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NEUROANATOMY REVIEW. February 24, 2006. BRODMANN’S AREAS. 8 = Frontal Eye Field 6 = SMA & Premotor ctx 5,7 = Post Parietal Ctx (apraxia, dom. side) 4 = Primary motor ctx 3,1,2 = Primary somatosensory ctx 41,42 = Primary auditory ctx (Transverse gyrus of Heschl)
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NEUROANATOMY REVIEW February 24, 2006
BRODMANN’S AREAS 8 = Frontal Eye Field 6 = SMA & Premotor ctx 5,7 = Post Parietal Ctx (apraxia, dom. side) 4 = Primary motor ctx 3,1,2 = Primary somatosensory ctx 41,42 = Primary auditory ctx (Transverse gyrus of Heschl) 44,45 = Broca’s speech area (Inf Frontal Lobe; expressive dysprosody) 22 = Wernicke’s speech area (arcuate fasciculus connect to Broca’s; receptive dysprosody) 40 = Supramarginal gyrus (Rt/Lt confusion, dyscalculia, agnosia) 39 = Angular gyrus (dyslexia & dysgraphia) Inf Parietal Lobe
PARIETAL LOBE(in addition to Area 3,1,2…general recognition such as ideas, patterns, symbols) Sup Parietal Lobe (either side) - contralateral sensory neglect (form of apraxia--constructional, dressing) Inf Parietal Lobe (Area 40, 39: Gerstmann’s syn on dominant side) - agnosia (prosopagnosia--faces, anosognosia--unaware of paralysis, Rt/Lt confusion) - dyscalculia (math), dyslexia & dysgraphia (reading & writing) - lower quadrantanopia (visual radiations to cuneus) Inf Parietal Lobe (Area 40, 39: usually for non-dominant hemisphere) - astereognosis (tactile agnosia) - apraxia (Areas 5-7, Post Parietal Lobule) - lower quadrantanopia (visual radiations to cuneus) TEMPORAL LOBE(HIPP, amygdala, auditory Area 41 42, Meyer’s loop) Parahippocampal Uncus = (deep to ctx lies amygdala) part of primary olfactory ctx. Mesial Temporal Sclerosis—seizures can have smell or visual aura.
Wernicke’s Encephalopathy (Thiamine/Vit B1 defic) 1) Nystagmus 2) Ataxia 3) Mental status change Korsakoff’s confabulatory syn 1) Mem loss & confabulation PAPEZ CIRCUIT HIPP Septal area Hypothal Fornix VAFP/VAPP (Ansa Lenticularis) Stria terminalis Fornix Ventral AmygdaloFugal Pathway Ventral AmygdaloPetal Pathway Mamillary body Amygdala Mamillothalamic tract Olfactory, Sensory, Autonomic Ant nuc of thalamus (MD) Ant limb of internal capsule Cingulate gyrus Perforant pathway Cingulum Entorhinal ctx
AMYGDALA Helps integrate complex sensory, emotional, and autonomic input for behavioral/emotional response. Output via Stria Terminalis posteriorly by tail of caudate and arches over thalamus to anterior hypothalamus. Output via Ventral Amygdalofugal Pathway (VAFP) to Caudate(BG)/Septal Area. 1. Central (integration of viscerosensory info with basal forebrain: septal nuc, nuc basalis of Meynert, & diagonal band of Broca) 2. Corticomedial (appetitive behaviors such as feeding, drinking, & reproduction with hypothalamus) 3. Basolateral (emotions, learning, & planning; with HIPP/limbic & BG) Klüver-Bucy Syndrome (bilateral ablation of ant temporal lobes containing amygdala) • Docility • Hypersexuality • Hyperphagia • Visual agnosia
HYPOTHALAMUS Homeostasis (autonomic, endocrine, & limbic systems)Can survive with half of hypothalamus
