lecture_notes_fall2011_part2 - KIN 3E03 /Life Sciences 3K03...

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Unformatted text preview: KIN 3E03 /Life Sciences 3K03 Neural control of human movement Dr. Ramesh Balasubramaniam Fall 2011 NOTES Unit 2 Overview of concepts Movement Neurophysiology Perceptually guided action Dorsal & Ventral streams Vision for recognition; Vision for action Parietal Lobe Pathologies: right: Neglect Left: Apraxia Movement planning Supplementary motor area Frontal lobe Fine tuning movements Cerebellum Basal Ganglia (dopamine regulation) Projection to ? Motor programs & schemas (part three) Dopamine imbalance Too little dopamine = rigidity + tremor (Parkinson's disease) What happens when there is too much dopamine? you may see, hear or imagine things that are not real (SCHIZOPHRENIA) What is schizophrenia? Most common mental illness Affects about 1% of population Uniform rate throughout the world Adolescent onset Name derived by Bleuler (1911) from Greek; Schizo = split, phrenia = mind (not "split brain", e.g. severed CC) Intended to represent the split of the mind from reality Antipsychotic drugs Drugs that block Dopamine receptors reduce schizophrenic symptoms Drugs that block dopamine consequently have side effects similar to Parkinson's disease (symptoms of insufficient dopamine) Tardive Dyskinesia results from prolonged use of typical antischizophrenic drugs. Dyskinesia has some symptoms like Huntington's / Parkinson's Disease Highlighted here are neurons that make dopamine; Note their postsynaptic targets in the frontal cortex In frontal cortex, movement plans are triggered via dopaminergic neurons Also influences orbito-frontal cortex which can produce hallucinations/emotions Side Effects of Antipsychotic Drugs Wide range of side effects tremor, postural rigidity, cramps, Major problem is Tardive Dyskinesia Repetitive involuntary movements, especially face mouth and lips Irreversible result of long term blockade of dopamine receptors leading to supersensitivity Cells are taught not to respond/uptake dopamine, so when they do, they are hyper-sensitive to its effects. Tremor: Parkinsonian symptoms Symptoms of Schizophrenia Can be divided into two categories (Crow, 1991) Positive symptoms (seen as reflecting overactive brain function) Hallucinations Delusions Disorganised speech Disorganised behaviour Typically the kind of stuff you think about when you think of Schizophrenics More common in acute episodes Tend to respond to antipsychotics Symptoms #2 Negative symptoms (under-aroused brain function) Alogia (loss of fluency in thought & speech) (loss of logical process) Akathisia (inability to sit still) (loss of ability to keep still) Affective blunting (Loss of fluency of emotional expression) Anhedonia ( absence of pleasure or ability to feel it) (no pleasure) Avolition (absence of drive) Catatonia (excessive immobility) Akathisia (inability to sit still) Back to Basic neurophysiology What are lesions? Why do people have strokes? How does the brain get damaged? Scope for recovery (Later half of the course). from carotid to cervical to middle cerebral artery (MCA) Strokes generally happen in the cortical branches of the MCA - Irrigates the occipital lobe W. W. Norton W. W. Norton From greek for 'blood restricting' ISCHEMIC STROKE - BLOCKAGE GENERAL: As a result of a break or infarct in a brain region, the cells in that area begin to undergo necrosis. Other ruptures generally follow (comorbidities). Who gets it? Ischemic stroke is by far the most common kind of stroke, accounting for about 88% of all strokes. Stroke can affect people of all ages, including children. Many people with ischemic strokes are older (60 or more years old) (takes time to build up blockage in arteries) An ischemic stroke occurs when an artery in the brain becomes blocked. Can also occur pre-natally due to smoking during pregnancy. INTRACEREBRAL HAEMORRHAGE - RUPTURE AND LEAK Intracerebral hemorrhage usually occurs in selected parts of the brain, including the basal ganglia, cerebellum, brainstem, or cortex. Occurs at all ages. Generally initiated by blunt force trauma. A ruptured blood vessel will leak blood into the brain, eventually causing the brain to compress due to the added amount of fluid. Subarachnoid Haemorrhage Sub-arachnoid haemorrhage occurs when a blood vessel just outside the brain ruptures.The area of the skull surrounding the brain (the subarachnoid space) rapidly fills with blood. Who gets it? They may