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Chapter 4

PSYC55 - Cognitive Neuroscience Ch. 4 (pg. 120-)

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Pare, Dwayne

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PSYC55 – Chapter 4 (pg. 120 - ) Experimental Techniques Used With Animals  Damage in one part of the brain may disturb function in another part  The brain is a plastic device: neural function is constantly being reshaped by our experiences  Use of animals in scientific research allows researchers to adopt a more experimental approach Single-Cell Recording  Most important technological advance in neurophysiology was the development of methods to record the activity of single neurons in lab animals  Single-cell recording enabled researchers to describe response characteristics of individual elements  A thin electrode is inserted into the animal’s brain; if the electrode is in the vicinity of a neuronal membrane, electrical changes can be measured  Single-cell recording is typically done extracellularly (electrode is situated outside the neuron) o Problem: there is no guarantee that the changes in electrical potential at the electrode tip reflect the activity of a single neuron  Baseline activity varies widely from one brain area to another  Primary goal of single-cell recording experiments is to determine experimental manipulations that produce a consistent change in the response rate of an isolated cell  Neurophysiologist is interested in what causes change in the synaptic activity of a neuron  For sensory neurons, experimenter might manipulate the type of stimulus presented to the animal. For motor neurons, recordings can be made as the animal performs a task  Recordings are obtained from a series of cells in targeted area of interest  Functional maps can describe similarities and differences between neurons in a specified cortical region  One area where the single-cell method has been used extensively is the study of the visual systems of primates o Researcher targets the electrode to a cortical area that contains cells thought to respond to visual stimulation o Once a cell is identified, the researcher tries to characterize its response properties o A single cell is not responsive to ALL visual stimuli o All visually sensitive cells respond to stimuli in only a limited region of space called the receptive field o Sizes of receptive fields of visual cells vary  They are smallest in primary visual cortex and largest in association visual areas o A stimulus will cause a cell in primary visual cortex to increase its firing rate only when it is positioned in a very restricted region o Displacing a stimulus over a large distance may produce a similar increase in the firing rate of visually sensitive cells in the temporal lobe o External space is represented in a continuous manner across the cortical surface: neighboring cells have receptive fields of neighboring regions of external space o Cells form topographic representation (referred to as retinotopic representations) o Retina is composed of continuous sheet of photoreceptors o Visual cells in the subcortical and cortical areas maintain retinotopic info o Visual areas provide a representation of the location of the stimulus and cell activity within a retinotopic map correlates with the location of the stimulus  Auditory areas in the subcortex and cortex contain tonotopic maps, in which the physical dimension reflected in neural organization is the sound frequency of a stimulus  Neighboring cells tend to be tuned to similar frequencies  Sound frequencies are reflected in cells that are activated upon the presentation of a sound  Tonotopic maps are sometimes referred to as cochleotopic because the cochlea contains hair cells tuned to distinct regions of the auditory spectrum  The function of an area might be better understood by identification of the correlations in the firing patterns of groups of neurons rather than by identification of the response properties of each individual neuron o Inspired development of new techniques that allow recordings to be made in many neurons simultaneously (multiunit recording)  Multiunit recordings from motor areas of the brain are now being use to allow animals to control artificial limbs  Multiunit recordings can be obtained while people think about actions they would like to perform and this info can be analyzed by computers to control artificial limbs Lesions  If a neural structure contributes to a task, then rendering the structure dysfunctional should impair the performance of that task  Human neuropsychology involves research with patients who have suffered naturally occurring lesions  Lesioning a neural structure will eliminate that structure’s contribution but it might also force the animal to change its normal behavior and alter the function of intact structures  Lesion might also cause the animal to develop a compensatory strategy to