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Central Nervous System Higher functions Electroencephalography Recording of electrical activity of the brain by placing electrodes on scalp is Electroencephalography Recording of electrical activity of the brain by placing electrodes on the brain surface is known as Electrocorticography First recording was done by Hans Berger Physiological basis of EEG recording Cerebral cortex has 6 layers (superficially layer 1 to the deepest 6th layer) Cell bodies of neurons are present in deep layers. 1st layer has very few cell bodies, instead it consists of dendrites of other neurons which synapse with axons of neurons from other areas especially from nonspecific thalamic nuclei. Since we record EEG from the surface, EEG electrodes pick up electrical activity from the area which is near the electrodes i.e from the superficial area of cortex having dendrites. At dendrites, potential change occurs only as graded potentials i.e EPSP and IPSP, due to the synapses. Hence, Fundamentally, EEG electrodes don't pick up action potential and the electrical activity recorded by these electrodes is a sum of all excitatory and inhibitory postsynaptic potentials. Also, if any activity is near the electrode, the effect of that activity will be recorded more than that of an activity far from electrode. Physiological basis of EEG recording ScALP. EEG dectodaa m \ oe peak Epse+ IPsP om dendn tea Sop ys A. 2 3 Com 4 Ss 6 sy oat Synchronized and desynchronised EEG activity Neurons from thalamus make contact with the dendrites in the superficial layer of the cortex. The way these projections from nonspecific thalamic nuclei activate the cortex affects the EEG. More the cerebral activation by nonspecific thalamic nuclei , more is the frequency of EEG waves (desynchronised activity) Synchronized EEG activity: Amplitude of EEG waves is more while frequency is lesser (delta waves - the most synchronised wave occurs even if thalamus connections are removed i.e no activation from thalamus leads to more synchronisation) Desynchronized EEG activity: desynchronised activation of cortex, occurs in awake and alert state - In this case, EEG waves amplitude is less but frequency is more Some hypothetical examples of synchronised and desynchronised EEG activity due to summing up of EPSPs and IPSPs EEG waves are most desynchronised in awake and alert state. The activity changes to more and more Basis of EEG waves eaearenaatina moe Ni EPSPs Excitation of different neurons - at same time IIVV\ Geezea waves in EEG ih INN NVA Synchronized - High amplitude , Low frequency — [WN IVY Excitation of different neurons ~ at different time ers (VN re AAN/ Desynchronized ~ Low amplitude, High frequency => synchronized as we become relaxed to drowsy and is most synchronized in deep sleep EEG waves In physiological conditions, four types of EEG waves are seen. From highest to lowest frequency, these are: 1. Beta waves — Highest frequency , EEG waves lowest amplitude Beta waves seen in awake, alert. and when concentrating ‘More in frontal cor 2. Alpha waves Renpte, Leas ia (= Berger's waves) seen in awake ard relaxed scove More in occipital and parietal cortex 3. Theta waves Wap www #7 #8 Seen in children, emotional disturbance 4. Delta waves - he . <3 Hz Lowest frequency, dal Seen in deep sleep chroixed highest amplitude (Remember as BATD) 13-30 Hz Alert, awake — Frontal and state parietal regions In awake but Occipital 8-13 Hz 50-100 KV relaxed state regions , also from parietal regions In chidden, Parietal and = 3-7 Hz >100 nV emotional Temporal disturbance in region adults In infancy, <3 Hz >100 WV deep sleep, under general anaesthesia, comatose state Central Nervous System Higher functions Physiology of sleep Definition Sleep is an unconsciousness state with 1.Decreased motor activity 2.Decreased response to stimulation 3.Stereotypic postures (in humans, lying down & eyes closed) 4.Relatively easy reversibility (distinguishing it from coma, hibernation) Based on polysomnographic recordings (recordings made during sleep using EEG, EMG and EOG), it has been found that sleep consists of two alternating phases 1. NREM sleep (= Slow wave sleep) which itself consists of 4 stages Stage 1 Stage 2 Stage 3 Stage 4 NREM stands for Non Rapid Eye Movements sleep (no eye movements during this phase) 2. REM sleep - Named such since Rapid Eye Movements (REM) occur during this phase of sleep Wakefulness Stage 1 Sleep wake cycle — NREM Stage 2 REM Stage 3 Stage 4 Pattern of sleep progressively progress to stage 4. Then again progressively move to stage 1 and then to REM sleep. This pattern of sleep repeats throughout sleep (90 minutes of NREM followed by 5-30 minutes of REM phase) Sleep pattern EM stage 12243+4934241 —>REM Sleep pattern With successive cycles, duration of Stage 3 and 4 NREM decreases and duration of REM phase increases Variation with age Duration: 17-18 hours at birth but the sleep is interrupted and occurs in phases Continuous sleep is established by age 4 Duration of sleep is up to 7-8 hours by age 20 REM sleep occupies 80% of total sleep time in premature infants, 50% in full-term neonates, 25% in adults, 20% in elderly Characteristics of REM and NREM sleep Complete loss of muscle tone (except eye muscles, diaphragm and stapedius) Normal Rapid eye movements No eye movements High