develop from birth or in childhood and grow very slowly. Some people have not one, but several aneuryms. Subarachnoid haemorrhage can occur at any age, including teenagers and young adults. Surgical treatment of aneurysms involves placing clip on neck of aneurysm. . Middle cerebral artery infarction The middle cerebral artery (MCA) is by far the largest of the cerebral arteries and is the vessel most commonly affected by cerebro-vascular accidents (CVA) or stroke. The MCA supplies most of the outer convex brain surface, nearly all the basal ganglia, and the posterior and anterior internal capsule. Infarctions that occur within the vast distribution of this vessel lead to diverse neurological problems. MCA stroke describes the sudden onset of focal neurological deficit resulting from brain infarction or ischemia in the territory supplied by the MCA. Treatment: blood thinners OR coagulants (depends) to either prevent clotting or to initiate clotting to prevent spread One more time... Basal ganglia function: dopamine in excess produces schizophrenia Basic structure of a stroke (infarction of cerebral arteries) Lateralization and hemispheric differences Split brain patients. Recap Dopamine imbalances Antipsychotic drugs Structure of a stroke and lesions Today: hemispheric differences/cerebral lateralization. Cerebral lateralization We've seen the brain from the front to back (frontal to occipital) But what's happening in the two hemispheres? Are they different? Why so? area of premotor cortex (M6) Central Sulcus Notice that the sylvian fissure looks different on either side (hooks up in right hemi) This is because synaptic connections on either side are remarkably different. Homotopic: same spot, opposing hemisphere Heterotopic: different spot, opposing hemisphere (e.g. in Apraxia where LEFT parietal lobe sends action representation information to the RIGHT motor cortical areas as well) Ipsilateral: different spot, same hemisphere Split-brain patients Sectioning of corpus callosum as a treatment for medically intractable epilepsy This procedure is called callosotomy. Can study the separate contributions of the left and right hemispheres to various abilities/tasks No inter-hemispheric inhibition. Split-brain patients Sectioning of corpus callosum as a treatment for medically intractable epilepsy This procedure is called callosotomy. Can study the separate contributions of the left and right hemispheres to various abilities/tasks "Split-brain" can be induced surgically by injecting Sodium Amytal (a barbiturate) into one carotid artery temporarily (5-10min) puts half the brain to sleep allowing neurologists to assess function in the awake hemisphere Sometimes the affected hemisphere is removed entirely (hemispherectomy) - where the remaining hemisphere takes over for functions of the old one (neural plasticity!) Put the left side (language) to sleep W. W. Norton W. W. Norton The right side knows what the object is, but the left side was asleep, so it has no recollection. There would be no problem if the stimulus were to be presented to the right side. OBJECT AGNOSIA Result of the speech system being anaesthetized. Patient cannot name the object but can point to it. W. W. Norton Split Brains Cross hemispheric communication How does the brain control the movement of two limbs (each controlled by different hemispheres). Movement interference Consider patting your head and rubbing you belly. Bimanual coordination Bringing two limbs together Unimanual movements: activation of primary motor cortex, cerebellum, basal ganglia. Bimanual movements are much more complex: involves neural crosstalk across the corpus callosum Experiment. While sitting at your desk, lift your right foot off the floor and make clockwise circles with it. Now, while doing this, draw the number "6" in the air with your right hand. Your foot will change direction!!! Movement interference: non-symmetrical movements are extremely difficult due to interference via the CC No CC = no interference = no problem Movements (fingers) return to in-phase movement Movements can also undergo IPSILATERAL interference (same side) This shows that the body prefers homologous muscle group activation (the brain prefers to send similar population vector commands so it automatically switches over when the motion becomes too taxing) Principles of bimanual coordination Inphase movements are much more stable Movements that involve homologous muscle groups are more stable Movement destabilizes at high