13: Spinal Cord Components - 7 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 4 coccygeal vertebra - Spinal cord is continuation of CNS caudal to medulla - Spinal cord is lined by 3 meninges - In adults, spinal cord ends at L1/L2 vertebra level, while dura extends to S2 level - Large subarachnoid space (lumbar cistern) - Lower part of spinal cord is conus medullaris - Filum terminale: (pia mater projection that pierces dura) - End of spinal cord is attached to coccygeal vertebra by filum terminale - At birth, spinal cord is at sacral level - - - - 31 pairs of spinal nerves: - Cervical (8), ,Thoracic (12), Lumbar (5), Sacral (5), Coccyx (1) - Cervical: name above the vertebra, once you hit thoracic name below. C8 emerges above T1 - Below L2, lumbosacral spinal nerves (cauda equina) occupy lumbar cistern Spinal Cord does not have anatomical segmentation, functionally segmented based on spinal nerves Spinal cord is enlarged in 2 places: - Cervical enlargement: between C4 and T1 segments, to supply upper limbs with motor and sensory - Lumbar enlargement: between L2 and S3 segments, to supply lower limbs with motor and sensory External features of the spinal cord - Ventral median fissure: to identify ventral or anterior surface) - Dorsal median sulcus Internal features of the spinal cord - White matter is outside and gray matter inside - Gray matter has dorsal horn pair, ventral horn pair, intermediate zone - Dorsal horns extend to the spinal cord surface, divide white matter into a dorsal compartment and ventrolateral compartments - Gray Matter - Cell bodies of neurons and synapses - 3 main types of neurons: motor neurons, interneurons and tract cells (whose axons form ascending tracts) - Ventral horn is motor (has projection and interneurons) and dorsal horn is sensory (has projection and interneurons) - Size and shape of ventral horn varies in different segments - Ventral horn is large at cervical and lumbosacral enlargements - why - Lateral to intermediate zone, a cell column is found in segments T1-L2 and S2-S4 (intermediolateral horn) - Intermediolateral horn contains the cell bodies of preganglionic sympathetic (T1-L2) and preganglionic parasympathetic (S2-4) neurons - White Matter White matter contains ascending and descending fiber tracts - Divided into dorsal and ventrolateral compartments - Dorsal compartment has dorsal funiculus or dorsal column - In cervical segments ,dorsal column is divided into medial gracile fasciculus (lower limb fibres) and lateral cuneate fasciculus (upper limb fibers) Ascending and descending tracts Cutaneous receptors and their function - Free nerve endings - pain, temperature - Merkel ending, Meissner’s corpuscles - touch, two-point discrimination, texture recognition - Pacinian corpuscles - vibration, Ruffini endings - pressure/stretch, Hair follicle endings - soft touch Information of muscle length and degree of muscle contraction are detected (for proprioception) by muscle spindles and golgi tendon organs - Muscle spindles: receptors deep within muscles - Responsible for identifying muscle length, degree of contraction, muscle tone - Proprioceptive information - Muscle receptors in tendons: length, degree of contraction (force exerted on tendon by muscle) - First order sensory neurons connect receptors to the spinal cord - Cell bodies in dorsal root ganglia (pseudounipolar neurons) - Ventral and dorsal rootlets, ventral and dorsal roots, dorsal root ganglion, mixed spinal nerve Pain and temperature sense are carried by small diameter fibers from free endings (either thickly myelinated, thinly myelinated, or unmyleinated) Sensory Axon Sensory Receptors Aalpha (Group 1 - thick myelination, fastest) Proprioceptors of skeletal muscles Abeta (group 2 - thick myelination, 2nd fastest) Mechanoreceptors of skin (2 point discrim) Alphadelta (group III - thinly myleination, 3rd fastest) Pain, temperature C (Group IV, unmyelinated, slowest) Temp, pain, itch - - Fibers from different sensory modalities have different paths - Sensory Fibers collateralized and contact: interneurons, - tract cells (projection neurons), motor neurons (in ventral horn) - Then, ascend/descend in dorsal column Two categories of fibres: 1. Thickly myelinated fibres carrying proprioception, two-point discrimination, and vibration (from muscle spindle/meissners corpuscles) a. Cell body in dorsal root ganglion b. Main axon ascends on dorsal ipsilateral side of spinal cord c. One synapse in whole pathway d. Synapse with ventral horn motor neuron 2. Thinly myelinated fibres carrying pain and temperature cross and ascend on the contralateral side of the spinal cord a. Axon ends in tract cells. These cross spinothalamic axons and cross the midline - - - Tendon Reflex - Sensory fibers from muscle spindles contact motor neurons to mediate tendon reflex - Tendon reflexes are monosynaptic - Biceps Reflex (C5,6 - Triceps reflex C7,8 - Knee Reflex L3,4 - Ankle reflex S1 - 1a afferent/alpha motor neuron Lower motor neurons - Neurons of ventral horn in spinal cord or in motor cranial nerve nuclei - LMN named based on muscles they supply - One neuron can synapse onto LMN and UMN - Two types of LMN - Alpha motor neurons - Innervate extrafusal muscle fibers - Responsible for generation of force by muscles (power) - Gamma motor neurons - Innervate intrafusal muscle fibers - Responsible for muscle tone How to tell: LMN vs UMN 14: Ascending Sensory Tracts 1. Dorsal Column/ Medial Lemniscus System (MLS) a. Conscious sensory system b. Carries proprioception, two-point discrimination, texture recognition, vibration c. 1st order neuron axons have cell bodies in dorsal root ganglion, enter via dorsal root (pseudounipolar neurons) i. Reflexes: Some will contact interneurons in dorsal horns, others will directly contact motor neurons ii. Main axons terminate in the ipsilateral in dorsal compartment/column of spinal cord via 1. gracile fasciculus (fibres from lower limb) or 2. cuneate fasciculus (fibres from upper limb) iii. Then, 1st order axons terminate onto 2nd order neurons in the ipsilateral Gracile/Cuneatus nuclei of the medulla iv. The 2nd order axons decussate in the medulla as Internal Arcuate fibers (IAF) v. IAF fibers form the medial lemniscus (ML) vi. ML ascends to ipsilateral VPL nucleus of thalamus vii. In thalamus, synapse onto 3rd order neurons projecting from VPL nucleus to the ipsilateral postcentral gyrus 2. Spinothalamic system (STS) a. Conscious sensory system b. Carries pain, temperature, pressure, and touch c. 1st order neuron axons enter dorsal horn via dorsal root, cell bodies in the dorsal root ganglion(thinly or unmyelinated axons) i. Reflexes: Some will contact interneurons in dorsal horns, others will directly contact motor neurons ii. Main axon synapses onto 2nd order neurons (tract cells/projection neurons in dorsal horn) iii. Some of these 2nd order neurons cross over to contralateral side at SAME spinal segmental level, below central canal iv. 2nd order neurons ascend contralaterally and travel to the thalamus v. 2nd order neurons synapse onto 3rd order neurons in the VPL nucleus of the thalamus, projects to the postcentral gyrus (review homunculus) 3. Spinocerebellar system a. Unconscious sensory system b. Pathologies: Motor signs/symptoms but problem in sensory tract (ataxia) c. Carry unconscious proprioception d. Projection/tract cells e. Ventral Spinocerebellar tract is crossed i. Fibers traverse superior cerebellar peduncle ii. Cross again iii. Ends in ipsilateral cerebellum iv. Fibers decussate twice f. Dorsal (Posterior)) spinocerebellar tract is uncrossed i. Fibers traverse ipsilateral inferior cerebellar peduncle ii. Ends in ipsilateral cerebellum iii. Fibers do not decussate at all Trigeminal system: general sensation from head and neck - Trigeminal nerve (CNV) =mixed, large sensory component