frequency, low amplitude Stage 1: Theta waves waves (just like in alert state. Stage 2: Theta waves That's why REM sleep is known aS interrupted by Sleep ama spinles (usd It also shows Pontogeniculo- waves), K complexes occipital (PGO) spikes - Large _(PiPhasic waves) phasic potential originating in Stage3 & 4: Delta waves” cholinergic neurons in pons, going _ (indicates marked to lateral geniculate body and then Synchronisation - hence to occipital cortex. known as Slow wave sleep) Increased brain activity with high metabolism metabolism Decreased brain Decreased responses to heat & cold Decreased metabolic rate Body temp drifts towards ambient temp Respiratory rate irregular, Respiratory rate less increased irregular heart rate Decreased sympathetic outflow and Increased parasympathetic outflow - hence decreased heart rate and BP Threshold for arousal with a sensory stimulus is more in REM sleep compared to NREM sleep. EEG in various phases of sleep beta waves Theta waves NREM = IW WY DW} AYA) PAW delta waves REM sleep ye rym remnant Beta like waves Functions of sleep 1. Metabolic-caloric balance: Sleep deprivation for long leads to loss of weight 2. Cognition: Deprivation of sleep leads to progressive malfunction of thought processes 3. Memory consolidation - and removal of unwanted information so that its not stores * Regeneration and repair and immune competence 5. Bedroom rehearsel for movements and thought processes- kind of mental imagery (in fact sometimes unsolved problems of awake state get solved during sleeping) a Related to neuronal maturation 7. Vent for suppressed/negative feelings (normally prefrontal cortex keeps limbic system inhibited in awake state. This inhibition is absent during sleep causing expression of emotional content much more during sleep) 8. Some role in temperature regulation Generation of sleep- Mechanism Increased neuronal activity during sleep causes accumulation of sleep promoting metabolite (adenosine). As sleep progresses, this metabolite is washed away again decreasing its concentration, promoting alert state Various nuclei are involved in maintaining awake and sleep state. These are: 1. Ascending reticular activating system (ARAS) neurons in brainstem 1. Norepinephrine secreting Locus cerulus (LC) 2. Serotonin secreting Dorsal raphe nucleus (DRN) 3. Acetylcholine secreting neurons of pedunculopontine (PPT) and laterodorsal tegmental nucleus (LDT) ee eee 2. Hypothalamic neurons 1. Histaminergic neurons in tuberomamillary nucleus (TMN) of Posterior hypothalamus 2. GABA secreting neurons of ventrolateral optic nucleus (VLPO) of anterior hypothalamus 3. Orexinergic neurons - secrete orexin (=hypocretin) 3. Basal forebrain - Acetylcholine secreting neurons Involved in wakefulness and REM All these neurons project to cortex and thalamus Different set of the above neurons are active during different states of consciousness i.e wakefulness, NREM sleep and REM sleep Wake promoting areas - active during wakefulness (Wake-ON neurons) Histaminergic neurons in posterior hypothalamus Norepinephrinergic neurons in locus coerulus in ARAS Serotonergic neurons in Dorsal raphe nucleus in ARAS Sleep promoting areas (active during sleep) VLPO has GABAergic neurons - active during NREM sleep (NREM-ON neurons) Lateral dorsal tegmental nucleus (LDT) and pedunculopontine tegmental nucleus ~ Release acetylcholine These are REM-ON neurons Wake-on REM-on neurons Central Nervous System Higher functions Thalamus Collection of neurons organized into large number of well defined nuclear masses. It is considered as (Except olfactory information) - Relays limbic, sensory and motor signals to the cerebral cortex Thalamic nuclei 1. Specific sensory nuclei - Ventrobasal nuclei (ventral posterolateral and ventral posteromedial nuclei - receive input from somatic sensations), lateral geniculate body (receives visual information), medial geniculate body (from auditory pathway) In turn projects to primary somatosensory areas of respective sensations (To layer IV of cerebral cortex) 2. Motor nuclei - Ventral anterior, Ventral lateral a. Basal ganglia and cerebellar output reaches to motor nuclei of thalamus which in turn projects to motor cortex. Role in initiation/ inhibition of movement b. The anterior nuclei receive input from the mammillary bodies and project to the limbic cortex to influence memory and emotion. 3. Association nuclei - Pulvinar Dorsal nucleus Receives information from cortex and projects back to association areas in cortex Role in interpreting the sensory information 4. Nonspecific nuclei —-Midline and intralaminar nuclei Receive information from reticular activating system Projects to cortex in diffuse manner (projects to all layers of cortex) Role in wakefulness (sleep -wake cycle) Central Nervous System Higher functions Hypothalamus Represents less than 1% brain mass Consists of large number of nuclei Located in lower part of brain, above pituitary gland Functions of hypothalamus Broadly: Visceral motor, somatic motor and neuroendocrine changes brought about by hypothalamus lead to appropriate behavioural responses. 