speeds or switches to a new pattern Like Horses: walk, trot, gallop. Frontal lobe lesions SMA/PMC lesions causes serious bimanual coordination problems. Actions are represented in many different ways in the frontal lobe (body-based, environment-based and task-based). Anarchic hand aka. Dr. Strangelove syndrome Caused by huge lesions in the frontal lobe. Hand seems to act with a mind of its own Patients do not feel that the hand is not part of their body (not controlled by aliens) Exhibits orderly goal-directed behavior when normal. This leads to improper communication between the SMA/PMC and the motor cortex. "One evening we took our patient, Mrs GP, to dinner with her family. We were discussing the implication of her medical condition for her and her relatives, when, out of the blue, much to her dismay we saw her left hand taking some leftover fish-bones and putting them into her mouth". "She was abashed by what she did, though a little later, while she was begging it not to embarrass her anymore, her mischievous hand grabbed the ice-cream that her brother was licking". "Her right hand immediately intervened to put things in place and as a result of the fighting the dessert dropped on the floor. She apologised profusely for this behaviour that she attributed to her hand's disobedience. Indeed she claimed that her hand had a mind of its own and often did whatever "pleased it" ". "[the] left hand would tenaciously grope for and grasp any nearby object, pick and pull at her clothes, and even grasp her throat during sleep... She slept with the arm tied to prevent nocturnal misbehavior. She never denied that her left hand and arm belonged to her, although she did refer to her limb as though it were an autonomous entity." One more time... Structure of a stroke/lesion Split brain experiments Cerebral lateralization and bimanual coordination Frontal lobe lesions and the alien hand syndrome Language & Speech production Is a movement control issue Coordination and co-articulation (remember TULIP) Aphasia: due to damage to speech areas arcuate fasciculus connects brocas and wernicke's areas Broca's aphasia: Serious lack of fluency and grammatical problems Sits right below the ventral premotor cortex (below the SMA) Wernicke's aphasia: Severe Auditory Comprehension Deficits Speech Output Rapid (Fluent) But Often Meaningless Clinically classified varieties of aphasia. Broca's & Wernicke's Aphasia (Non-Fluent vs. Fluent Speech) Conduction Aphasia (Fluent, Good Comprehension Poor Repetition) Anomia (Fluent, Good Comprehension/ Repetition, Poor Naming) Damage To The Angular Gyrus & Inferior Parietal Lobe (basically, the left parietal lobe = names) Global Aphasia (Non-fluent, Poor Comprehension/ Repetition etc.) Extensive Damage To Fronto-Temporal-Parietal Lobes Finally, Foreign accent syndrome: Play video http://news.bbc.co.uk/media/video/39522000/rm/_39522150_accent05_twigg_vi.ram Cookie Theft - Non-fluent Speech Broca's Aphasia - "Red..Red..Water and the plate and I got there and nnn. Wash the plate and she wash it and she dry it and the pay...paylot....and that's the boy and there and he want and he want a stat the boy sig down here (points at stool) and he koot and he what there koot jar, and the girl the girl and the water" (JT: so what's happening with the boy then?) "Yes, she got the boy fall yes,on the floor and the water right in her in her in her in her.... (JT: what about the girl?) she laughter, laughter yes because the girl yes kooken yea" (PW laughs) Broca's Aphasia Severely Non-fluent (Responses: "Yes" "No" etc.) Production Reduced In Grammatical Complexity Poor Articulation (Dysarthria) Poor Melodic Line (Dysprosody) Can't keep a melody Poor Speech Volume (Hypophonia) Can't maintain tone HOMER SEE HOMER DO: Motor theory of speech perception. Strong evidence for mirror neurons being active during speech Areas with mirror neurons: perception - Ventral premotor cortex (near Broca's) Shown by Iacoboni et al at UCLA. - Superior temporal sulcus - Inferior parietal area (near Wernicke's) Cookie Theft - Fluent Speech Wernicke's Aphasia "Well this is... mother is away here working her work out here to get her better, but when she's looking, the two boys looking in the other part. One their small tile into her time here. She's working another time because she's getting to. So two boys work together and one is sneakin' around here, making his work an' his further his time he had." Wernicke's aphasia Severe Auditory Comprehension Deficits Speech