and small motor component. Emerges from pons - Receives all modalities of sensation (pain, temp, proprioception, 2 point discrimination, vibration, touch) from face, scalp, sinuses, oral and nasal cavities, dura mater - 3 divisions: - Ophthalmic Nerve - Maxillary Nerve - Mandibular nerve - Motor fibres here supply mastication muscles Trigeminal Nuclei - Sensory: - Mesencephalic Nuc (proprioception) - midbrain - Main Sensory Nuc (touch) - pons - Spinal Trigeminal Nuc (pain, temp) - pons, medulla, cervical spinal cord - Motor: - Motor Nuc of CNV - pons - Cell bodies of 1st order neurons EXCEPT those going to mesencephalic nucleus are in the trigeminal ganglia in cranial cavity - Cell bodies of fibers coming to mesencephalic nucleus are found within pons and midbrain, these are the only 1st order sensory neurons to have cell bodies within the CNS - Cell bodies of 2nd order neurons are in main and spinal nucleus of V - Their axons cross the midline and run adjacent to the ML as the trigeminal lemniscus to VPM nucleus of the thalamus - 3rd order neurons go from thalamus to post central gyrus 15: Descending Tracts - - Case - Left leg weakness - Decreased pain and temp on right lower limb - Decreased vibration and proprioception on left knee and ankle - Decreased muscles on left lower limb - Brisk (increased) tendon reflexes on left knee and ankle - Diagnose: injury to one-half of upper lumbar spinal cord Lower Motor neurons (LMN) - Innervate skeletal muscles - Are in ventral horns of spinal cord and in cranial motor nerve nuclei - Two types - Alpha and gamma motor neurons - Supply alpha: extrafusal (contraction/power) and gamma: intrafusal (tone) fibers - 3 sources of afferents to LMN 1. Sensory input from muscle spindles - excitatory effect 2. From spinal cord interneurons - mainly inhibitory effect 3. Inputs from any other CNS neurons that are rostral to LMN (spinal cord, brainstem or cerebral cortex): called Upper motor neurons (UMNs) - almost always contact LMNs via inhibitory interneurons, therefore exert inhibitory effect on LMNs - Effect of lesions of UMN on excitability of LMN - Increased excitability - Direct input from muscle spindles to alpha motor neurons form stretch (tendon) reflex - UMN lesion: excitability of LMNs increase, causing muscles to be spastic - Also, increased LMN excitability - stretching tendon stimulates LMNs with increased excitability = brisk reflexes - Motor Unit: an alpha motor neuron and all muscle fibers it innervates are called a motor unit - Large motor units: one alpha motor neuron innervates large number of muscle fibers control is less precise Small motor units: one alpha motor neuron innervates a small number of muscle fibers control is more precise - Ex. Lumbrical (for finger movements) - UMN - Ex. corticospinal tract (pyramidal tract) - Primary motor cortex to ventral horn of spinal cord - Cell bodies in primary motor cortex - axons pass through ipsilateral internal capsule, basis pedunculi, pons and medulla (pyramid) - Travels contralateral in spinal cord - Motor Homunculus: - - In PMC - Leg area supplied by ACA - Hand and face supplied by MCA Internal Capsule: projection fiber system - - Green = approximate location of corticospinal fibers (in posterior limb) At lower medulla, in pyramidal decussation, 85% of fibers cross over to the contralateral side to form lateral corticospinal tract Terminate in LMNs via inhibitory interneurons Signs of UM and LM neuron lesions UMN lesion LMN lesion Weakness Increased muscle tone Brisk tendon reflexes Babinski sign (inverted plantar reflex) Spastic paralysis Involuntary muscle twitching (fasciculations) Flaccid paralysis Decreased muscle tone decreased/absent tendon reflexes - - Corticobulbar tract - From PMC to motor cranial nerve nuclei - Movement of face and head - Cell bodies in precentral gyrus, axons descend through ipsilateral internal capsule (mainly genu area), traverse the basis pedunculi, pons or medulla - Cross midline and supply LMN (cross approx level of LMN) - UMN lesions produce effects on contralateral side - Exception is facial nucleus CN XII nucleus: LMNs of CNXII get UMN inputs from contralateral PMC (green) via inhibitory interneurons (like in ventral horns) - UMN lesions - effects seen in contralateral side of tongue - Facial Nucleus: LMN of CNVII supplying all muscles receive UMN inputs form contralateral PMC (green) - LMNs supplying muscles of upper face receive additional inputs from UMNs of ipsilateral PMC (purple) - UMN lesions - effects only seen in lower part of contralateral face 16: Higher Functions and Limbic System Limbic System - Involved in emotional behaviour, stress response, learning and memory - Areas include: - Cingulate gyrus: continuous on basal surface connecting to parahippocampal gyrus, then to entorhinal cortex (EC) - Parahippocampal gyrus - Hippocampus - Amygdala: underneath the uncus - Uncus: smooth area involved in olfaction - Parts of thalamus - Hypothalamus - paraventricular nucleus - Brainstem - others Hippocampus and functions - Deep structure in medial temporal lobe, deep to parahippocampal gyrus About 5cm in length If you pull medial temporal lobe away, entorhinal cortex continues deep and you see serrated dentate gyrus Temporal horn of lateral ventricle on top of hippocampus Hippocampus forms flow of temporal horn of lateral ventricle Pathology: shrinkage Hippocampal formation - Dentate gyrus (DG) - Hippocampus (CA1, CA2, CA3) - Subiculum - transition from 5 to 3 layers - No obvious external separation - Entorhinal cortex - Has 5 layers - Hippocampus has 3 layers - - - Main intrinsic circuit of hippocampus - Information goes from upper layers of entorhinal cortex and processed information returns to lower layer of entorhinal cortex Perforant Pathway (cortical pyramidal neurons) - Projection neurons in layers ⅔ send axons to dentate gyrus - DG is 3 layer cortex, axons project to CA3 via mossy fibers - CA3 (pyramidal neurons) send axons through white matter of hippocampus to CA1/2 via schaffer collaterals - Synapses between CA3 with CA1/2 important for long term potentiation - LTP first collateralized in CA1/3 synapses - declarative memory formed here - CA1 to subiculum - Pyramidal neurons in subiculum send axons to lower layers - Forms loop from upper to lower layers 1. Perforant pathway from superficial layers of entorhinal cortex 2. Mossy fibers 3. Schaffer collaterals 4. CA1 collaterals to deep layers of entorhinal cortex via subiculum Axon collaterals from CA1,2 and CA3 pyramidal neurons and axons of subicular neurons (entorhinal) form the Alveus Alveus is equivalent to subcortical white matter of cerebral cortex (outside gray matter) White matter becomes fimbria Hippocampus often called inside out cortex bc gray matter inside, white matter outside Fornix - Alveus becomes fimbria and then fimbria becomes fornix - Fornix is white matter fibre bundle carrying afferent and efferent fibers of hippocampus to anterior structures. Have L/R fornix - Goes anterior toward mamillary bodies and connects with thalamus - Alzheimers: degeneration of basal forebrain. These fibres pass through fornix to reach hippocampus Papez circuit: involved in emotion and memory - Cingulate cortex projects to entorhinal cortex, then to hippocampus - Information processed in hippocampal formation, sent through fornix to hypothalamus - Then to anterior nucleus of thalamus - Cingulate cortex receives information from all cortical areas (all areas project to cingulate cortex) Hippocampus involved in: - Formation and consolidation of declarative memory - *not stored - Spatial orientation, spatial navigation and spatial memory - Pattern completion and recognition - Cognitive/behavioural flexibility - Emotional responses - Stress responses - identify if stressors are important stressors If there is global ischemia: first part of brain to die is hippocampus - very sensitive - Supplied by PCA Amygdala and functions - R/L amygdala have different functions in humans - Involved in - Autonomic and endocrine responses to fear - Endocrine response: HPA axis, autonomic - SNS - PVN of thalamus → brainstem autonomic areas - Fear conditioning and fear memory - Emotional value of events/facts - Emotional memory and response - Arousal - Aggression - Sexual orientation - Social interaction Reticular formation functions - Interconnected diffuse groups of nuclei (collections of neuronal cell bodies) crisscrossed by fiber tract (white matter) and distributed throughout brainstem (midbrain, pons, and medulla) and parts of the hypothalamus - Brainstem reticular formation sends axons to cerebral cortex, thalamus and hypothalamus, and these pathways are collectively called ascending reticular activating system (ARAS) - ARAS responsible for wakefulness and consciousness - Brainstem reticular formation also sends axons to spinal cord and this forms reticulospinal tract (controls posture, and axial muscles) - Contains ascending and descending neuromodulatory pathways Modulatory systems controlling neurotransmission Modulator Cell body Target areas functions Dopamine Midbrain Basal ganglia, cerebral cortex, amygdala Basal ganglia function (motor), limbic function, reward, learning and memory Serotonin Midbrain and pons All areas of CNS Mood, sleep, appetite, sexual desire, reward, learning and memory Noradrenaline medulla All areas of CNS Wakefulness, attention, stress response, mood, sleep, learning and memory Acetylcholine Midbrain and pons All areas of CNS Attention, alertness, habituation, emotion, sleep, learning and memory Histamine Hypothal amus Forebrain areas Arousal, energy balance, learning, memory, sleep Primary and association cortical areas and their functions - Most areas of cerebral cortex are association cortex - Primary cortices(red): primary motor cortex, primary somatosensory cortex, primary visual cortex, primary auditory cortex - Multimodal association cortex (green) - Unimodal association cortex (yellow) Higher order brain functions Eg. motor planning, language processing and production, detail sensory perception, determining socialy appropriate behaviour, executive function Multi-modal association cortices mediate higher-order functions through multiple interconnected circuits 17: Autonomic Nervous System and Homeostasis Compare ANS to somatic NS Viscera = organs: heart, stomach, intestines, organs Autonomic: smooth muscle, cardiac muscle, lacrimal gland - not voluntary Describe pathways of sympathetic output from spinal cord to effector organs in body periphery, head, and visceral organs - Basic Pathway - CNS has preganglionic neuron cell body - PNS has preganglionic axon, postganglionic neuron synapses onto target - Ganglion - CNS has many preganglionic neuron cell bodies - PNS has collection of pre gang -postganglionic synapse - creates ganglion - Ganglion synapse: acetylcholine - Target synapse: Ach (PSNS) and Norepi (some Ach) (SNS) Autonomic origins in CNS - Parasympathetic = craniosacral origin [brain stem + spinal segments (S2-S4)] - Sympathetic = thoracolumbar origin [spinal segments T1-L2] - motor horn Effect of SNS innervation on each effector organ Post sympathetic ganglia form sympathetic chain/trunk close to spinal cord Ganglia at each level Paravertebral trunk/plexus = behind Prevertebral plexus = in front of aorta. Goes to abdominal and pelvic viscera Extends from neck to coccyx Post ganglionic fibres innervate glands, smooth muscle, blood vessels SNS innervates thoracic, abdominal, and pelvic viscera 1. Peripheral Target at level of origin (above) a. T1-L2 with lateral horn with nerve cell bodies b. Leave via anterior root and form spinal nerve c. SNS fibers leave the spinal nerve via whtie rami communicantes. d. Can synapse here and leave via gray rami communicans e. Rami communicans: white = going in, myelinated. Gray= non myelinated, slower, leaves ganglion 2. Target at different level from origin (above right) a. White rami communicantes leave lateral horn b. Fibers pass through up or down chain, Synapse at level they wish to innervate (C2-C8, T1-L2, L3-Coccyx) c. Leave via grey rami communicantes d. Fibers synapse, post ganglionic fibers can ascend/descend and exit at higher level e. Sympathetic innervation in the head i. Sympathetics passing into the head have preganglionic fibres emerging from the spinal cord at T1 ii. These fibres synapse in superior cervical ganglion (3 cervical ganglia - superior, middle, inferior) iii. Fibres (GRC) continue to travel along blood vessels (internal carotid artery) to target structures - form plexus around the ICA iv. Innervation of thoracic and cervical viscera (levels T1-T5) v. No WRC above T1 vi. Abdominal viscera below T5 3. Visceral target in abdominopelvic cavity a. Alternative seen in cardiac nerves and abdominopelvic cavity b. T5-L2 i. Pass through ganglia without synapsing, preganglionic fibres assess into abdominopelvic cavity and synapse at prevertebral ganglia (aorta in front of vertebra) ii. These are splanchnic nerves c. Do not leave via gray rami d. Synapse with postganglionic cell body and form plexus near aorta e. Adrenal Medulla i. Passes through without synapsing ii. Release noradrenaline to stimulate SNS Pathway of parasympathetic output through cranial nerves and sacral spinal nerves to visceral organs - PSNS is all ACh 3 CN have PSNS fibres - Innervate submandibular, sublingual, lacrimal glands, structures in eyes (dilator, ciliary muscle for lens) - Vagus nerve goes to heart/lungs/small intestine/2/3 l intestine - Distal lg intestine and pelvic organs innervated by sacral origins of PSNS fibers Describe effects of PNS innervation on each visceral organ innervated by this division Combined Systems - Sympathetic T1-L2 - Forms paravertebral trun - Some fibres synapse in preverterbral ganglia surrounding abdominal aorta - Form hypogastric nerve - Parasympathetic S2-S4 and cranial nerves III, VII, IX, X - Join sympathetic fibres at inferior hypogastric plexus Head and Neck autonomic nerves - PSNS - synapse close to target origin, small ganglia - CNIII: Ciliary ganglion → pupillary constriction - Posterior to eye - CNVII: Pterygopalatine ganglion → lacrimal gland - Submandibular ganglion → salivary glands - CNIX: Otic Ganglion → parotid gland - Anterior to foramen ovale - CNX doesnt innervate head/neck - SNS - pregang ascends, either join spinal nerves surrounding superior ganglion for neck sweat glands or GRC join it onto ICA and travels to head Explain concept of referred pain - Visceral sensory neurons: - General visceral receptors monitor stretch, temperature, chemical changes, and irritation within visceral organs - Brain interprets info as feelings of hunger, fullness, pain and nausea - Visceral sensations are difficult to localize precisely - Cell bodies of visceral organs are located in dorsal root ganglia and in sensory ganglia of cranial nerves - Some visceral afferent fibres accompany PSNS nerves (Vagus), others travel with SNS nerves to autonomic plexuses, splanchnic nerves, sympathetic trunk to rami communicantes to spinal nerves and dorsal root ganglia - Most visceral pain fibres follow SNS route - Visceral pain is hard to localize - general. Nerves travel a while to get to target, might feel pain elsewhere - Referred pain - Pain resulting from an organ which radiates to the dermatome level which received the visceral afferents for the organ involved - Ex. Stomach - supplied by greater splanchnic originating from T7/T8 - Cardiac referred pain - Spinal cord segments for cutaneous nerves of upper limb (T1-3) also common to cardiac visceral afferents - Communication at spinal cord level through connector neurons can refer pain to right side as