1.Circadian rhythms 2.Regulation of sleep wake cycle 3.Endocrine functions 4.Regulation of water balance 5.Regulation of food intake 6.Regulation of behavior - emotional and reproductive (Appetitive behaviour = Thirst , hunger and sexual behaviour) 7.Autonomic control 8.Regulation of temperature Several body functions show ~ 24 h rhythm Suprachiasmatic nucleus of hypothalamus (endogenous biological clock) receives information about dark light cycle of environment from retinohypothalamic tract.This in turn effects the production of melatonin from pineal gland. Thus melatonin levels also show circadian rhythm for Increased melatonin promotes drowsiness and sleep. It is also responsible for diurnal variations in various secretions, cell activity and body temperature. Role of hypothalamus in circadian rhythm sunlight Darkness | | Silent Retinal ganglion cells | Activation of Retinal ganglion cells Decreased signal to Suprachiasmatic nucleus | Inhibits i ji Melatonin rropiatonsecrecon Melatonin mene Awake state Drowsiness and sleep Role of other hypothalamic nuclei in sleep wake cycle Wake promoting area - Tuberomamillary nucleus (Neurotransmitter: Histamine) And orexinergic neurons Sleep promoting area - Ventrolateral preoptic area in anterior hypothalamus (Neurotransmitter: GABA) (See pdf on physiology of sleep) i Releases releasing and inhibitory hormones which act on anterior pituitary controlling the release of hormones from anterior pituitary Interesting point The portal vessels arise from median eminence region of hypothalamus. This median eminence is outside the blood-brain barrier. Hence it is a strategic site to be in touch with various signals from the body. Thus the release of the hypothalamic hormones is linked with information from the body and hence in turn it can bring about changes in pituitary secretion depending on the body requirement. Gonadotropin releasing hormone (GnRH) Corticotropin releasing hormone (CRH) Stimulates LH and FSH secretion Stimulates ACTH secretion Thyrotropin releasing hormone (TRH) Growth hormone releasing hormone (GHRH) Stimulates TSH and prolactin secretion Stimulates growth hormone secretion Somatostatin Inhibits growth hormone secretion Prolactin inhibiting hormone (dopamine) Prolactin releasing hormone Inhibits prolactin secretion Stimulates prolactin secretion Oxytocin and Vasopressin (Antidiuretic hormone) are synthesised in paraventricular and supraoptic nucleus of hypothalamus and are transported to posterior pituitary by the axons. Oxytocin is important for uterine contraction during parturition and for milk ejection (Birth and nourishment) Vasopressin is important for regulation of water balance Hypothalamus regulates body water in two ways: 1. by creating the sensation of thirst, which makes the animal or person drink water, and 2. by controlling the excretion of water into the urine Regulation of water intake - two methods Hyperosmolarity Hypovolemia | Angiotensin I! Subfornical region and OVLT (organum vasculosum of lamina terminalis) | Increased water intake Decreased urinary volume (more water reabsorption) Hypothalamus has two centres for regulation food intake 1. Lateral hypothalamus (Feeding center) - inhibits Regulation of food intake food intake Satiety center —___» Feeding center 2. Medial hypothalamus (Satiety center) - inhibits Increase in glucose feeding center levels Intake of food The uptake of glucose in satiety center neurons is sensitive to insulin (this is in contrast to all other neurons) Fundamental In diabetes mellitus , the uptake of glucose in the neurons of satiety center is decreased. This decreases the activity of the neurons and they no longer inhibit feeding center. This is the reason for hyperphagia in diabetes mellitus Hypothalamus is principal outlet for effects of limbic system Stimulation of lateral hypothalamus leads to Rage and fighting behaviour, feeding and thirst Stimulation of Ventromedial nucleus leads to satiety, decreased eating, tranquility Thin zone of periventricular nuclei leads to reward and punishment reactions Sexual drive: Anterior and post hypothalamus Circuit involved include 1. Dorsal longitudinal fasciculus : From paraventricular nucleus to reticular formation in brainstem and dorsal motor nucleus of vagus. From reticular formation, it descends to the intermediolateral column of spinal cord affecting sympathetic neurons. 2. Medial forebrain bundle: Inputs from basal forebrain, limbic cortex and amygdala reach to hypothalamus via medial forebrain bundle. Visceral afferents from the nucleus of the solitary tract ascend from the brainstem into the hypothalamus by way of this bundle. From hypothalamus it descends like dorsal longitudinal fasciculus. Also, Anterior hypothalamus stimulation causes parasympathetic responses Posterior hypothalamus stimulation causes sympathetic hypothalamus Hence, Hypothalamus is important for Regulation of various visceral functions Anterior hypothalamus (preoptic area) - responds to heat - Heat loss mechanisms activated by anterior hypothalamus Cutaneous vasodilatation Sweating Posterior hypothalamus - responds to cold - Heat gain mechanisms activated by posterior hypothalamus Cutaneous vasoconstriction Release of catecholamines Shivering Integrated Physiology Temperature regulation Thermoregulation is important because body temperature affects the rates of cellular reactions. Hence maintenance of body temperature is very important for optimal functioning Body Temperature Shell temperature: Temperature closer to skin Changes depending on environmental temperature Core temperature: Temperature of “core” organs in cranial, thoracic and abdominal cavity. Core body temperature remains constant even with wide variations of environmental temperature (55°F-130°F) Core body temperature can be measured by - rectal temperature, tympanic membrane temperature, oral temperature Due to metabolic reactions, body generates lot of heat. Hence to maintain body temperature, it needs to achieve a balance between heat gained by metabolic reactions or by ambient temperature and heat loss occurring to environment. Mechanisms of heat transfer Radiation: Heat transfer from warmer to cooler object through electromagnetic waves traveling through space Conduction: Heat transfer from warmer to cooler object that is in direct contact with the warmer one. Transfer occurs through the movement of thermal energy from molecule to adjacent molecule Convection: Transfer of heat by air currents. Cool air warmed by the body (conduction) rises & is replaced by more cool air. Process enhanced by forced movement of air across body surface (e.g. fan causes movement of warmer air faster) Evaporation: Conversion of a liquid (sweat) into a gaseous vapor. Vaporisation requires heat, which is absorbed from the skin. What will the only way to loose body heat if environmental temperature is more than skin temperature? When environmental temperature is more than body temperature, body will gain heat from environment by conduction, and radiation. Also warm air could not be replaced by cooler air (except when we use external appliances) In such a case, body loses heat only by evaporation (sweating occur, the water takes up heat from the body and evaporates) Control system for temperature regulation Set-point: Reference temperature Hypothalamic Set point: 37°C (pre optic area) Thermal receptors: Present in skin and core regions (see below) Afferent nerves: carry the temperature information o hypothalamus Control center: Compares the afferent signal with set point. Depending on the difference, either heat gain or heat loss mechanisms are activated Efferent nerves: To skin (for vasodilation/vasoconstriction), and sweat glands, or muscle contraction ( for shivering) - depending on mechanisms activated Effector - skin blood vessels, muscle contraction, or sweat glands Integrating centre Reference Controlling system Controlled temperature Heat promoting center variable (Set Point) Heat conserving center (Temperature) Efferent and effectors Location: Core: Spinal cord, gut, great veins Shell: Skin TRPA 1 Cold < 18 c TRPM3, Cold <28 c TRPV 1 Hot 242 C & A delta TRPV 2 Hot ae A delta & beta TRPV 3 Hot 34-39 c Different thermoreceptors respond to a different range of temperatures with peak being at a particular temperature. The information reaches to hypothalamus and is compared with the set point. 5 0 15 20 % 30 35 40 45 50 55 60 “Temperature °C) In case of any deviation from set point, compensatory responses start to bring the temperature back to normal 1. Change in skin blood flow : Vasodilation for heat loss and vasoconstriction to prevent heat loss Increase in skin blood flow by vasodilation (by parasympathetic system - M3 receptors) cause heat loss to environment by convection and radiation. Decrease in skin blood flow by vasoconstriction (by sympathetic system - al and a2 receptors) prevents heat loss that could occur by convection and radiation). The thermoneutral zone is defined as the range of ambient temperatures where the body can maintain its core temperature solely through regulating dry heat loss, i.e., skin blood flow. Lewis-Hunting reaction - In “emperature oF injury : as one body areas excessive cold, vasoconstriction Prone Posy occurs. This leads to accumulation of ((ascconsscvon _] metabolites which cause local ‘Accumulation of . metabolites vasodilation (increased blood flow to Vasodilatation tissues). Once metabolites are | ape washed off, again vasoconstriction vasoconstriction vasodilatation occurs to prevent heat loss - aS ‘antinupus nutrient ard decreased blood flow. This alternating vasoconstriction and vasodilation prevents death of tissues due to ischemia caused by excessive vasoconstriction while preventing heat loos 2. Sweati for heat loss by evaporation Sweating only way to regulate body heat when environmental temperature > Core body temperature Sweat glands: eccrine glands with sympathetic cholinergic innervation 1g sweat removes 0.58 Calorie of heat Stimulation of central and . | ; peripheral cold receptors mechanism in chronic hot environment) | Motor centre for shivering (Posterior hypothalamus) Aldosterone ft Na absorption (adaptation 3. Shivering: for heat gain by increasing . Descending tracts muscle metabolism (Rubro and reticulospinal tracts) | Altemate contraction of agonist/antagonist muscle Can increase body heat production 4-5 times on i maximal shivering 7 heat generation 4. Non shivering thermogenesis 1. Due to t TRH from hypothalamus ~ Increased T3/T4 release from thyroid gland - Increased BMR - increased heat production 2. t epinephrine from adrenal medulla 3. Thermogenic effect of food Present in infants, disappears after puberty Constitutes 2% of body weight at birth Contains more mitochondria than white fat. Has Uncoupling protein (UCP-1) which uncouples oxidative phosphorylation. Hence energy of proton transfer by electron transport chain is released as