostriatum (part of basal ganglia); important in motor control. Mesolimbic – cell bodies in the ventral tegmental area (VTA), project to limbic system; linked to reward-related control. Mesocortical - also in the VTA, project to much of the cortex (especially motor cortex, premotor cortex, and prefrontal cortex); influence a variety of mental functions, including executive function (goal-oriented behaviour – planning and problem-solving) as well as working memory. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 FIGURE 1.19 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Methods in Cognitive Neuroscience Introduction Information can be obtained about the brain at various levels: Neuroanatomical, Neurochemical, Neurophysiological Cognitive neuroscientists must consider how the information they gather is influenced by the choice of a particular population and a particular method. Researchers aim to gather information using the method of converging operations. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Clinical Populations vs Neurologically Intact Clinical Populations: Researchers may examine whether degree of brain activation (or deactivation) shows a significant relationship with a particular characteristic of a clinically relevant group of people Is increased severity of dependence on alcohol associated with decreased volume in a particular brain structure? Is increasing levels of inattention in children with ADHD associated with reduced activation in specific brain regions during cognitive tasks? Clinical Populations vs Neurologically Intact Neurologically Intact: Serve as a critical reference population in lesion studies Allow researchers to determine the degree to which the performance of individuals with brain damage is compromised. Lesion group and the neurologically intact control group must be matched as thoroughly as possible on demographic characteristics The basics of MRI Powerful cognitive neuroscience tool that can provide information about brain anatomy AND functioning. MRI machines create a constant magnetic field. Perturbations in this field are induced The response of the atoms in the brain is used to derive maps of brain structure and function. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Magnetic Resonance Imaging (MRI) Figure 3.2 Provides information about the size and An example of group differences in subcortical shape. shape of different brain structures. For cortical structures, researchers often examine volume, determining if it differs between groups (ex. Clinical populations). For subcortical structures, researchers examine volume AND variations in shape. Orr et al., 2016 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Diffusion Tensor Imaging (DTI) Provides information about: Anatomical connectivity between different brain regions White matter integrity Detects the main axis along which water diffuses in nerve fibers and this indicates the main directional orientation of white-matter tracts The degree of diffusion provides information on the structural integrity of those tracts Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Diffusion Tensor Imaging (DTI) from Mori and Zhang, 2006 Figure 3.3 Diffusion Tensor Imaging Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 DTI Tractography DTI can be used to: Identify effects of demyelinating disorders Detect areas with partial or complete disconnection between brain regions Examine changes in diffusion during different life stages Diffusion tractography uses such diffusion tensor information to build an image of probable white-matter tracts. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 An Example of DTI Tractography from Forkel et al., 2014 Figure 3.4 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Positron Emission Tomography (PET) Works by introducing radioactive atoms into the blood supply to be carried to the brain. Superseded by functional MRI Can provide invaluable information regarding: Neurotransmitter function (especially dopamine) Absolute levels of brain metabolism: Absolute measure of regional cerebral blood flow (rCBF) Cerebral metabolic rate of oxygen consumption Cerebral glucose metabolism Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Example of PET Image Figure 3.5 Example of a PET image from a study designed to detect dopaminergic activity. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 PET Advantages and Disadvantages Advantages: Allows researchers to examine how the brain uses specific molecules (ie. neurotransmitters) Provides information on absolute levels of brain metabolism Disadvantages: Involves radiation, can only do 2-5 times per year safely Poor temporal resolution (time period to get image of brain activity longer than time in which mental operations performed) Need to continually create radioactive isotope with expensive cyclotron Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Functional Magnetic Resonance Imaging (fMRI) BOLD (blood oxygen level dependent) signal Based on the fact that oxygenated and deoxygenated blood have different magnetic properties. When an area of the brain is active, the local increase in oxygen-rich blood is greater than the amount of oxygen that can be extracted by the brain tissue. Thus, the relative proportion of oxygenated blood to deoxygenated blood increases in that local region. Deoxygenated blood hinders ability to get a signal, increased proportion of oxygenated blood to deoxygenated Figure 3.7 blood results in increased signal from that region. Time course of the fMRI signal This increased signal is a hemodynamic effects that takes from the onset of a stimulus. about 8-10 seconds to observe. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Advantages of fMRI Machines widely available Non-invasive Multiple scans possible Safe for children and women of reproductive age Measure brain activity over seconds (better than PET) Scans can provide information about specific individuals (ex. useful prior to Figure 3.8 A typical set-up for MRI. neurosurgery) Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Task-Based Approaches Majority of fMRI studies examine brain activity during the performance of a task Requires non-metallic devices to convey information to the participant and to record responses Studies can examine the change in signal from one condition to another (baseline) condition The selection of the baseline task is critical for interpretation of the results. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Maps using fMRI Maps show which voxels are significantly more activated Can determine whether these patterns of activation vary across groups Can determine whether the activation is related to a from Andrews-Hanna et al., 2011 demographic or personality trait. Figure 3.9 Maps of brain activation from an fMRI experiment. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Resting-state Approaches Examine patterns of activity while the brain is at rest Researchers have found “independent” networks (regions that co-activate during specific tasks) Advantages Doesn’t require specific cognitive ability or engagement from participant Relatively short neuroimaging session (10–15 minutes) Yeo et al., 2011 Figure 3.11 Seven major brain networks derived from brain activation at rest Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Brain Connectivity Can be examined: during performance of a task, during rest, and across groups to determine if there are differences When significant relationships are observed, scientists often refer to this phenomenon as functional connectivity. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Electromagnetic Recording Methods Provide the best temporal resolution of brain activity. Activity can be measured on a millisecond-by-millisecond basis Do not provide a good measure of where in the brain activity is occurring Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Electroencephalography (EEG) Measures electrical activity in the brain using electrodes Electroencephalography (EEG) Measures electrical activity of cortical neurons near the electrodes on the scalp Advantages: Disadvantages: High temporal Low spatial resolution resolution Cannot reach structures Non-invasive deep within the brain Relatively cheap Relatively long prep time Equipment is mobile and accessible Event-related Potentials (ERP) EEG: continuous measure of brain activity ERP: recorded in reference to a specific event Characterized by distinct components. Figure 3.14 Examples of the late positive potential. Schupp et al., 2000 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Magnetoencephalography (MEG) Records magnetic potentials produced by brain activity. Used clinically to: Localize the source of epileptic activity Locate primary sensory cortices during neurosurgical intervention. Also used to understand a variety of cognitive processes Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Magnetoencephalography (MEG) Advantages: Magnetic fields not as influenced by different tissue types (as electrical currents are in EEG) Strength of magnetic field is systematic, so some information about depth of source in the brain. Disadvantages: Requires a large and complicated device in a room magnetically shielded against the earth’s magnetic field and other sources of electromagnetic radiation. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Optical Recording Methods Provides information about the source AND time course of neural activity A laser source of near-infrared light is positioned on the scalp. Optic fiber detectors are located a few centimetres away These detectors sense how the path of light is altered by: Absorption (slow signal) in oxygenated and deoxygenated blood Scattering (fast signal) related to physiological characteristics such as the swelling of glia and neurons that are associated with neuronal firing. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Principles of Optical Imaging Figure 3.17 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Optical Recording Methods Ex. Functional near-infrared spectroscopy (fNIRS) Advantages: Absorption of light different for oxygenated and deoxygenated blood, can tell them apart (whereas BOLD is ratio only) Can provide information about oxygenation of the brain System relatively small and portable Disadvantages: Cannot obtain information about subcortical regions (too much light absorbed) Does not provide precise localization of activation. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Transcranial Magnetic Stimulation (TMS) Figure 3.18 Can allow observation of cause and effect. Transcranial magnetic stimulation can be A pulsed magnetic field over the scalp induces an used to alter ongoing electrical field which alters the membrane potential brain activity. of neurons When the pulsed magnetic field is discontinued, the neurons return to their previous state. Can be used either to increase or decrease neuronal activity depending on pulse given The method is most effective for cortical structures From www.mayoclinic.org/tests- procedures/transcranial-magnetic- stimulation/home/ovc-20163795 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Transcranial direct current stimulation (tDCS) A weak electrical current runs between an entrance and exit electrode in order to: Create a “virtual lesion” (via cathodal stimulation) Enhance activity (via anodal stimulation). Stimulation is less intense (safer), but also less focused spatially Currently clinical investigations: Reducing cravings in addiction Reducing