well 18: Olfaction and Taste Structure and Function of nasal cavity and tongue in relation to olfaction and taste - Olfaction - Odour particles swirl around and get caught in the nasal mucosa in the nostril - Gets caught in most superior aspect - caught in olfactory epithelium and now you can smell - Picture: blue = cribriform plate (very thin bone) purple= nasal cavity. Olfactory bulb at superior aspect of cribriform plate (ethmoid bone), olfactory tract passes backwards. Below nasal cavity = palate (separates nasal/oral cavity), houses the tongue - Olfactory Epithelium: Olfactory Mucus at bottom: traps odour particles in epithelium. Mucus is produced by bowman's/olfactory gland (in lamina propria) Lamina Propria: above olfactory epithelium, connective tissue layer, houses Bowman’s gland Olfactory Sensory Neurons: responsible for sense of smell, bipolar neurons, body in epithelium, processes sent below have cilia (for tasting odourant particles) and processes sent above through cribiform plate. These axons travel together and form the filaments of olfactory nerve and travel through the cribriform plate Glomeruli: synapse between olfactory sensory neurons and mitral cells in the olfactory bulb Mitral cell = output cell of olfactory tract. Axons form the olfactory tract, goes towards cerebrum Supporting cells = in epithelium, support sensory neurons, secrete odourant binding protein (secreted into mucus, traps odourant particles) Olfactory Stem cell: in epithelium, helps with regenerative property of olfactory epithelium, can differentiate into any of the cells in the epithelium Olfactory Bulb (left): has glomeruli, synapse between olfactory sensory neurons and mitral cells. Cell bodies of mitral cells make up this tract. Connect olfactory bulb to Olfactory Tract (middle): Axons of mitral cells travelling from olfactory bulb towards cerebrum Olfactory Neural Pathway - Goes to lots of different places in cerebrum (midbrain, hypothalamus, etc) Travels to: - Primary olfactory cortex (piriform and periamygdaloid cortex, entorhinal cortex, perirhinal cortex) all in temporal lobe area (as well as uncus) - Contralateral (via anterior commissure) and ipsilateral aspect - **Only sensory innervation that does not go through the thalamus before going to the cortex gated - Olfactory Bulb (inf. Frontal lobe) → olfactory tract → NOT gated through thalamus. - Hippocampus (Limbic): olfactory memory - Amygdala (Limbic): motivational and emotional responses to smell - Hypothalamus: motivational and emotional responses to smell Reticular Formation: Autonomic response to smell, starts gastric secretions Midbrain: Diagram incorrect: no fibres go directly to thalamus from the olfactory tract. Goes other places and then goes to thalamus - Fibres only get to thalamus after the olfactory cortex. Goes to Medial Dorsal nucleus → orbitofrontal cortex for conscious perception of smell Olfactory projection Pathways Taste - Various triggers initiate saliva secretion - Via salivary glands under PSNS control - Parotid, submandibular, sublingual, - Mastication helps break down food into smaller pieces to be able to swallow it - Interplay of multiple cranial nerves to chew, sense, taste, swallow - Particles go into taste buds to taste, then go down esophagus - - Anatomy of the tongue - Superior/Dorsal view - Body of tongue (anterior), Root (posterior) - Terminal Sulcus: line demarcating difference between anterior ⅔ and posterior ⅓ of tongue - Circular structures: circumvallie papillae: allow us to taste - Epiglottis: posterior, Motor Innervation (entire tongue): - Tongue Movement: Hypoglossal Nerve CNXII - - - Both intrinsic and extrinsic tongue muscles CNXII travels through hypoglossal canal, on lateral side of foramen magnum. SPinal cord and vertebral arteries pass through foramen magnum - Originates off of medulla General Sensory Innervation - Sense Food texture - Anterior 2/3rd: Trigeminal Nerve (mandibular division, lingual nerve) Mandibular division of CNV passes through foramen ovale (third black line) - Posterior 1/3rd: Glossopharyngeal Nerve CNIX passes through jugular foramen. PSNS innervation to parotid gland. (PSNS and sensory inn) - Taste: Special Sensory Innervation - Epiglottis: Vagus Nerve - Not part of tongue, covers trachea to make sure food doesnt go into lungs - PSNS to thoracic and abdominal viscera, also taste to epiglottis Travels through jugular foramen (from medulla) “Wandering Nerve” Posterior 1/3rd: Glossopharyngeal N Anterior 2/3rd: Facial Nerve (Chorda Tympani N) - Facial nerve passes through the acoustic meatus Provides PSNS to sublingual and submandibular gland SUMMARY Anterior 2/3 Posterior 1/3 Epiglottis General Sensory Trigeminal (Lingual N) Glossopharyngeal Vagus? Taste Facial (Chorda TYmpani N) Glossopharyngeal Vagus Motor Hypoglossal Hypoglossal Location, function, and morphology of olfactory receptor cells and taste buds on histological and gross anatomical images - Olfactory Epithelium = pseudostratified columnar epithelium with cilia. Have nuclei in this area. - Lamina Propria= connective tissue layer with bowman’s gland and filaments of the olfactory nerve (big circles) Cilia of olfactory receptor 4: Cribriform plate Gustation - Taste occurs via papilla, 4 types - Foliate papillae (lateral), Circumvallate (large posterior), Fungiform (anterior dots), Filiform (smaller) - Filiform does not have taste buds, for mechanical breakdown 5 types of taste receptors 1. Salty 2. Sweet 3. Sour 4. Bitter 5. Umami Histological: (tongue is stratified squamous epithelium) - - Filiform: “Flames”, used for mechanical breakdown Circumvallate: dots on side = taste buds Fungiform: mushrooms Foliate: lateral, folds Taste Bud: - Gustatory Hair Cell: specialized epithelial cell, has taste receptor, activata nd send impulse via CN, finger like projections - Taste Pore: area of epithelium allowing for food particles to get into taste bud and sensed - Gustatory EPithelial Cells: similar to supporting cells in olfactory epithelium, amek up rest of epithelium - Basal cells: like olfactory SC, help regenerate gustatory cells Differences: - Olfac: supporting cells w sensory neurons poking through (sensory neurons not epithelial cells - Gustatory hair cells are actually epithelial cells, just specialized - Nerve pathways of olfaction and taste, starting in the face and terminating in the brain Olfactory nerve (CNI) - Sensory neurons travel through plate and into olfactory bulb (ventral cerebrum) - Responsible for smell and 80% of taste (special visceral sensory) - Origin: olfactory receptor cells (bipolar neurons) in olfactory epithelium of the nasal cavity - Nerve Pathway: pass through cribriform foramina of ethmoid bone to synapse in olfactory bulb - Fibers of olfactory bulb neurons extend posteriorly beneath frontal lobe into olfactory tract - Terminate in primary olfactory cortex of cerebrum Gustatory Neural Pathway - Via CN to solitary nucleus of the medulla - Then to ventral posteromedial nucleus in thalamus (gets gated) - Goes to ipsilateral insular lobe (gustatory cortex) Clinical Scenarios Olfaction 1. A 27 year old man was recently involved in a car accident that resulted in him getting rushed to the emergency department with severe facial trauma. Thankfully, he was stabilized and brought for several scans to investigate whether he had sustained any brain damage. Upon scanning, the radiologist discovered that he had fractured his ethmoid bone, but also noticed that he had clear fluid leaking from his nose. a. This is CSF leaking out. Meningeal coverings over the brain, closely related to ethmoid bone and olfactory bulb. Shred through ethmoid bone → shred through meningeal covering. Direct pathway for CSF to leak out 2. A few weeks after the accident, the man has recovered substantially, however, complains of an inability to smell