heat instead of ATP production. It is under control of norepinephrine. Can produce 300 times more heat compared to normal tissue. Sites: Around core regions Summary of responses by control center Thermoregulatory center Anterior hypothalamus Posterior hypothalamus Heat-losing center Heat-promoting center Dilates skin arterioles: + Constricts skin arterioles: skin blood flow. pskin Woadiflow, Promotes sweating. Stimulates erector pili muscles Inhibits heat-promoting Shivering center. Non-shivering thermogenesis: 13/T4 release ((in long term) Inhibits heat-loss center 5. Behavioural thermoregulation: At high temperatures a. Maximize heat loss Fans (convective heat loss) Immersion in water (conductive heat loss) Staying out of sun (radiant heat prevention) Minimizing clothing b. Minimize heat production Decreased physical activity Consuming ice cream/cold water At Low environmental temperature a. Minimize heat loss Adding layer of protective clothing Curling up Standing near heat source b. Maximize heat production Increased voluntary activity Responses are mediated by cortex, basal ganglia and appropriate descending tracts. Governed by learning, memory and experience. Effect of wind on skin temperature When wind flows at high speed - warmer air touching the body is removed very fast - this causes cooling effect of air by convection. Heat acclimatisation 1. Increase in the maximum rate of sweating, 2. increase in plasma volume (due to increased aldosterone secretion) 3. and diminished loss of salt in the sweat and urine (due to increased aldosterone secretionO Applied aspects Fever Rise in body temperature above normal Release of cytokines like Interleukin-1, increase the hypothalamic set point. As the set point, increases, current body temperature compared to set- point is lower. So body initiates mechanisms for heat gain to raise body temperature to set point. That Infection/inflammation {+ Macrophages | Release Endogenous pyrogens (IL) i Antipyreti¢s__. prostaglandins (eg. aspirin) i 1 ivpothalamle set point Initiation of “cold response” | Body temperature 1 to new set point eeber is why shivering occurs and person feels chills. Chills continue till the body temperature increases to the new set-point. When the set-point comes down (may be due to removal of pathogen or by the use of antipyretics), then again the set-point comes to normal value. Then current body temperature compared to the new set-point is more. Hence body initiates heat loss mechanisms. Hence we sweat when fever comes down. Muscle pain, spasms: caused due to loss of electrolytes from body due to excessive sweating. Prevention - maintain hydration due to peripheral vasodilation and pooling of venous blood, hypotension, hypo hydration Fatigue, dizziness, weakness, thirst, profuse sweating, faintness Prevention - adequate hydration, reduce exertion on hot days, avoid standing due to negative water balance Fatigue, dizziness, weakness, thirst, profuse sweating, faintness, pale cool skin, headache, nausea, chills, unconsciousness, vomiting, diarrhoea Prevention - proper hydration before exercise, and adequate replenishment during exercise Unconsciousness, Sweating ceased, hot dry skin (due to no sweating), fast shallow heart rate, disorientation, seizures, coma Medical emergency Occurs in excessive cold environment Freezing of surface area especially in lobes of the ears and in the digits of the hands and feet. If ice crystals form in the cells, permanent damage can result. After thawing of crystals, gangrene develops, hence, frostbitten areas must be removed surgically. Used during cardiac surgery. Hypothermia reduces the metabolism of heart and of the cells. So that the body’s cells can survive 30 minutes -1 hour without blood flow during the surgical procedure Central Nervous System Higher functions Cortical function Cerebral cortex is divided into two parts Neocortex: has six layers of neurons, makes up 90% of cortex Allocortex: is formed by olfactory cortex and hippocampus. Has only three to four layers of neurons Functional Areas in cortex Cortex broadly consists of following areas: 1. Primary and secondary sensory areas 2. Motor areas - Supplementary motor area, premotor area and primary motor cortex 3. Association areas The cytoarchitecture of these areas was first described by Brodmann while functional component was described by Penfield. They are frequently referred by Brodmann numbers Primary sensory areas Primary sensory areas receive sensory information coming from opposite side of body via thalamus Primary somatosensory area: Receives general sensations. Located in parietal lobe just behind the central sulcus (Brodmann area 3,1,2) Primary visual cortex: receives visual information. Located in occipital cortex (Brodmann area 17) Primary auditory cortex: receives auditory information. Located in posterior part of superior temporal gyrus (Brodmann area 41 and 42) Primary gustatory area: Receives taste sensation information. located in anterior part of insula and frontal cortex (Brodmann area 43) Secondary sensory areas Further processing of sensory information occurs in these areas See pdf on motor cortex in motor system Primary motor cortex (Brodmann area 4): sends the commands to spinal cord for executing the motor act. Located in frontal lobe anterior to central sulcus Premotor area (Brodmann area 