Ant Hypothal Nuc (“AH” dissipates heat, parasympathetic) Post Hypothal Nuc (conserves heat, sympathetic) Parvocellular PVN PVN & SON (produce oxytocin & ADH/vasopressin, destructionDI, PVNCRH) SUPRAOPTICO- HYPOPHYSIAL TRACT to post pituit Magnocellular PVN Preoptic area (Medial Preoptic Nuc) (sexually dimorphic, regulates gonadotropic hormones) Suprachiasmatic nuc (direct retinal input, circadian rhythms) OPTIC CHIASM Dorsomedial Nuc (stim causes obesity & savage behavior) Neuro- hypophysis Adeno- hypophysis Lat Nuc (appetite center, stim induces eating, destruction causes starvation) VMN Arcuate Nuc (DA-ergic neurons inhib prolactin release) TUBERO- HYPOPHYSIAL TRACT to ant pituit Ventromedial Nuc (VMN) (satiety center, stim stops eating, destruction causes obesity & savage behavior)
HYPOTHALAMIC FIBER SYSTEMS Fornix From HIPP to mamillary nuclei (then Mamillothalamic tract to Ant Thal Nuc) Medial Forebrain Bundle (MFB) • in lat portion of hypothalamus, lat to fornix • unmyelinated, major connection b/n cerebral ctx & BS • no synaptic relay through thalamus • receives monominergic neurons from the locus coeruleus (NE), raphé nuclei (5-HT), and ventral tegmental area (DA). Hypothalamo-spinal tract Descending autonomic fibers for sympathetic neurons (thoracolumbar lateral horn) and parasympathetic neurons (sacral lateral horn) Lesion or interruption above T1 can cause Horner’s syndrome (miosis, ptosis, anhidrosis, & apparent enophthalmos)
HYPOTHALAMIC FIBER SYSTEMS Stria terminalis… Stria terminalis--Amygdala to hypothalamus/septal area. STRIA = STRANDS (sup to fornix at border of caudate/thalamus) Lamina terminalis--from anterior commissure in rostral 3rd ventricle down to optic chiasm; closure of ant neuropore; anencephaly) LAMINA = LAYER Stria medullaris thalami--Habenular nuclei (in epithalamus) to hypothalamus/septal area (in 3rd ventricle roof inf to fornix; relay between midbrain reticular formation and limbic forebrain). STRIA = STRANDS, MEDULLARIS is also in the MEDULLA THALAMI lies completely on thalamus Stria medullaris of 4th ventricle--runs from arcuate nuc of pyramids (out through the central sulcus) to Inf Cereb Ped between Pons & Medulla. Sulcus Limitans--divides Alar & Basal plates. SULCUS = GROOVE
EMBRYOLOGIC DEVELOPMENT Neural Tube (CNS, pregang ANS) Neural Crest (PNS including DRG, postgang ANS) Sulcus Limitans SULCUS = groove (divides Alar & Basal plates) Alar plate (sensory) Basal plate (motor) Rhombencephalic lip (in roof of 4th ventricle becomes Cerebellum) Retinoic acid (Vit A) = expression of dev’tal genes like Hox (rostral-caudal segm.) Folic acid = prevent neural tube problems. SHH (Sonic Hedgehog) = notochord for dorsal/ventral axis.
EMBRYOLOGIC DEVELOPMENT Cephalic flexure Pontine flexure Cervical flexure PRIMARY VESICLES SECONDARY VESICLES Telencephalon (lateral ventricles) Prosencephalon Diencephalon (3rd ventricle) Mesencephalon (cerebral aqueduct) Mesencephalon Metencephalon (upper 4th ventricle) Rhombencephalon Myelencephalon (lower 4th ventricle, central canal)
THALAMUS BLOOD SUPPLY 1. PCA (post circulation) 2. PCOM (ant circulation) 3. Ant Choroidal (ant circulation)
Ant+MD/DM (Papez—limbic emotion) VA/VL (GP+SN—EPS motor) VPL (sensory--body) VPM (sensory--head) LGN (vision, Light) MGN (hearing) Pulvinar (sensory association) Intralaminar CM (diffuse to cerebral ctx, ends in layer I for cortical excit) Reticular (GABA-ergic to thal) = ANT-MED (limbic) = ANT-LAT (EPS) = POST (sensory) = NON-SPECIFIC (relay)
Caudate Caudate Fornix VA (VL) VA (VL) Ant Ant Interthalamic adhesion Cerebral peduncle Cerebral peduncle Mamillary bodies Ant Ant Pulvinar Pulvinar VL VL MD Pineal gland CM CM MD MD Sup colliculus LGN LGN VPL VPL MGN MGN VPM VPM Midbrain Zona Incerta STN Pons LD or DL LP