auditory hallucinations in individuals with schizophrenia Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Example tDCS Set-up from http://jamanetwork.com/data/Journals/NEUR/22588/nnr80008f1.jpg Figure 3.19 Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Multilevel and Multimodal Approaches Involve using multiple tools in tandem. Researchers combine information from several measures derived from the same acquisition technique E.g., sMRI provides brain anatomy and fMRI provides brain function information Researchers can combine information from two, complimentary measures that have differing strengths E.g., Functional MRI to provide information on where and ERPs to provide information on when activity is occurring Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Meta-Analyses Meta-analyses determine whether similar results are obtained across multiple different studies When a pattern is observed, there is more confidence in the conclusions drawn about brain–behavior relationships Can make use of method of converging operations. Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Methods of assessing Advantages Disadvantages brain anatomy CAT (computerized axial Can be used with almost all a. Involves the use of ionizing tomography) individuals radiation b. Does not provide high spatial resolution Anatomical MRI a. Cannot be used with individuals a. Can be used to detect (magnetic resonance who have metal in their bodies or imaging) different substances pacemakers b. Allows white matter tracts to b. Can induce claustrophobia in some be visualized via diffusion individuals weighted imaging c. Does not involve radiation; good spatial resolution Banich & Compton, Cognitive Neuroscience © Cambridge University Press & Assessment 2023 Methods of assessing brain physiology Functional brain imaging PET (positron emission Can be used to assess many a. Involves the use of ionizing tomography) aspects of physiological radiation (which limits an individual to function 4–5 scans per year) b. Provides images averaged over times longer than required for typical mental operations (e.g., word recognition) MRS (magnetic resonance a. Limited to only a certain subset of a. Provides information about spectroscopy) compounds that are found in large neurochemical processes concentrations in the brain b. Does not involve the b. Information must be gathered from ionizing radiation associated a large region of brain tissue, so that with PET precise localization is not possible fMRI a. Provides good spatial a. Cannot be used with individuals resolution in relatively short who have metal in their bodies or time periods (half a second) pacemakers b. Limited ways of measuring physiological function: (1) provides b. Can be performed information only on relative repeatedly on the same oxygenation of the blood; (2) individual measures the brain’s hemodynamic response that occurs on the order of seconds c. Widely available d. Can be analyzed in a variety of ways to examine brain networks and brain connectivity Electromagnetic recordings Provides information on the Not feasible in humans except under Single-cell type of stimulus to which a cell very specific circumstances responds EEG (electro a. Provides information on the a. Difficult to determine the source of encephalography) general state of the person activity from within the brain (e.g., alert, drowsy) b. Provides excellent temporal b. Difficult to detect activity of cells resolution oriented parallel to the brain’s surface ERP (event-related a. Provides information that potentials) has been linked to specific a. Difficult to determine the source of psychological processes such activity from within the brain as memory and attention b. Provides excellent temporal b. Difficult to detect activity of cells resolution oriented parallel to the brain’s surface MEG (magneto a. Provides better information a. Set-up is large and elaborate, encephalography) than EEG/ ERP about the requiring a shielded room source of the signal b. Not as susceptible to b. Cannot detect cells with differences in conduction of orientations radial to the brain’s tissue intervening between the surface brain and scalp Optical recordings Functional near-infrared a. Cannot provide information on a. Noninvasive optical spectroscopy subcortical structures (fNIRS) b. Can measure only the b. Inexpensive hemodynamic response of the brain c. Portable d. Allows the concentration of oxygenated and deoxygenated blood to be calculated separately Methods of Modulating Brain Activity TMS (transcranial a. Very very small but possible a. Can be used to confirm magnetic stimulation) potential adverse effects on brain findings from lesion method functions (e.g., seizures) b. Can be used therapeutically b. Can only stimulate regions close to to treat clinical syndromes the surface c. Does not allow for precise c. Can provide information on localization of effects but better than brain reorganization tDCS d. Can provide information about the functional connectivity of brain regions by determining effects at sites other than those stimulated. e. Can be used to determine whether a deficit results from dysfunction of a region or disconnection of brain regions tDCS (transcranial direct a. Provides information similar current stimulation) to TMS b. Is relatively easy and a. Only provides diffuse stimulation to portable to use the brain and hence cannot be well directed to specific brain regions c. Is less powerful than TMS and hence is generally well tolerated tACS (transcranial a. Similarly to tDCS, it is alternating current relatively easy and portable to stimulation) use a. Like tDCS, the localization of effects are not highly specific b. Allows for the modulation of brain oscillations Wednesday: Motor Control