6) and supplementary motor area — located in frontal cortex anteriorly. For planning of the motor act 1. Parieto-occipitotemporal association area: Receives information from somatosensory area located anterior to it, visual cortex situated posterior to it and auditory cortex located laterally Due to this, it interprets the information based on all kinds of sensory information reaching the cortex Consists of: Spatial coordinates determination area - helps determine the location of a person, thing in space Wernicke’s area: For comprehension of speech Angular gyrus - most inferior part of posterior part of parietal lobe- for comprehension of read words Broca’s area: for sentence formation and word pronunciation Naming area: For Wernicke’s and Broca’s area see pdf on Physiology of speech 2, Prefrontal association area a. Plans complex patterns of movement Receives sensory input from parieto occipito temporal association areas (hence receives holistic interpretation of sensory information especially spatial coordinates). This is important for planning patterns of movement b. Carries out thought processes 3. Limbic association area: Present in anterior portions of temporal lobe, ventral portions of frontal lobe and cingulate gyrus Concerned with behaviour, emotion and motivation Located in Inferior temporal lobe (right side in right handed people) Receives information from visual cortex and from limbic system (for recognition of emotions by facial expressions). Damage to this area causes prosopagnosia = Inability to recognise faces (however autonomic responses to familiar faces are present - so subconscious recognition is occurring) Histological structure of cerebral cortex Horizontally consists of six layers of different types of neurons and connections. Layers 1 to 3 - All areas of cortex are connected with other areas of brain by afferent and efferent connections (intracortical connections). These occur in layers 1, 2 and 3. (Layer 1 = molecular layer, Layer 2 = external granular layer , layer 3 = external pyramidal layer) Layer 4 (Internal granular layer) - Layer 5 (internal pyramidal layer) - output from cortex to spinal cord Layer 6 (multiform layer) - output from cortex to thalamus Projections from nonspecific thalamic nuclei are distributed to all the layers of the cortex Only projection neurons from cortex, are excitatory and release glutamate Have cell bodies in all layers of cortex except layer 1 Pyramidal neurons in layers II and Ill project their axons to other areas of neocortex (forms subcortical association fibre bundles, connecting one part of brain to other part) Pyramidal neurons in the deeper layers V and VI project out of the cortex, e.g. to the thalamus, brainstem, and spinal cord Interneurons Inhibitory interneurons: Basket cells and Chandelier cells - release GABA Excitatory interneurons: Spiny stellate cells (example of multipolar neuron), Vertically, cortex is organised as columns. Each column of neurons has similar response characteristics - hence termed as basic repeating functional unit of cortex E.g, ocular dominance column - respond to input from one eye or other Corpus collosum The two cerebral hemispheres are connected by corpus callosum. Neurons from one cerebral hemisphere project to other hemisphere via corpus callosum. This is important for transfer of information from one to other hemisphere. Cerebral dominance vs complementary specialisation of hemispheres The area of language and speech is more developed in one cerebral hemisphere (mostly left). This hemisphere was previously known as dominant hemisphere. However, this concept is not accepted now. Now it is known as complementary specialisation of hemisphere i.e left hemisphere (95% of times) is more important for sequential analytical processes (also known as categorical hemisphere) - for Spoken and written language, Mathematical skill, Analytical ability, reasoning, scientific skills while Right hemisphere is for visuospatial relations (also known as repre: isphere) — for Visuospatial orientation, identification of objects by their form, recognition of face, image, music, art awareness, 3D awareness, imagination, insight This specialisation of hemispheres is also related to handedness In 96% of Right handed people and in 70% of left handed people - left hemisphere is categorical hemisphere Language disorders - fluent, non fluent, anomic aphasias (see pdf on physiology of speech) Agnosia: Inability to recognise objects by a sensory modality even though the sensory modality itself is intact E.g. Astereognosis - Inability to identify objects by form Hemineglect - neglecting one side of body and the visual space surrounding that side of body (lesion in parietal lobe) It also has some impact on speech - e.g. inability to tell a story, making a joke or getting point of a joke Central Nervous System Higher functions Physiology of speech We can communicate with others via three ways 1. Spoken speech 2. Written text 3. Sign language For communicating effectively, we need to 1. Perceive the words/language of others - by listening to words/ viewing what is written or what is being communicated by sign language or even by touching (for e.g. reading Braille by blind individuals) 2. Process the language - what do the words actually mean - language wise , also what is the emotional component of the