Output Rapid (Fluent) But Often Meaningless Phonemic (STOOL - "Pool") Semantic (STOOL - "Chair") Hard time being specific/meaningful Neologisms (STOOL - "Gwool") "Bullshit words" Universals of Language Raise a Japanese baby in Mississippi and s/he'll learn a Southern drawl and all other mannerisms from South Semanticity Language conveys meaning Arbitrariness No inherent connection between symbols/sounds and meaning in brain e.g., origins of letter "A" or WERNICKE'S COMES FIRST 1. Auditory cortex 2. Wernicke's area - analysis of sound, determines the word 3. Transmitted to Broca's area via arcuate fasciculus 4. Broca's area - forms a motor plan to repeat the word, sends to motor cortex 5. Motor cortex manipulates larynx to say the word Evidence reflecting pre-motor planning: speech errors Common examples Substitution Anymay (Anyway) Exchange emeny (enemy) Shift highvway driwing Addition the plublicity (publicity) Omission sonata _umber ten (number) "OASES" - evidence of pre-motor plans: Omission, Addition, Substitution, Exchange, Shift Differences between speech and other movements In speech, there are very few clear-cut agonist-antagonist muscle groups Only one articulator, the mandible, has the kind of joint that plays a prominent role in other types of studied movements Tongue and facial muscles have relatively few spindles proprioception has to be mediated by other kinds of sensory receptors Sensorimotor neural pathways are among the shortest in the body: fast conduction times and presumably short processing times for feedback control involving peripheral sensation Speech is a generative process, with an internally constructed plan and relatively little physical interaction with the environment Speech is: super fast, has a huge amount of degrees of freedom in movement What is the number of degrees of freedom to be controlled? Velum Lips Tongue blade Tongue body Consider the movements of each of these structures Approximate number of muscle pairs that move the Mandible Hyoid bone Tongue: 9 Lips and hyoid bone Velum: 3 have the most DoF based on # Lips: 12 of muscle groups. Mandible: 7 Hyoid bone: 10 Larynx: 8 Pharynx: 4 muscles of the respiratory system There are also: Larynx Implication: The number of degrees of freedom that have to be controlled in speech is large and the control problem seems immensely complicated Sentences Phrases Words Morphemes Phonemes Phonemes Phonemes are the smallest significant units of sound in a language. Perception of speech involves mirror neuron deconstruction of bilabial gestures What's involved is changing the column of moving air. /p, b/ Bilabial Plosives (explosive sound) /s, z/ Fricatives (based on friction Difference between p and b as well as between s and z is voicing (vibration of vocal cords). Onset of voicing is responsible for difference between pa and ba. The respiratory system most massive (slowly-moving structures) Provides energy for sound production Fluctuations to help emphasis Different patterns of respiration: breathing, reading aloud, spontaneous, counting Different muscles are active at different phases of the respiratory cycle a complex, low-level motor program Consonants Place of articulation: where disruption of airflow takes place Manner of articulation: how disruption takes place Voicing: When vocal chords begin to vibrate Vowels Placement in mouth: front, center, black Tongue position: high, middle, low Other speech control systems Larynx Smallest structures, most rapidly contracting muscles Voicing, turned on and off segment-by-segment Vocal tract Intermediate-sized, slowly moving structures: tongue, lips, velum, mandible Can produce sounds at rates up to 15/sec To do so, the movements are coarticulated (TULIP) Controlled by high-level motor programming (frontal areas). Auditory probably not used very much. What kind of information is used by the brain to regulate speech? McGurk Effect: Speech is special because it involves both audio and visual processing elements, including motor processing Processing times would be too long Some of the movement toward vowel targets occurs during consonants, when little or no sound is generated Orosensory (somatosensory) feedback: Muscle tension (tendon organs) and length (spindles), joint (TMJ) position receptors, surface contact pressure Could be particularly useful for achieving consonant targets Is Language uniquely human? Yes. Atleast syntax generation is. Ability to arrange the symbols in a structured way. Generate an infinite