minimize the consequences of the lesion  Most lesions were originally made by the aspirations of neural tissue o A suction device is used to remove the targeted structures  Another method was to apply electrical charges strong enough to destroy the tissue o Problem: it is difficult to be selective; tissues within the range of the voltage generated by the electrode tip will be destroyed  Most notable are neurochemical lesions o Sometimes a drug will selectively destroy cells that use a certain transmitter o Kainic acid is used in many studies because its toxic effects are limited to cell bodies  Some researchers choose to make reversible lesions using chemicals that produce a transient disruption in nerve conductivity o Appeal of this method is that each animal can serve as its own control o When the drug wears off, function gradually returns  In different form of reversible lesion, neural tissue is cooled by the injection of a chemical that induces a low temperature o When the tissue is cooled, metabolic activity is disrupted, creating a temporary lesion  Pharmacological manipulations also can be used to produce transient functional lesions Genetic Manipulations  One of the greatest challenges of the 21 century was the mapping of the human genome  Certain diseases, such as Huntington’s , are clearly heritable o In this particular disease, the differences were restricted to a single chromosomal abnormality o This discovery is expected to lead to new treatments  Scientists have sought to understand other aspects of normal and abnormal brain function through the study of genetics o Rats that are quick to learn to navigate mazes are likely to have offspring with similar abilities even if the offspring is raised by rats that are slow to navigate  Fruit fly and mice are 2 species with reproductive propensities that allow them to be studied for generations over short time period  A key methodology to develop genetically altered animals is knockout procedures o Knockout comes from the fact that specific genes have been manipulated so that they are no longer present or expressed o Scientists can study the new species to explore the consequences o Knockout procedures have been used to create strains that lack single types of postsynaptic receptors in specific brain regions while leaving intact other types of receptors o Knockout strains lacking the NMDA receptor in the hippocampus exhibit poor learning in a variety of memory tasks o This approach constitutes a lesion method at a microscopic level The New Genomics  It is widely recognized that complex brain functions and behavior arise from interactions between many genes and the environment  Gene expression can be used to study genes that underlie specific behaviors o Ex. Study found that orchestrated, differential hippocampal gene expression is necessary for long-term memory consolidation Neurology  Discoveries concerning the contralateral wiring of sensory and motor systems were made by physicians attending to warriors with open head surgeries  Postmortem studies were instrumental in linking left hemisphere to language functions th  First decades of the 20 century were the beginning of neuropsychology as a specialty within medicine Structural Imaging of Neurological Damage  Brain damage can result from o Vascular problems o Tumors o Degenerative disorders o Trauma  Computed tomography (CT or CAT scan) is an advanced version of the X-ray o X-ray compresses 3D into 2D; whereas CT allows for reconstruction of 3D space from compressed 2D images  To undergo a CT, patient lies supine in a scanning machine that has 2 parts located on opposite sides of the scanner; the sides rotate to project beams in all directions o X-ray source o Radiation detectors  Key principle underlying CT is that the density of biological material varies and the absorption of X-ray radiation is correlated with tissue density  Reconstructed images are contrast-reversed o High density areas show up as light colored and vice versa o Most of the cortex and white matter appear homogenous gray  It is very difficult to discriminates between white and gray matter on the CT scan o They are of similar density and very close to each other  Large structures however are identified easily o Eye sockets and skull appear white because of the high density of bone o Ventricles show up as black because of the low density of CSF  Magnetic Resonance Imaging (MRI) o Exploits the magnetic properties of organic tissue o Creates a powerful magnetic field o When a person is placed within the magnetic field in the MRI machine, significant proportion of protons become oriented in the direction parallel to the magnetic force o Radio waves are passed through the magnetized regions, and as the protons absorb the energy in these waves, their orientation is perturbed o When the radio waves are turned off, the absorbed energy is dissipated and the protons rebound toward the orientation