language 3. Devise a response based on the communication we comprehended 4. Make a motor response - speak, write or make hand gestures Brain combines multiple inputs to generate meaningful language for conveying information. Hence many areas of brain work together for effective communication Areas of brain involved in speech- Primary speech areas: Mostly (95% people) these areas are more developed on left hemisphere of brain: Categorical hemisphere 1. Wenicke’s area (Sensory speech area): Area 22 Located posterior to auditory cortex - in posterior part of superior temporal gyrus Fundamental For understanding the meaning of the language and for devising an appropriate response, Wernicke’s area receives inputs from lot of other areas - From Auditory cortex - From visual cortex - From Angular gyrus (Located posterior to Wernickes area- in anterolateral region of occipital cortex. Function: meaning of read words fed into Wernickes area) ~ From Naming area - located laterally in most anterior aspect of occipital lobe and most posterior part of temporal lobe From prefrontal association area - Elaborated thoughts From limbic association area - Emotions attached - From parieto-occipito-temporal association area - Spatial coordinates - of the person speaking Also the existing memories - because interpretation of language depends on what is already known Based on the inputs, Wernickes area makes sense of information From Wernicke’s area, information reaches to Broca’s area via arcuate fasciculus 2. Broca’s area (Premotor speech area): Area 44 In front of the inferior end of the motor cortex Function: Forming sentence, word pronunciation, motor patterns Articulation For the motor execution of the formed sentences, we need involvement of primary motor cortex, basal ganglia and cerebellum (as is for any motor execution). This causes coordinated muscular movements of mouth, tongue, vocal cords Physiology of speech (circuitry) see (visual cortex) Elaborated Emotions thoughts attached (Prefrontal (Limbic Abgubngynis Hear association area) association area) —_ important for making (Auditory meaning of read words cortex) \, Spatial coordinate <—_— (Parieto-occipito- Wernicke's area temporal association area) Arcuate fasciculus Broca's area Primary motor cortex, basal ganglia, cerebellum Articulation - Muscles of vocal cord, jaws, lips, tongue, facial expression, limb movement & sign language Role of right cerebral hemisphere (representational hemisphere) Representational hemisphere helps us — Recognize rhythm, tone, stress, pitch (Prosody) = Conveyance of emotional state - Use of punctuation symbols when writing — In musical skills Aphasia Aphasia is loss of or defective language due to damage to the speech centres within the categorical (dominant) hemisphere. There is no damage to vision, hearing or motor paralysis. Note: defective language can occur with damage to other areas as well i Or speech articulation problems when there is paralysis of vocal cords, or facial paralysis But these speech disorders are not termed as aphasias. staccato speech - due to damage to cerebellum Types of aphasias Nonfluent aphasia - Damage to Broca’s area Fluent aphasia - Damage to Wernicke’s area (sensory aphasia) or Arcuate fasciculus (conduction aphasia) Anomic aphasia Damage to Broca’s area Understanding of the language is normal but word pronunciation and sentence formation abnormal, speech is slow E.g.: Patient with Broca’s aphasia describing his medical history: “L see...the dotor, dotor sent me...Bosson. Go to hospital. Dotor... kept me beside. Two, tee days, doctor send me home.” Sensory aphasia (Wernicke’s aphasia) Damage to Wernicke’s area Patient hears words normally but is not able to make meaning of the words/sentence Patient does not understand the language , however word formation is normal. But since word formation does not has any relation with what people are trying to communicate (since patients do not understand), patient speaks fluent meaningless words (no thought in the language) with neologism (newly coined words) Arcuate aphasia = Conduction aphasia Damage to arcuate fascicles Connection between Wernicke’s area and Broca’s area is lost Patient understands what is spoken and can pronounce and make sentence formation, But his speech has no connection with what he understands He listens to his own words, understands what he is saying wrong and again speaks something in order to correct Damage to Wernicke’s as well as Broca’s area Inability to understand speech as well as sentence formation Damage to angular gyrus Patient can understand heard words but cannot understand words which are read (visual information seen but not processed) This is known as dyslexia or word blindness Damage to auditory association areas - Auditory receptive aphasia Patient can understand read words but cannot understand spoken words This is known as dyslexia or word deafness Aphasia Comprehension | Repetition of | Naming Fluency (understanding) | Spoken Language Ask a yes/No Hippopotamus | Give the Spontaneous question function of | speech Can a dog fly? an object (Yes/No) and ask to name - E.g. name a thing for writing - Pencil, pen Preserved Impaired Impaired Decreased Impaired Impaired Impaired Preserved Preserved Impaired Impaired Preserved Central Nervous System Higher functions Learning and memory Definition