number of combinations There is an infinite of symbols from a few number of symbol combos (nouns, The problem of projective predication. verbs) from only a set few Even Sign language has this "generative" property (every SL is different). Meet Nim Chimpsky Nim Chimpsky with psychologist Laura Ann Petitto. Petitto was his caretaker and sign language tutor. At Columbia University, Herbert Terrace designed the program to teach Nim sign language. After years of work and videotape analysis of Nim's conversations, Terrace found that when Nim combined symbols into longer sequences, he was either imitating his trainer's previous signs, or "running on" with his hands until he got what he wanted (e.g., "eat Nim eat" or "play me Nim play". Moreover, Nim signed spontaneously only when he wanted something whereas humans use language in a more diverse way. That animals use symbolic communication is probably true. But there is no evidence that their language is Structured or Generative. Fundamentally non-spontaneous unless desire is associated Evolutionary Reasons? Horse, sheep, human and dog Notice the horse's huge ass brainstem (why? lots of lower-level motor control/movement) Evolution Animal phyla Human evolution Increase in brain size Encephalization quotient Humans have the largest relative brain to body size ratio. One more time... Language disorders: Aphasia Frontal lobe and speech motor planning Mechanisms of speed production How to record from da brain Some basics about neuronal functioning 1)Neuron structure 2)Neural communication: neural transmitters 3)Ensemble neural activity. The Anatomy of a Neuron cell body (or soma), dendrites, axon All components (ER, GA, Mitos, Ribos, etc.) are present in neurons Neuron Physiology neurons perform computations, they transform information. the functional components of a neuron. an input component (dendrites) an integration component (axon hillock) a transmission component (axon) an output component (synapse) Dendrites receive input, then the axon hillock integrates the info allowing for the axon to transmit it to an output synapse Active conductance = changes to signal passive vs. active conductance electrical vs. chemical transmission Neurons convert chemical (NT) to electrical activity The Synapse Axon terminal releases neurotransmitters Neurotransmitters cross the synapse and bind to receptors on another neuron Neurotransmitters released, taken up again by first neuron The synapse itself is entirely electrical. Sending information is a chemical process (crossing the synapse). Neural Communication Neural messages reflect membrane potential changes A cell excited (stimulated) from its resting potential state fires an ACTION POTENTIAL release neural message The neural message => Neurotransmission from one neuron to another neuron across a synapse. Action Potentials Action Potential Involves the action of voltage-gated channels Massive, rapid exchanges of ions in and out of the cell Na-K pump boots out 3 Na+, brings in 2 K+ Action Potentials How neurons transfer information Changes neuron's membrane potential Rising phase membrane depolarizes Becomes +ve Overshoot Falling phase membrane repolarizes Becomes -ve again Undershoot Restoration of resting potential The Propagation of Action Potential Long-distance traveling: Eg. from the motor cortex to the spinal cord of giraffe. Loss-free and Fast The natural solution: myelination regeneration Oligodentrocytes (CNS) Schwann cells (PNS) Synaptic Transmission When an action potential reaches the terminal button, synaptic vesicles release neurotransmitter (NT) into the synaptic cleft NT diffuses over the cleft At least three possible scenarios after this: 1 2 3 NT molecules do not attach to a postsynaptic receptor NT released in an area with no immediate receptors NT "keys into" a receptor site The latter scenario leads to change in the ionic permeability of the postsynaptic membrane Excitatory postsynaptic potential (EPSP) Inhibitory postsynaptic potential (IPSP) Neuronal Interaction Chemical synapses and neurotransmitters Synapses: the contact sites between neurons Pre- and post- synaptic neurons Action potential triggers the release of neurotransmitter Neurotransmitters drift across the synaptic cleft Neurotransmitter-gated channels open, generating electrical current (or postsynaptic potential (PSP)) Dependent on the sign of PSP, synapses are clarified as excitatory and inhibitory ones. Neurotransmitters (NT) Probably 100's Neurons often classified