HIPPOCAMPUS HIPPOCAMPAL FORMATION (declarative mem)a) Dentate gyrus—HIPP input & output to HIPP pyramidal cells.b) Hippocampus properor Cornu Ammonis (CA)—to fornix then septal area.c) Subiculum—to fornix then mamillary nuc. Alzheimer’s Disease affects neurons in Nuc Basalis of Meynert (ACh), Locus Coeruleus (NE), Entorhinal ctx, and CA1/Subiculum of HIPP. MONOMINERGIC NUCLEI (connections with limbic system, HIPP) 1. Nucleus Basalis of Meynert (ACh) 2. Locus Coeruleus (NE) 3. Raphé Nuclei (5-HT) 4. Ventral Tegmental Area (DA), SNpc, Arcuate/tuberal nuc of hypothalamus SNpr (GABA)
Dentate gyrushas afferents & efferents entirely within HIPP formation. CA1 projects to Subiculum and pre-commissural FORNIX (to septal area).CA3projects to CA1 and pre-commissural FORNIX.CA4(hilus of dentate gyrus) receive afferents from dentate and projects to bilateral dentate gyri (via hippocampal commissure). Subiculumprovides main efferents to post-commissural FORNIX (to hypothalamus, thalamus, & mamillary bodies). HIPP proper
Pyr system (CS tract) Spastic Paralysis Flaccid Paralysis UMN lesion LMN lesion 1. Weakness 2. No atrophy 3. Inc tone 4. Inc DTR 5. Babinski STRENGTH MUSCLE TONE REFLEXES BABINSKI 1. Weakness 2. Atrophy (fasciculation/fibrillations) 3. Dec tone (hypotonia) 4. Dec DTR (hyporeflexia) 5. Downgoing toes Lesions above BS (c/l paralysis of face & body) Lesions at BS (crossed signs: i/l face, c/l body) Lesions below BS (no face involvement: hemisection causes crossed sensory signs, i/l touch etc, c/l pain & temp)
Pyr system (CS tract) Spastic Paralysis Flaccid Paralysis UMN lesion LMN lesion 1. Weakness 2. No atrophy 3. Inc tone 4. Inc DTR 5. Babinski STRENGTH MUSCLE TONE REFLEXES BABINSKI 1. Weakness 2. Atrophy (fasciculation/fibrillations) 3. Dec tone (hypotonia) 4. Dec DTR (hyporeflexia) 5. Downgoing toes EPS (Basal Ganglia) Cerebellum • Chorea (Huntington’s, Syndenham’s) • Athetosis (choreoathetosis in HD, Tardive dyskinesia when antipsychotics block DA receptors & make super-sensitive) • Hemiballismus (stroke to c/l STN) • Parkinson’s vs Diffuse Lewy Body Dz (bradykinesia, truncal instability, resting tremor, dementia) 1. Intention tremor 2. Ataxia (fall towards lesion, gait & trunk dystaxia, dysrhythmokinesia, dysdiadochokinesia, dysmetria) 3. Nystagmus 4. Dec DTR/tone ipsilaterally 5. Asthenia (mm tire easily)
Lenticular nuc = Put + GP Striatum/Neostriatum = Put + Caud Corpus striatum = Put + Caud + GP Glutamate GABA (Glycine in SC) Input from Ctx--Net excitation Input from D1 recep—Net excitation DIRECT PATHWAY Ctx Striatum GPi/SNr VA/VL thalamus Ctx Parkinson’s D1 recep SNc Input from Ctx—Net inhibition Input from D2 recep—Net excitation INDIRECT PATHWAY Ctx Striatum GPe STN GPi/SNr VA/VL thalamus Ctx Parkinson’s D2 recep SNc
Striatum(GABAergic neurons)--have both D1 recep (Gs; contain excitatory Substance P or dynorphin) & D2 recep (Gi; inhibitory Enkephalin or neurotensin). Net LOSS of excitation in Parkinson’s Dz. Pallidotomy destroys segments of GPi to reduce inhibition of thalamus (interrupts direct & indirect pathways). GPi and GPe tend to always be on/active. GPe is constantly on. In Huntington’s chorea, the striatum (ACh & GABAergic medium spiny neurons) are destroyed so GPe overstimulates Ctx. Damage to STN results in Hemiballismus due to decreased stim of thalamic inhibition to Ctx.