with some loss of taste abilities. He goes to the doctor and is diagnosed with anosmia. a. Potential Cause for anosmia (inability to smell): olfactory sensory neurons travels through the cribriform plate, these get damaged if bone is cracked → slice through neurons, inability to smell (pick up odourant particles and allow us to smell) b. Why some loss of taste abilities: 80% of taste is smell. If you damage olfactory sensory neurons, you damage sense of taste as well. i. Other than 80% Gustation 1. A woman visits her doctor because she has recently been having issues moving the right side of her tongue. When asked to stick her tongue out, it deviates to the right side. She insists she feels fine, but as a precaution, her doctor sends her to the hospital for scanning. Cause of tongue paralysis? a. Right side Hypoglossal Nerve damage 2. Upon arrival at the hospital, the woman is brought in for scanning and results show an aneurysm (enlargement) of her right vertebral artery as it passes through foramen magnum to get to the cranial cavity. Using your past knowledge of the cranial foramina and their locations, how might this aneurysm be playing a role in her tongue paralysis? a. Hypoglossal Nerve passes through the hypoglossal canal, close to foramen magnum. Large aneurysm will press on this 19: Visual System - The eye has 2 chambers - Retina = similar to grey matter - Optic nerve = white matter features - not a peripheral nerve - Images get inverted Pathways conveying visual information to the cerebral cortex and associated reflex pathways - Retina - Cones= Colour detector, in bright light. Macula also colour vision - Rods= dim light, peripheral vision - Pathway of light through the retina: - Passes through: - Ganglion cells - Interplexiform cell - Amacrine Cell - Bipolar Cell - Horizontal cell - Rods/Cones - Light is absorbed by choroid at the back And then makes its way back to the ganglion cells - Axons of ganglion cells exit via optic papilla and form optic nerve - - - Optic Nerve: collection of ganglion cell axons. Enclosed in dura with CS. therefore increased CSF pressure affects the retina by obstructing venous return → engorged veins → Papilledema (seen with ophthalmoscope) - Papilledema: vision is usually normal Optic Papilla/Disk: slightly medial, pale, about 1.5mm in DM. blind spot Macula: about 5mm in DM, yellow under red-free light, no large blood vessels Fovea: 1.5mm in DM, appear darker than the surrounding macula. Only cones in fovea. So depth perception(?) and colour - 80% of optic nerve fibres come from macula Optic nerve fibers from nasal halves (seeing lateral) of the retina cross to other side of optic chiam. Temporal halves (seeing medial) = ipsilateral. Optic nerve, then cross at optic chiasm .Now tract - Info from each visual field is received by both eyes - Retinal Projections are topographically organized This pic is left visual field? Retinal Axons Projection 1. To LGN of Thalamus → PVC (conscious vision) a. Right LGN and Right PVC receive info from left visual field (NOT EYE) b. PVC = upper and lower calcarine sulcus 2. Superior Colliculus (Eye movements) 3. Pretectal Area (Pupillary Eye reflex 4. Hypothalamus (Circadian rhythm) a. Preoptic and Suprachiasmatic nuclei b. Reset circadian rhythm Visual Field Defects - Lesion in right optic nerve → blind in right eye - Lesion in optic chaism midline → bitemporal hemianopia (no periphery) - Lesion in right edge of chiasm → nasal hemianopia, right eye - Lesion in Right optic tract → loss of left hemi visual field Eye movements, extraocular muscles, and their innervation Sphincter pupillae: PSNS, muscle contracts to constrict pupil Dilator pupillae: SNS, muscle contracts to dilate pupil Pupillary Light Reflex Bright light → retina → pretectal area (bilateral projection, contralateral via posterior commisure, responsible for consensual light reflex (opposite eye constricts too) → Edinger-Westphal Nucleus → via oculomotor nerve to Ciliary ganglion → ciliary muscles → pupillary constriction Reflex, does not go to thalamus. Just the midbrain. Edinger - Westphal nucleus in front of cerebral aqueduct Corneal Reflex Touch cornea → Afferent: Nasociliary branch of V1(trigem) → direct connection to facial nucleus (in pons, bilateral connection for some consensual reflex) → Efferent: Zygomatic branch of Facial nerve → Orbicularis oculi muscles → Blink When you touch cornea, constrict orbicularis oculi and blink Eye Movements 3 Targetting movements: 1. Saccades: rapid acquisition of new target 2. Smooth pursuit: follow moving target 3. Vergence: direct fovea at targets of far/close 2 Compensatory reflex movements 1. Vestibulo-ocular reflex (VOR - compensates for acceleration) 2. Optokinetic movements - compensates for fixed-velocity movements - Both VOR and optokinetic movements depend on vestibular input Extraocular Muscles Muscle Action Cranial Nerve Lateral Rectus Move eye laterally VI: Abducens Medial Rectus Move eye medially III: Oculomotor Superior Rectus Elevate eye and turn it medially III: Oculomotor Inferior rectus depress eye and turn it medially III: Oculomotor Inferior Oblique Elevate eye and turn it laterally III: Oculomotor Superior Oblique Depresses eye and turns it laterally IV: Trochlear Cranial Nerves III, IV, VI pass in cavernous sinus, then through superior orbital fissure to enter the orbit 20: Auditory System Temporal Bone - Bony external auditory canal - Internal Auditory Meatus on petrous temporal bone in posterior cranial fossa - CNVIII (vestibulococh), CNVII (facial), Nervus intermedius nerve - taste fibres from tongue - pass through internal auditory meatus (foramina) - Leberenden artery and vein pass through internal auditory meatus as well - Tentorium cerebelli reflected off of petrous temporal bone (roof of middle cranial fossa) Sound Conduction - Housed in temporal bone - Otoscope: can see tympanic membrane - Ossicles in middle ear transmit vibrations in air to cochlea (inner ear) - Ossicles attached to each other, stapes is attached to oval window - Stylomastoid foramina - Vibrations in air hit tympanic membrane, transmitted through ossicles, reach oval window, vibration pass through fluid filled cochlea, detected by hair cells Sound - Intensity of sound is measured in dB - Normal human speech is about 60dB, while >120dB may cause pain and hearing loss (jet engine is about 150dB) - Can identify presence of sound and intensity fo sound - Time difference and intensity difference between sound received by each ear (cochlea) helps to identify the location of the sound - Sound waves/vibrations reach tympanic membrane (separates external and middle ear), then carried by movements of chain of ossicles to oval window of cochlea - Movements/stiffness of muscles controlled by 2 muscles innervated by CNV and CNVII - - Bony structure with membranous structure and fluid filled compartments Inner ear has vestibular and cochlear (auditory) organs Cochlea coils for about 2 ½ turns and apex is called modiolus Cross section of cochlea: - 3 cavities: - scala vestibuli, - filled with perilymph (top half of photo change name) - scala media, - filled with endolymph (cochlear duct) - Contains sensory receptors (organ of Corti) - scala tympani - filled with perilymph - Cochlear nerve - Bony labyrinth = cochlear canal - Membranous labyrinth = cochlear duct - Perilymph is similar to CSF (low K and high NA) and endolymph is like cytoplasm (high K and low Na) - - Uncoil the cochlea: - Sound is transmitted from stapes to scala vestibuli via oval window → information produces pressure waves in perilymph, then transmitted to endolymph of scala media - Pressure waves produced in endolymph stimulates receptors of scala media - Vibration is returned through scala tympani via round window - round window dampens the vibrations - Organ of Corti - sensory receptors