by the NT it releases Effect of NT depends on nature of receptor site Glutamate was the first NT to have EVOLVED in humans; Glutamate is converted to GABA (both amino acid NTs). Class Glutamate is converted into GABA First to be DISCOVERED in the lab Examples Glutamate Excitatory GABA Inhibitory Acetylcholine Serotonin Dopamine Norepinephrine Epinephrine Adenosine Nitric Oxide (NO) Endorphins Amino Acids Acetylcholine Monoamines Dopamine is converted into norepi which is converted into into epinephrine Purines Gases Peptides Neurotransmitters ... Basic Concepts Biosynthesis: All NT - synthesized in the cell General role of NT: Different NT seem to be important for different aspects of behaviour Many drugs that affect behaviour and experience do so by their effects on synaptic transmitters or on receptors Glutamate - Possibly, among the first NT type to have evolved - Principal excitatory NT in the brain - Produced in abundance in cells - Biosynthesis: ketaglutarate amino transferase glutamate - Stored in synaptic vesicles released at terminal buttons Gamma Amino-Butyric acid (GABA) Principal inhibitory NT in the brain - Produced in cells that contain glutamic acid decarboxylase - Biosynthesis: glutamate glutamic acid decarboxylase GABA -Stored in synaptic vesicles released at terminal buttons - Responsible for most of inhibitory information transmitted - Most neurons receive GABA types of input - Alcohol facilitates (agonist) GABA receptors Hence inhibitory effects on neurons Acetylcholine (ACh) First neurotransmitter discovered Generally Facilitative Effects Biosynthesis in the cell Functions in muscular contractions Secreted by efferent axons at muscular junctions - Initiates all voluntary actions The Black widow spider (Latrodectus) and Cottonmouth are so toxic because they trigger massive release of acetylcholine from neurons. e.g. Kill Bill Volume 2 CURARE counters the effects of ACh in NICOTINIC receptors ACh ATROPINE counters the effects of ACh in MUSCARINIC receptors ACh acts on two different types of post synaptic receptors: Nicotinic receptors found at neuromuscular junction of skeletal (only) muscles, on post-ganglion neurons of the parasympathetic nervous system, and on many neurons in the brain (e.g. in the hippocampus). nicotine is an agonist of Ach activity (activates - facilitates muscle movement) curare is an antagonist (hence its ability to paralyze skeletal muscles) Muscle receptors (muscarinic) found at neuromuscular junctions of cardiac and smooth muscle and on glands, On post-ganglion neurons of the sympathetic nervous system. muscarine (a toxin of certain mushrooms) is an agonist. atropine is an antagonist (its use in acetylcholinesterase poisoning) Catecholamines - Two important catecholamines: - Dopamine (DA) Norepinephrine (NE) Produce both inhibitory and excitatory post synaptic potentials depending on the receptor Essential function of catecholamines is to mobilize - Stored in synaptic vesicles released at terminal buttons ...like all the rest (except for ACh). Another major circuit is the thalamocortical system? DA Involved in the control of movements Major DA Circuits & Nuclei The nigrostriatal system SN to NEOstriatum DA nuclei in the substantia nigra (SN). as seen in degeneration in Parkinson's SN -> striatum of the basal ganglia Dopamine circuits primarily found in the basal ganglia. Cocaine- a strong reuptake inhibitor of dopamine 1. chronic use=lose receptors in the postsynaptic membrane 2. block reuptake of dopamine= down regulation occurs and less receptors are available. 3. mood elevation is due to dopamine effects. Addictive drugs Nicotine, morphine, etc. Produce their effect by causing dopamine to be released. And dopamine can cause release of endocannabinoids (present in all neural systems). Glutamate and acetylcholine also initiate endocannabinoid synthesis and release. Indirect signalling causes release of more dopamine from the basal ganglia which lowers the threshold at receptors. Norepinephrine Involved in attention and readiness to act; involved in the alarm Fight or flight reaction (a-k-a adrenalin) Transmitted to almost every brain region Major cell bodies located in locus coeruleus of the pons, medulla, and thalamus Locus Coeruleus (in PONS), MEDULLA, THALAMUS all have high norepi cell body density. (PMT?) Indoleamine: Serotonin Major (5HT) Functions: regulation of mood and pain; involved in eating, dreaming, and arousal vividness of dreams Cell nuclei located in the raphe nucleus in