Cerebellar Peduncles 1. Sup Cerebellar Ped (cerebellum to cerebral ctx = dentatothalamic tract, VSCT) 2. Middle Cerebellar Ped (cerebral ctx to cerebellum = pontocerebellar fibers) 3. Inf Cerebellar Ped (spine to cerebellum = DSCT, CCT, OCT, vestibulocereb…JRB)
CEREBELLUM Functional vs Anatomical Divisions
Cerebellar Synonyms 1. VERMIS = Medial zone or (part of) Spinocerebellum 2.PARAVERMIS = Intermediate zone or (part of) Spinocerebellum 3.CEREBELLAR HEMISPHERES = Lateral zone or Cerebrocerebellum (or Pontocerebellum) 4.FLOCCULONODULAR LOBE = Vestibulocerebellum
Cerebellar Function 1. VERMIS = axial motor fxn; balance (Fastigial nuc) Spinocerebellum 2.PARAVERMIS = distal motor fxn/execution (Globose & Emboliform) Spinocerebellum 3.CEREBELLAR HEMISPHERES = motor planning (Dentate) Cerebrocerebellum 4.FLOCCULONODULAR LOBE = eye mvmt & balance; vestibulo-ocular reflex. Vestibulocerebellum
4 Cerebellar Deep Nuclei 5 Types of Cerebellar Cells (know if excit or inhib; know if they project out of cerebellum or not)
Cerebellar Deep Nucleireceive excitatory afferents from Climbing fibers and Mossy fibers (collaterals on their way to the Granule layer). Purkinje cell (only ones that project out of ctx) inhibitory fibers from Cerebellar Ctx to Cerebellar Deep Nuclei. Climbing fibers from Inf Olivary Nuc via Inf Cerebell Ped. Granule cell(only excitatory CELL) endings (Parallel Fibers) go to Molecular layer but not out of Cerebellar Ctx. Stellate, Basket, & Golgi cells (inhibitory) do not project out of Cerebellar Ctx either.
Flocculo-nodular lobe projects to Medial and Lateral Vestibular Nuclei. Medial Vestibular Nuclei assist coordinating eye movement with body. Lateral Vestibular Nuclei assist postural control. Don’t confuse Dentate nuclei (cerebellum) and Dentate gyri (HIPP).
Rubrospinal tracts (gross mvmts) cross immediately in midbrain. Rt cerebellum (Decussation of Sup Cereb Ped, then surrounds Red Nuc on BS slides) to Lt Red Nucleus (Rubrospinal tract) crosses to innervate Rt arm & leg. CEREBELLAR TESTS/SIGNS(cerebellum provides constant feedback & adjustment) 1. Posture/balance maintenance (DYSEQUILIBRUIM or TRUNCAL/GAIT ATAXIA) = fall towards affected side. 2. Voluntary motor activity/coordination (DYS-SYNERGIA) = finger-to-nose (intention tremor & dysmetria), pronator drift with poor adjustment, dysdiadochokinesia, foot tap/heel-shin, nystagmus on extreme gaze. 3. Helps in muscle tone maintenance (HYPOTONIA) *Romberg test = vision, vestibular, DC-ML. (not SC tract or cerebellum, which are for unconsc proprio).
BV’s & CN’s Pituitary adenoma Acoustic neuroma (Schwannoma) at CPA Berry aneurysms (ACOM, MCA, PCOM, basilar tip) asymptomatic unless large or rupture (possible death) rupture—SAH, hemorr stroke (seizures, HCP) worst HA of life (10/10) ADPKD, Ehlers-Danlos, Marfan’s
ICA-MCA aneurysm can put pressure on side of optic chiasm. Basilar tip aneurysm can put pressure on CN3’s. Lat striate or Lenticulostriate aa of cerebral hemorrhage (internal capsule). Occlusion of PCA distal to PCOM can result in Ant choroidal to Post choroidal aa. Labyrinthine a from AICA or Basilar a. Post Spinal a from PICA or Vertebral a.