of the magnetic field  This synchronized rebound produces energy signals that are picked up by detectors surrounding the head o The MRI can construct an image reflecting the distribution of the protons and other magnetic agents in the tissue o Provide a clearer image than CT scan o Density of protons is much greater in gray matter than in white matter o It is easy to see the sulci and gyri of the cortex  Diffusion Tensor Imaging (DTI) o Uses MRI scanners to study the microscopic anatomical structure of the axon tracts that form the white matter o Measures the density and water contained in the axons o Uses the diffusion characteristics of water to determine the boundaries that restrict water movement throughout the brain o Free diffusion of water = isotropic (occurs equally in all directions) o Diffusion of water in the brain is anisotropic (restricted because of the axon membrane) o Anisotropy is greatest in axons because myelin creates a lipid boundary limiting the flow of water to a much greater extent than gray matter or CSF does o MRI principals and water diffusion can be used to determine the diffusion anisotropy for each region (voxels) within the MRI scan o By using 2 large pulses to the magnetic field, we can make MRI signals sensitive to the diffusion of water  First pulse – determines the initial position of protons carried by water  Second pulse – detects how far protons have moved in space in the specific direction that is being measured o It is standard to acquire DTI images in more than 30 directions Causes of Neurological Disorders  Vascular disorders o The brain uses 20% of all the O2 we breathe o Loss of O2 for as long as 10 minutes can result in neural death o Angiography is a method used to visualize the distribution of blood in the brain by highlighting the major arteries and veins o O2 and glucose are distributed to the brain through 4 primary arteries  2 internal carotid arteries  Each one branches on to anterior cerebral and middle cerebral artery  Supply the anterior and middle portions of the cortex  2 vertebral arteries  Both join to form the basilar artery which irrigates the cerebellum and posterior part of brainstem  Branches into 2 posterior cerebral arteries providing blood to occipital and medial temporal lobe o The major cerebral arteries overlap in regions known as watersheds OR border zones o CVAs (cerebral vascular accidents) or strokes occur when blood flow to the brain is suddenly disrupted most commonly due to occlusion in the normal passage of blood by a foreign substance o An embolus (formed by arteriosclerosis) can enter the cranium and get stuck in the large carotid and vertebral arteries, blocking blood flow ( if not restored rapidly, cells die) o Onset of stroke is varied  Person may lose consciousness and die within minutes (infarct is in vicinity of brainstem)  May be sudden loss of speech and comprehension (infarct is cortical)  Person may report minor headache (innocuous onset) o Ischemia can be caused by a partial block in blood flow by an embolus or a sudden drop in BP that prevents blood from reaching the brain o Sudden rise in BP can lead to cerebral hemorrhage o Cerebral arteriosclerosis is when cerebral blood vessels become narrow due to thickening and hardening of the arteries  Can result in persistent ischemia  Condition is worse when person has an aneurysm which may expand or burst  CT can reveal this problem; surgery is required  Tumors (neoplasm) o Mass of tissue that grows abnormally and has no physiological function o Most originate in glial cells and white matter tissue o Classified as either benign or malignant o Location and prognosis is a primary concern o 3 major types of tumors identified by location  Glioma – abnormal production of glial cells  Meningioma – originate in the meninges  Metastatic tumors – originate in non-cerebral structures (lungs, skin, breasts)  Degenerative and Infectious Disorders o Degenerative disorders have been associated with genetic aberrations and environmental aspects o Example of degenerative disease = Huntington’s Disease o Causes of Parkinson’s disease are not unknown but it is suspected that the cell death in the dopaminergic neurons may be accelerated by unknown toxins accumulating in the environment o Cause of Alzheimer’s disease is hypothesized to be a production of an amyloid protein going awry and leading to the characteristics of plaque found in the brains of patients with the disease o Progressive neurological disorders can also be caused by viruses  HIV that causes AIDS-related dementia has a tendency to lodge in subcortical regions of the brain, producing diffuse lesions of white matter by destroying axonal fibers  Herpes simplex virus destroys neurons in cortical and limbic structures if it migrates to the brain  Viral infection is also suspected in multiple sclerosis (incidence of MS is highest
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