in scala media - Hair cells - Supporting cells - Tectorial membrane - Pressure waves moves the basilar membrane, this movement bends hairs of inner and outer hair cells → this information then carried by cochlear nerve fibers (VIII cranial N) - Basilar membrane is thicker, gets thicker as you go on tectorial membrane lines bony labyrinth. Tectorial membrane reflected onto haircell. Gelatinous membrane - hairs inserted into tectorial membrane. Stereocilia = hair. Endolymph vibrates basilar membrane causing hair to bend (stimuli) - Bending causes opening of K+ channels - elec signal Cell bodies of 1st order cochlear neurons are found in spiral ganglion (in cochlea) whose axons form the cochlear division of cranial nerve VIII) Auditory Pathway - CN VIII → dorsal and ventral cochlear N → superior olivary N → inf colliculus → MGN (medial geniculate nucleus) in thalamus → primary auditory cortex - Several points of decussation occur along above pathway - Auditory cortex receives info from ipsilateral ear and contralateral ear (helps for binaural processing of auditory stimuli - Tonotopic organization of auditory pathway - Tonotopy is maintained from cochlea to primary auditory airway Vestibular System - - - - - Case study: - Woman has vertigo (sense of room spinning), nausea - Worse symtpoms when she looks up - Nystagmus - Diagnosis: Benign paroxysmal positional vertigo - Treat with Epley meneuver (moving head in certain directions, then still head) Vertigo: sensation in which an individual or objects around them is/are spinning/swaying while they are not - Often associated with nystagmus and nausea Nystagmus: dancing eye, an involuntary eye movement and may be manifested by asymmetrical stimulation of right and left vestibular apparatus - Eyes move slowly and then back fast - Direction of fast phase is considered the direction of nystagmus Inner ear contains vestibular apparatus and cochlea Vestibular apparatus consists of a membranous labyrinth with endolymph Receptors are submerged in endolymph Vestibular apparatus: saccule, utricle, and 3 semicircular ducts (anterior, posterior, and horizontal) - Saccule and utricle detect: linear acceleration and deceleration and gravity (aka static labyrinth) - receptors are macula utriculi and macula sacculi respectively - - - Semicircular ducts detects rotation of head (aka kinetic labyrinth) - receptors are crista ampullaris in ampulla of each semicircular ducts Static labyrinth: utricle and saccule - Sensory areas: - macula utriculi (30 deg above the nasooccipital plane - base of skull) - Macula sacculi (vertical to skull base) Tips of kinocilium and stereocilia are embedded in a gelatinous cap (otolithic membrane) - Contains Ca carbonate/protein crystals (otoliths) and whole complex is submerged in endolymph \ - - Otolithic membrane has a higher specific gravity than the surrounding endolymph (because of otolith - change in head position or gravity cause movement of otolithic membrane and this stimulates hair cells Kinetic Labyrinth: semicircular ducts - Anterior and posterior ducts are in vertical plane (90deg to each other) and horozontal (latral) duct is 30deg to naso-occipital plane (skull base) - Tips of the kinocilium and stereocilia are embedded in a gelatinous cap called cupula that lacks otoliths, whole complex is submerged in endolymph - Cupula has same specific gravity as surrounding endolymph, therefore not affected by gravity - Movement of endolymph bends the cupola - - - - Direction of bending cause depolarization or hyperpolarization of nerves Vestibular nuclei - Medial - Lateral - Superior - Inferior - Medial longitudinal fasciculus connects CNIII, IV, and VI nuclei and medial vestibular nucleus, and cervical spinal cord bilaterally - Medial longitudinal fasciculus coordinates eye movements with head and neck movements - Descending vestibulospinal tract (from lateral vestibular nucleus) controls axial and proximal muscles to coordinate balance and posture Vestibulo-ocular reflex (VOR) - Responsible for compensatory eye movement to opposite side in response to head rotation Benign paroxysmal positional vertigo = when piece of otolith is dislodged from otolithic membrane of utricle and gets into semicircular duct Epley maneuver removes piece of otolith from semicircular duct and moves it back to the utricle Neurological Disorders of CNS’ Stroke - Stroke: brain cell death due to lack of oxygen and glucose due to vessel blockage or rupture - Second most common cause of mortality world-wide (WHO) - Lie-time risk ~25% - Acute onset of neurologic deficits - Hemiparesis or hemisensory loss - Gait or limb ataxia - Aphasia - Visual Neglect - visual input decoded, difficulty attending to a side. Walk into things, usually neglect to left side (right side lesion in parietal cortex (or frontal/thalamic) - Ocular motor abnormality - Two types of stroke - Ischemic - Caused by blood clot blocking vessel in brain (80% of stroke) - Also caused by artery narrowing - stenosis due to atherosclerosis - Treatment: clot-busting drugs, interventions with catheters - Interventions for ischemic stroke - First line: Clot-busting drugs tpa - if within a few hours of onset, after that risks outweigh benefits - Routinely send them for angiogram and thrombectomy - Catheter aspiration thrombectomy: syringe suction to aspirate debris - Mechanical Thrombectomy: saline jets or rotating catheter head breaks up thrombosis before its aspiration - Hemorrhagic - Blood vessel breaks and bleeds into brain - Treatment: - Finding cause of bleeding and controlling it (sometimes with surgery) - Control high blood pressure if present (beta blocker) - Confirm clotting factors and platelets normal (infuse platelets and enhance clotting factors with vitamin K or infusions) - Interventions for aneurysms/hemorrhagic stroke - Clip aneurysm to isolate it from normal circulation - Coil embolization: fills aneurysm with material that closes off the sac - Transient ischemic attack (TIA): a mini stroke - where blood supply to brain is blocked for a short time (symptoms last <24h). Damage is not permanent but is associated with increased risk of having a stroke - Angiography: insert catheter into femoral artery, steer it into areas of concern. Insert dye in relevant region. Aneurysm- ballooning of arterial wall - weakened - can rupture Category subtypes Ischemic subtypes - if blockage is closer to heart, larger area of cortex relying there more diffuse damage. Peripheral blockage causes less damage (TIA) 1. Thrombosis: occlusion of vessel by blood clot 2. Embolism: clot arises distally (usually heart) and travels to the brain. Further events may occur if source not identified Hemorrhagic subtypes (20% of strokes) 1. Subarachnoid hemorrhage (SAH): bleeding into CSF surrounding brain and spinal cord a. Symptoms: headaches (worst headache, thunderclap), nausea, visual disturbances, seizures, loss of consciousness if intracranial pressure sufficient 2. Intracerebral hemorrhage (ICH): bleeding directly into brain tissue a. Symptoms: weakness, tingling, paralysis (unilateral usually, trouble swallowing, visual problems, lose balance, trouble with language, confusion, apathy loss of consciousness b. Localized damage Cerebral artery infarctions - ACA and MCA supply >80% of cortex. Occipital lobe entirely - supplied by PCA ACA, MCA, PCA MCA Ischemic infarctions Contralateral hemiparesis (weakness) or hemiplegia (paralysis; tends to be face and upper extremities) - due to motor homunculus, these areas are more lateral Contralateral sensory loss Left hemisphere: aphasias Right hemisphere: left visual neglect ACA Ischemic infarctions Areas of necrotic tissue around midbrain contralateral weakness and sensory loss (legs more than upper extremity) Extreme changes in motivation: Abulia and mutism Gait apraxia: difficulty initiating