Autoregulation allows constant blood flow over wide bp range (local metabolite control). Pupillary light reflex CN2 afferent & CN3 efferent. CN2 lesionpreserves consensual reflex. CN3 lesion causes blown-pupil (mydriasis), down-and-out eye, droopy eyelid, & no light reflex on affected side (no direct or consensual). Corneal blink reflex CN5 (V1) afferent & CN7 efferent. DTR’s Ankle jerk = S1 Knee ext = L2,3,4 Brachiorad = C5 Biceps = C6 Triceps = C7 Abdominal = T8-T12 Babinski = L5-S1
Internal Capsule BLOOD SUPPLY ANT LIMB = ACA (medial striate) + MCA (lateral / lenticulostriate) GENU = ICA (Ant Choroidal) POST LIMB = ICA (Ant Choroidal) + MCA (lateral / lenticulostriate) FIBERS ANT LIMB = cerebral ctx to/from thalamus (rest of Int Capsule too) GENU = CB tract POST LIMB = CS tract (A-T-L), DC-ML, ALS
1. Epidural lens 2. Subdural falx 3. Subarachnoid (ventricles) 4. Intraparenchymal bleeds Scalp infections down through valveless emissary vv. Pineal tumors (Perinaud’s syn) block cerebral aqueduct & impose on sup colliculus
HCP ex-vacuo (big ventricles, nml ICP, shrunken brain) NPH (big ventricles, nml ICP) Pseudotumor cerebri (nml or slit ventricles, inc ICP) Communicating vs Non-communicating Hydrocephalus (HCP) Above or below 4th ventricle Choroid plexus Creates CSF, Arachnoid villi/granulations Absorb CSF
HERNIATION SYNDROMES Subfalcine Transtentorial Foraminal
TEMPORAL NASAL TEMPORAL Ipsilateral blindness Nasal hemianopia Contralateral hemianopia with macular sparing Bitemporal hemianopia to LGN, optic radiations, then occipital lobe Contralateral hemianopia
LGN Crossed fibers to layers 1, 4, 6 Uncrossed fibers to layers 2, 3, 5 to LGN, optic radiations, then occipital lobe
Temporal lobe visual radiations (Meyer’s loop) to lingual gyrus Contralateral upper quadrantanopia LGN to OCCIPITAL LOBE Parietal lobe visual radiations to cuneate gyrus Contralateral lower quadrantanopia Calcarine fissure to LGN, optic radiations, then occipital lobe
Constricted field (glaucoma) Central scotoma (optic neuritis in MS) Lower altitudinal hemianopia (bilateral cuneate gyri) to LGN, optic radiations, then occipital lobe Upper altitudinal hemianopia (bilateral lingual gyri)
Sup Colliculus Vertical gaze MLF coordinates CN3 & CN6 (internuclear ophthalmoplegia in MS) • carries info from pontine Horizontal Gaze Centers (PPRF) to oculomotor complex in midbrain. • Helps during turning of head (conjugate gaze); inc activity during mvmt.
Voluntary Conjugate Gaze One-and-a-half Syndrome Argyll-Robertson’s pupils (syphilis) brachium of sup colliculus Optic radiation Visual ctx Rt Pontine Paramedian Reticular Formation (PPRF; lat gaze center) Lt Medial Longitudinal Fasciculus (MLF) Lt Area 8 (FEF) Rt CN6 Lt CN3 [Rt Gaze] Pupillary Light Reflex Optic n/chiasm/tract (CN2) Sup Colliculi (pretectal area) Ciliary ganglia (CN3 Edinger-Westphal) LGB Accommodation Optic n/chiasm/tract (CN2) Sup Colliculi (pretectal area) Ciliary ganglia (CN3 Edinger-Westphal) LGB
HEARING • Medial Sup Olivary Nuc (SON) is 1st place with binaural processing (ipsilat & contralat distribution to Lateral Lemniscus). Lesion after cochlear nuclei will decrease hearing bilaterally (more in contralateral ear). • Lateral Sup Olivary Nuc (SON) has intensity differences for horizontal position orientation. • The Inner hair cells transduce sound, and Outer hair cells modify sound(olivocochlear efferents). Scala media (endolymph—high K+). • The high frequencies are closest to Oval window/Stapes at the sound entry point(base of cochlea at scala vestibule and NOTround window at the end of the scala tympani)a.k.a. tonotopic organization, and high freq is dorsomedial in cochlear nuclei.