Learning = Process of acquiring knowledge Memory = Process of storing knowledge which is learnt Memory involves encoding the knowledge which is acquired , storing it and retrieving it when needed . Learning Methods of learning may be either Methods of learning 1. Non-associative ; + Habituation v Associative Non-associative Sensitization (Relation of one stimulus to (ignore or react ) another) 2. Associative Classical conditioning Habituation Classical conditioning Operant conditioning Sensitization Operant conditioning Non-associative learning - Habituation and sensitization In non-associative learning, we learn whether to ignore or react to a stimulus. It does not need association between two stimuli. Habituation and sensitization are forms of non-associative learning which lead to short-term memory. Habituation - Learn to ignore a harmless stimulus Whenever a harmless stimulus is received, we first respond to a new stimulus by attending it. If the harmless or a neutral stimulus (irrelevant stimulus) is given repeatedly, eventually there is a decrease in response to the stimulus E.g. First time when we hear loud sound of crackers, we get startled, but soon we learn to ignore the stimulus Physiological significance: A neutral stimulus should not elicit unnecessary response - By learning to ignore irrelevant stimuli, person is free to attend other important stimuli and Physiological basis of learn from them. And that's why habituation habituation is actually the most Repeated harmless/irrelevant: stimulus ed | ee Calcium influx common form of learning. Decrease in response occurs due to | Neurotrarsmicer release inactivation of calcium channels in pre- J synaptic neuron (the neuron w [ers in postsynaptic neuron carrying the information about the stimulus). a iti Respon: Sensitization Response Increase in responsiveness to mild or non-noxious stimulus following noxious stimulus E.g. If a painful stimulus accidentally injures us, then for some time after the loud sound even a weak sound may elicit a response (generally lasts for much shorter time) Noxious stimulus applied to one pathway produces a change in the reflex strength in another pathway. This is because the pathway from harmful stimulus connects with the This ultimately leads to increased neurotransmitter release from presynaptic neuron of non-noxious stimulus (see flowchart) and hence increased EPSP in post-synaptic neuron causing increased frequency of action potential generation. Physiological basis of sensitization Harmful stimulus serotonln released from ‘eeliasine interneurons Non nexumer cAMP in presynaptic neuron Noxious ‘J (for harm! ) harmless stimulu: eri ess stimulus) { Te AMP Ota SE Activation of protein kinase - phosphorylation of a protein on Kr chanel Blocks K* channels {Jrection potential duration \ {fvoltage gated calcium channels open calcium influx and neurotransmitter release Points to remember: Habituation and sensitization are non-associative forms of learning. In both, changes occur only in pre-synaptic neuron. Associative learning Of two types 1. Classical conditioning 2. Operant conditioning Con joning: Learning process in which an organism's behaviour becomes dependent on the occurrence of a stimulus in its environment. In associative learning, we learn to associate one stimulus to another. This leads to formation of learned response called conditioned reflexes or operant responses Classical conditioning Classical conditioning is a way of learning by identifying predictive relationship between two different stimuli- Involves pairing of two stimuli Described by Russian scientist Pavlov. Meaning of certain terms- Unconditioned stimulus: Stimulus which already produces a strong consistent and automatic response. For e.g. giving food to an animal always produces salivation. So food is an unconditioned stimulus Unconditioned response: the response which is produced to an unconditioned stimulus. In the above example, salivation is an unconditioned response. Conditioned stimulus: Unconditioned response can be conditioned (can be learned) to occur with any other neutral stimulus which originally did not produce this response. This new stimulus which also produces that response is conditioned stimulus. Conditioned response: The unconditioned response after being conditioned is known as conditioned response. Original experiment by Pavlov In classical experiment by Pavlov, ringing of bell (Stimulus to be Conditioned) | was paired with placing meat in the mouth of a dog (Unconditioned stimulus) for some time and the response was salivation (unconditioned response) Initially the dog salivated with food but not when the bell rang without the food Then the ringing of bell was paired with giving of food consistently After several attempts, even when only the bell rang, the dog salivated (it associated bell ringing with coming of food). Hence the ringing of bell became a conditioned stimulus. Initially Unconditioned unconditioned | Neutral No response stimulus response stimulus only food ——>Pog salivated | Bell rang ——> No salivation After several Pairing ——attempts> Learned response Neutral stimulus - + Unconditioned Unconditioned| Conditioned Conditioned stimulus response | stimulus response Bell rama followed Dog salivated | Bell rang —_ Dog salivated

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