gait, short shuffling movement Reduced speech output PCA Iscemic infarctions Hemianopia (unilateral blindness) and hemisensory loss Agnosias Memory loss Abrupt onset of difficulty seeing on right side Hemorrha ge Stroke on CT scan SAH - blood = white, around circle of willis, in CSF so blood gets circulated around brain - temporal, prefrontal Intracerebral: back, visual issue Structure-function relationships Cognitive outcomes of stroke/other brain injury Aphasias: 3 types - Aphasia = disruption in language affecting production or comprehension - Due to brain injury - most commonly due to stroke involving MCA - Morbidity and mortality worse in stroke when aphasia’s present - Some recovery but typically with residual deficits - 3 main kinds 1. Broca’s (expressive) a. Broca's aphasia or nonfluent aphasia refers to severe impairment in language production b. Usually due to damage BA 44/45 c. Grammatically complex sentences are most difficult to speak and understand d. Insight is good e. Diag: Damage to left inferior PFC (BA44/45), nonfluent speech, intact comprehension, impaired repetition, insight into difficulties i. Lady in hospital bed 2. Wernicke’s (receptive) a. Often occurs after damage to BA22 (temporal lobe) - superior temporal gyrus b. Typical characteristics: i. articulate/fluent speech - high word output - but frequent neologisms (made up words) and inappropriate words ii. Poor language comprehension - difficulty understanding spoken and written speech (esp. Nouns and verbs) iii. Less insight into problems c. Diag: damage to posterior STG (BA22), fluid but incomprehensible speech, impaired comprehension, impaired repetition, little insight into difficulties i. second man 3. Global a. Most severe form b. Patients produce few recognizable words and understand little or no spoken language c. Can neither read nor write d. Often seen immediately after the patient has suffered a stroke and may rapidly improve e. With greater brain damage severe and lasting disability may result f. Diag: widespread damage encompassing Broca and Wernicke areas; nonfluent, impaired comprehension, impaired repetition and insight i. First man Visual Agnosias: 6 conditions arising from cortical damage to visual areas - Ventral stream: vision for perception, identify objects - Dorsal stream: vision for action, pick up objects 1. Visual agnosia following damage to dorsal visual stream (stroke in PCA) a. Visual Neglect: issue with visual input b. Optic Ataxia: issues with visually guided action (reaching) c. Motion Blindness - rare i. Part of brain (Area MT) affected - similar vision as if there is a strobe light going 2. Visual agnosia following damage to ventral visual stream a. Prosopagnosia - cant recognize faces, most severe - cant recog children or family members faces b. Object Agnosia - cant put several cues together, think tennis racket is fencer mask bc they see criss cross lines c. Cortical Colour Blindness (unilateral lesion) - one hemisphere Neurodegenerative dementia Forms of neurodegenerative dementia - Dementia: objective decline in two or more cognitive or behavioural domains (memory, language, executive functions, visuospatial - Interferes with independence - Not due to other medical and psychiatric disorder - Global burden has increased: increased most in africa, then southeast asia, then americas, then europe - Most common causes of adult onset dementia - Alzheimers > cerebrovascular disease > lewy body disease [early disfunction in executive functioning, poor visuo spatial awareness, issues with driving, periods of severe cognitive lapses, excessive sleepiness, lucid periods, hallucinations]> frontotemporal dementia - Mixed dementia - mix of above Progression and pattern of atrophy in Alzheimer’s, how this affects cognition - Diagnosis of Alzheimer’s disease - Decline in episodic memory - recent memories affected first - May also feature or present with difficulties with: navigation, word finding, executive function - Gradual onset and progressive - Typical normal neurologic exam - Case: 78yo woman brought to clinic by family, noticed graudal onset and progressive lapses in recent memory. Repeat self several times an hour, gets lost in town, anxious, misplace objects around the house - Alzheimers: typical age of onset >65y - Pathologic deposition of amyloid plaques and neurofibrillary tangles (tau and phosphorylated tau) - Risk factors - Aging - Genetic: ApoE4, autosomal dominant mutations (APP, PS1, PS2) - Low educational/occupatoinal attainment - Family history of dementia - History of head injury - CV risk factors - Gender (female) at age 65 risk is 1 in 5 for women, only 1 in 10 for men - Neuroimaging - MRI or CT to rule out structural causes - Mesial temporal lobe atrophy - hippocampal atrophy - How Atrophy typically progresses in AD Prefrontla involvement, then lateral, then occipital areas, then visual disturbances Medial tmeporal region 1st (issues with memory first), 23: Neuropsychiatric DIsorders Review relevant functions of the prefrontal cortex - Dorsolateral Ventrolateral Rostral Orbitofrontal - overlap between this and ventromedial Dorsomedial Ventromedial Medial frontal cortex = some pink/green on right Nucleus accumbens, amygdala Prefrontal cortex: - Guides behaviour by internal representations, goals, and situational demands: not merely stimulus driven - Switching gears: changing behaviour when its not having desired impact - Emotion and social cognition: self-awareness, adaptive social behaviour, emotional control - Higher cognition: attention, working memory, planning Understand why prefrontal cortex “dysfunction” is so common - Dysfunction is among most common and least specific finding among neurological and psychiatric disorders - Frontal lobe dysfunction reflects more than direct damage to frontal lobes: ripple effects - PFC connection to other brain regions, modulates activity in other brain areas and modulates our behaviour - Could have axonal shearing - Ventromedial regions located in place where they are susceptible to injury (injury through orbital area, closed head injury) - Evolution/dissolution: Jackson: evolution is a passage from most simple to most complex, but when things break down goes from most complex to most simple - things that evolved earlier (brainstem) - more time to perfect themselves - PFC is recent - likely to have more problems (natural selection pressures) - Symptoms of PFC dysfunction - Attentional abnormalities - Poor planning and working memory - Language disturbances - Apraxia - Dysregulated affect an social disinhibition - Reduced empathy - Poor decision making - Confabulation - confused about where they encounter information - make up story - Changes in eating habits - Re-emergence of primitive reflexes - ex. Palmar reflex - Disorders with putative PFC dysfunction - Anxiety disorders - Psychopathy - Autism - Mood disorder - ADHD - Schizophrenia - Addiction - Conduct disorder - BPD - OCD - Intermittent explosive disorder Identify the basic architecture behind fear, anxiety, cue‐induced craving, and their regulation. [role of conditioning and extinction] - Anxiety Disorders - Feature excessive fear and anxiety, related behavioural disturbances - Most prevalent disorder 5-11% worldwide - More common in females than males 2:1 ratio - First line treatment: SSRIs (not benzos) and psychotherapy - Pharma-therapy may have higher effect size than psychotherapy Heritability of around 30% Common anxiety and related disorders - Specific phobia (7-9%): related to specific object or situation - Social anxiety disorder (7%): related to one or more social situations involving possible scrutiny - Panic disorder (2-3%): recurrent unexpecte panic attacks reaching peak within minutes - Generalized Anxiety Disorder (2/9-3/6%): persistent, excessive consistent worry about everyday issues - Trauma and stressor related disorders: PTSD (3.5%) - In each case, must: - Be clinically significant distress and impairment - Not better explained by another mental disorder or effects of a substance Key functional neuroanatomy of Post traumatic stress disorder - DSM-V diagnostic criteria 1. Exposure to threat of death, serious injury, or sexual violence a. As victim or witness or repeated exposure to aversive details (first responder) 2. Intrusion symptoms (reliving event) a. Recurrent memories, nightmares, flashbacks, intense distress at exposure 3. Persistent avoidance of stimuli associated with event a. Avoiding memories, people, places, things associated with event 4. Negative alterations in cognition or mood a. Inability to remember an important aspect of trauma b. Persistent negative beliefs about self or world c. Disinterest in events 5. Increased arousal and reactivity a. Irritability, hypervigilance, exaggerated startle, sleep disturbance - Flashbacks can be… 1. Visual: where trauma is reexperienced as visual images 2. Somatic: pain and bodily sensations resembling physical stimulation felt during trauma 3. Emotional: intense emotions are triggered similar to those felt during the trauma Addiction (Substance use disorders) - DSM-V includes 9 types: alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, stimulants, tobacco - Regardless of substance, based on pathological set of related behaviours (must show at least 2 over 12 mo period) - Impaired control: using more or for longer than intended, desire to reduce, cravings - - Social impairment: continued use despite problems with work, family, friends. Other activities given up in favour of substance - Risky use: fail to refrain despite harm (physical, psychological); use of substance when dangerous - Tolerance/withdrawal: increased use to achieve same effect Increasingly viewed as disorder featuring aberrant reward learning and reward related decision making Some symptoms explained by such deficits: - Continued use despite negative consequences - Impaired control over amount of use and drug seeking - Proneness to relapse Fundamental Mechanisms of emotional response acquisition and regulation - Fear conditioning: conditioned stimulus (tone), aversive stimulus (shock) - Now, scared everytime tone is scared alone. With repeated applications of the tone with no shock → extinction training - Little Albert (learning and anxiety) - Baby conditioned to be scared of rat (associated with loud noise) - generalized to white bunny, white fluffy coat, etc. - Fear can quickly generalize - A conditioned response to one object is exhibited in presence of similar stimuli - Generalization occurs with anxiety - Individual differences in tendency to generalize might be a key risk factor for development of anxiety disorder - Learning and generalization-related mechanisms in PTSD and addiction - War PTSD -- fireworkds - alch -- branding -- these cues go together [salivation/craving for drinking,] - Trigger for substance use disorder: paraphenalia, houses they did drugs in, people they did drugs with, bars they frequented - Function and dysfunction of amygdala - Key region for classical conditioning and fear learning - Emotional interpretation of external sensory information and internal states - Electrical stimulation elicits feelings of fear, irritability, even anger - Erbock Weitisim: calcifications bilaterally in amygdala patient - Amygdala: integrates information about aversive and fear associated stimuli to launch an immediate fear response - BNST: (bed nucleus stritate terminalis, extended amygdala) integrates information about about aversive and fear associated stimuli to generate a sustained fear response … uncertainty, sustained threat - Interacts with ventrostriation and nucleus accumbens for reward seeking behaviour - Changes in hippocampus related to treatment response - - - - Stress affects susceptibility to stress (at multiple levels) - Synaptic plasticity important for survival - Healthy fear and stress added - Can lead to healthy fear processing or pathological fear processing - Influenced by - Genetics and epigenetics - Cellular mediators - Synaptic plasticity* - Electrical properties - Local microcircuits* - Long-range projections* Acute stress has delayed effect on spine density of amygdala neurons - put rodent in restricted environment, causes stress - End up with behavioural changes - Elevated plus mase: closed/open arms - exploring open arm [unstressed explored more than stressed rodents. 10 days after acute stress barely explored) - took this long bc changes require time to occur - Golgi stained pyramidal neuron in BLA Effect of stress on neurons in amygdala - Before stress: normal Glu (+) input and GABA (-) input - Acute stress → increased cortisol, leading to increased Glu and less GABA (net increased firing of amygdala neurons (basolateral amygdala (BLA) - After stress: inc plasticity initiated by disinhibition - Temporal delay (days after stress) leads to high anxiety: see localized spinogenesis - With chronic or repeated stress, get considerable dendrite growth, extensive spinogenesis, cell is likely to respond in greater range of contexts. Conditioned response exhibited in multiple stimuli Amygdala is a hub, connects to numerous regions Role of PFC in mediating and extinguishing fear and addiction - Medial PFC can up or downregulate fear - Two primary division of mPFC - prelimbic PFC (PL) - prelimbic cortex which is rodent version of dACC, excitatory - - - Excites core part of accumbens, increase drug seeking - Excites BA in amygdala, increase fear response - Infralimbic cortex (IL) - rodent version of mPFC - Involved in reducing output. - Interacts with shell sector in accumbens to inhibit drug seeking - Interacts with ITC in amygdala to inhibit fear - *thought to play a role in extinction (repeated presentation of conditioned stimulus without aversive stimulus results in less of a response). Active extinction doesnt erase initial association, just suppressed - makes treatment harder - Both divisions connect to accumbens and amygdala - PL - Accumbens = reward centre. Extinction response only suppresses fear - Ex. person in bad car wrec - Exposure therapy: expose to trigger - imagine truck, then play sound of truck, then look at truck, then be passenger, etc. - Extinguish fear related response - Initial association isnt gone - know bc occasionally get reinstatement of fear - Can see this: person is fine in cues, all of a sudden get full blown response to stressor reemerges via reinstatement (exposed to trigger in a high stress environment - near miss with truck, right back to where he started) - This response is inhibited by mPFC mechanisms, not inhibited - If you only did training in office, only in that setting trigger is alleviated. Need to be out office too. - Spontaneous recovery - sometimes all of a sudden never had all therapy, back where they started - Same idea for drug addiciton trigger Stress impacts: - Amygdala - Persistent dendritic growth + Persistent spine formation - Hyper responsive - Correlated with symptom severity (PTSD) - Hippocampus (mental health role) - Reversible dendritic atrophy + reduced neurogenesis (stress is toxic) - Reduced volume - Volume Inversely correlated with symptom severity (small hippocampus = more severe symptoms) - - Reversal of volume loss = critical action for therapy. Some SSRIs take weeks before effects are seen, some effects are related to dendritic atrophy - Medial prefrontal cortex - Reversible dendritic atrophy - Reversible spine loss - Hyporesponsive Brain regions implicated in PTSD through functional neuroimaging - Increased reactivity in insular cortex Increased reactivity in dorsalmedial prefrontal cortex Reduced activity in ventral medial prefrontal cortex Hippocampal volume abnormalities