ANTEROGRADE degeneration is Wallerian degeneration—axons & myelin sheaths disappear. (e.g., Pt dies from mid-thoracic crush of spine. Stain of cervical spine shows Wallerian degeneration of…fasciculus gracilis.) • RETROGRADE degeneration is Chromatolysis—loss of Nissl substance (RER & free polyribosomes at cell body and dendrites are lost b/c axons no longer need NT) • In the CNS, glial scars formed by astrocytes inhibit healing(reactive astrogliosis). • For successful axonal repair, macrophages must clean debris. • 5. Axonal elongation is 2-4 mm/d in the CNS (oligodendrocytes) or PNS (Schwann cells). HEALING
Nerve Growth Factor (NGF) is a target-derived neurotrophic factor (peptide for DRG, ANS, and basal forebrain ACh neurons in CNS) • tropic (differentiation; turning toward stim) • trophic (growth & survival) • Other target-derived neurotrophic factors include…Neurotrophins (NGF, BDNF, NT3) and IGF1 + FGF + GDNF + CNTF + TGF-beta. • BDNF is synthesized in cell body & transported anterogradely down the axons (unlike NGF or GDNF). HEALING
Sensory neurons = Pseudounipolar, myelinated (DRG and CN 5, 7, 9, 10) Neurohistology Special senses = Bipolar (smell is unmyelinated-slow, hearing is myelinated-fast) (CN 1, 2, 8) Motor neurons = Multipolar (αMN, ANS)
AFFERENT (Layer IV is big in Brodmann Area 3,1,2) EFFERENT (Layer V is big in Brodmann Area 4) granular layers (II,IV = in) pyramidal layers (III,V,VI = out) Layer I (Molecular) Layer II (External Granular)—cortico-cortical fibers in. Layer III (External Pyramidal)—cortico-cortical fibers out. Layer IV (Internal Granular)—thalamocortical fibers in (VPL, VPM, LGN). Layer V (Internal Pyramidal)—CS/CB, & corticostriatal fibers out. (Betz giant pyramidal cells) Layer VI (Multiform)—corticothalamic fibers out. 6-Layered Neocortex
SENSORY & MOTOR HOMUNCULI Lots to lips, tongue, hand, & index finger Paracentral lobule = feet/legs
Rabies (Rhabdovirus) enters a peripheral nerve & travels retrograde to the DRG. Replicates/infects the CNS (encephalitis) with neurologic symptoms leading to coma & respiratory/cardiac arrest (fast retrograde transport via neurotubules & dynein: also herpes simplex virus, poliovirus, tetanus toxin). Retrograde Transport: RABIES
BRAINSTEM & SPINAL CORD February 24, 2006
Weber syndrome BRAIN STEM LESIONS MIDBRAIN(PCA, SCA, basilar) a) Weber (PCA) = CN 3 nuc + CB/CS tract b) Benedikt (PCA) = CN 3 nuc + CB/CS tract + ML + Sup Cereb Ped (a.k.a. paramedian midbrain syn) c) Parinaud (pineal tumor) = dorsal midbrain (defect in upward gaze) + HCP (a.k.a. dorsal midbrain syn) Wallenberg or Lat Medullary syndrome PONS(basilar, AICA) a) Millard-Gubler (basilar pontine br) = CN 6/7 + CS tract b) Med Inf Pontine (paramedian basilar) = CN 6 + CS tract + ML c) Lat Inf Pontine (AICA) = CN 5/7/8 nuc + ALS + Mid/Inf Cereb Ped + Hypothalamospinal tract Wallenberg syndrome Med medullary syndrome MEDULLA(vertebral, PICA) a) Med Medullary (vertebral) = CN 12 + ML + CS tract b) Wallenberg/Lat Medullary (PICA) = Nuc Ambiguus (CN 9/10/11) + ALS + SC tract