brain stem Raphe nucleus -> cerebral cortex, basal ganglia, dentate gyrus of hippocampus LSD interacts with the 5HT transmission; LSD alters visual perceptions Overview of Serotonin Serotonin (5-hydroxytryptamine, or 5HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system. The functions of serotonin are numerous and appear to involve control of appetite, sleep, memory and learning, temperature regulation, mood, behavior (including sexual), cardiovascular function, muscle contraction, endocrine regulation, and depression Serotonin (5HT) Biosynthesis Tryptophan -> 5-HTP -> 5-HT Tryptophan (an dietary amino acid) tyrosine hydroxylase 5-hydroxytryptopahn (5-HTP) 5HT decarboxylase 5HT (5-hydroxytryptamine) Tryptophan (an dietary amino acid) -> obtained from bananas, corn, meats (turkey), Meals can alter synthesis of 5HT: chocolate and sugars boost up synthesis of 5HT Reward mechanisms in thalamus Cerebellum and visual cortex Made in the Made in the - Goes everywhere How do Neurons compute? By changing conduction and ion potentials. Made possible by Neurotransmitters. Strengthening and weakening of synapses (Hebbian learning rule). - Synapses used often strengthen, synapses seldomly used weaken Strengthening synapses Synapses used often are strengthened (A) Those not used are weakened and can become ineffective (B) Used lots A Strengthening (more receptors, more transmission) B Not Used Weakening (less receptors/uptake) Neurons that fire together, wire together Learning Rule: When two connected neurons are both excited, the connection between them is strengthened x 1(t) x 2(t) w 2 w1 n axon y(t+1) w xn(t) Single-Cell Recording Electrical activity of a neuron is recorded via electrode implanted near the cell (sometimes inside the cell see fig). Only feasible in animals or special cases where human brain surgery is involved. Multi-cell recording is possible via array of microelectrodes. Computer programs separate signals from different neurons. Rate coding: the number of action potentials is important (e.g. 40 spikes/sec). Spike coding: the timing of each action potentials is important (e.g. spike #1 occurred at 0.52 msec). Excellent temporal resolution, but limited to a few neurons. Rate = how many Timing = how often Important non-invasive techniques EEG: electroencephalography MEG: magnetoencephalography MRI: magnetic resonance imaging (structural and functional aka fMRI). Positron emission tomography (PET) Transcranial magnetic stimulation (TMS) Electroencephalograp hy EEG Quantity measured: electric potential on the scalp surface Order of magnitude: 20uV Temporal Resolution: ms Spatial Resolution: cm Cost: cheap Advantage: easy to record Disadvantage: signals get smeared before they reach the scalp fast smeared EEG Cinically useful as distinct brain states show characteristic EEG signal EEG Normal Activity Seizure Activity Cinically useful in determining the focus of epileptic seizure EEG "Event-related Potentials" Background EEG signal can be removed by trial-averaging revealing the response of a brain region to stimuli Event-Related Potentials (ERPs) Changes in the EEG signal that are correlated with a discrete sensory stimulus (e.g. a light turning on). ERPs difficult to detect because they are weak and embedded in noise -> averaging needed. Peaks and troughs in the ERP waveform associated with different stages of processing (e.g. early sensory stages vs. later cognitive stages). Evolution of the ERP wave through the brain over space and time shows processing pathways. SQID = Superconducting Quantum Interference Devices Magnetoencephalograph y MEG Quantity measured: components of the magnetic field Order of magnitude: 100fT Temporal Resolution: ms Spatial Resolution: cm Cost: expensive Advantage: Clean signals Disadvantage: Insensitive to radial currents fast pretty clear Magnetic field on subject's head and in polar projection BLUE = inhibition, RED = excitation (visualization of activity) Magnetic Resonance Imaging: MRI Quantity measured: `water content'of the brain tissue Knowledge gained: brain structure Temporal Resolution: min Spatial Resolution: mm very clear pretty slow Cost: expensive Advantage: 3D-volume resolution Disadvantage: no functional or temporal information Using the gray-white matter boundary as an anatomical constraint Stereotaxic Image-guided Tumor Resection System (SIGS) used to isolate tumors and repair aneurysms MRI vs. fMRI MRI studies brain anatomy. Functional MRI (fMRI) studies brain function. BOLD (Blood Oxygenated Level Dependent signal) measures changes in magnetic field based on decay time Functional Magnetic Resonance Imaging: fMRI Quantity measured: ratio between oxy- and deoxyhemoglobin Knowledge gained: activated areas Temporal based on ratios of O2 Resolution: sec saturation oxygenated haemoglobin is FERROMAGNETIC Spatial Resolution: mm Cost: expensive poor temporal (slow) good spatial Advantage: 3D-volume resolution Disadvantage: low temporal resolution, no straight forward analysis How powerful is this magnet About 250,000 more poweful than the earth's magnetic field. fMRI Setup fMRI Experiment Stages: Prep 3 stages: prep, shimming (adjustment), sagittals 1) Prepare subject Consent form Safety screening Instructions 2) Shimming putting body in magnetic field makes it non-uniform adjust 3 orthogonal weak magnets to make magnetic field as homogenous as possible 3) Sagittals Note: midline to use to plan Take images along theThat's one g, two t's slices Multiple sagittal slices used to create visualization 4) Take anatomical (T1) images high-resolution images (e.g., 1x1x2.5 mm) fMRI Experiment Stages: Anatomicals 3D data: 3 spatial dimensions, sampled at one point in time 64 anatomical slices takes ~5 minutes Slice Terminology Slice Thickness e.g., 6 mm VOXEL (Volumetric Pixel) In-plane resolution e.g., 192 mm / 64 = 3 mm 3 mm 3 mm SAGITTAL SLICE Number of Slices e.g., 10 6 mm IN-PLANE SLICE Matrix Size e.g., 64 x 64 Field of View (FOV) e.g., 19.2 cm IMAGINATION vs EXECUTION OF MOVEMENTS Execution Imagination X, Y, Z coordinates where + is further to cortical surface and - is deeper below During imagination the SMA was active Actions synchronized to music revealed activation in auditory cortex, basal ganglia, thalamus and cerebellum These same areas activated during syncopian (jazz-like) activity but in much higher rates Functional MRI Takes advantage of the fact that neural activity is followed by blood flow in a highly predictable manner Altered blood flow alters RF signal from active brain regions Functional MRI Permits examination of brain regions that become active during cognitive performance cognitive task baseline Facilitates comparison of brain activity in different population Functional MRI Primary visual cortex implicated during movement and static Area (visual cortex) MT processes MOTION specific information (not active when object is static) Analysis methods take advantage of known hemodynamic properties of the brain Magnetic Resonance Spectroscopy (MRS) Standard fMRI is tuned to the resonance frequency of hydrogen (component of water). MRI can be tuned to the resonance frequency of other chemicals (e.g. creatin -> label for neuron -> diagnosis of cell loss; choline -> precursor of ACh). Hasn't been done in humans yet due to risk factors Transcranial Magnetic Stimulation Steps to TMS: 1) Isolate areas 2) Target coil to area using stereotactic techniques 3) Perform somatotopic experiments More stimulation of isolated areas reveals greater proportion incorrect (more cognitive failure) These techniques can be used to test for CORTICOSPINAL damage Coil placed over target brain region Cognitive failures recorded Transcranial Magnetic Stimulation (TMS) Focused oscillating magnetic fields can activate or suppress neural activity across the skull. (scary shit) Pluses and minuses: Noninvasive. Allows direct manipulation of neural (can stimulate activity. dopaminergic Used as therapy for depression. neurons in SN) Single pulses affect brain activity for only a few seconds. Repeated pulses can change brain activity for weeks. Really scary. Positron Emission Tomography Type of tracer determines type of activity detected 15O radioactive oxygen, is injected into bloodstream with water Measures blood flow Radioactive Sugar Measures metabolism Alternative to fMRI, but is worse at detecting changes Positron-Emission Tomography (PET) Subject injected with radioactive substance into blood-stream. Radioactive substance flows to brain regions that are more active. Several substances can have radioactive labels (e.g. sugars, neurotransmitters). Doughnut-shaped camera that records radiation and reconstructs 3D model of radioactive source. PET images blood flow, not neural activity directly. Radioactive labels have short half-life and are rather safe. One more time... Neurons & Neurotransmitters Single Neuron recordings EEG/MEG/MRI/PET MRI vs fMRI TMS and related techniques ...
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