Cerebellum - Ron and Simon PDF

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Summary

Cerebellum (little brain)Has 2 main parts:  Outer cortex: 3 sub-divisions, which receive and integrate sensory and motor inputs: o Midline region = vermis o Lateral region = 2 hemispheres These 3 regions have grey matter on the outside and white matter inside and are deeply folded (like the cerebra...

Description

Cerebellum (little brain) Has 2 main parts:  Outer cortex: 3 sub-divisions, which receive and integrate sensory and motor inputs: o Midline region = vermis o Lateral region = 2 hemispheres These 3 regions have grey matter on the outside and white matter inside and are deeply folded (like the cerebral cortex) and they are concerned with events on the same side of the body (unlike the cerebral cortex).  Deep nuclei: send motor outputs o 3 pairs = fastigial, interposed and dentate. 3 paired cerebellar peduncles (axon pathways): The route in and out of the cerebellum –  Cerebellar cortex receives sensory and motor inputs via – inferior and middle cerebellar peduncles.  Sends results of the integration process via descending projections in the matter to the deep nuclei, which sends motor instructions via – inferior and superior cerebellar peduncles, which influence movement coordination. Cerebellar functions Involved in sensory-motor coordination, specifically:  Proper force and sequences of muscle contraction (timing).  Accurate movement sizes and amplitudes (space). Cerebellar lesions (damage) causes ‘ataxia’  Characterised by clumsy and misdirected movements: o Intention tremor and decomposition – mis-timing of muscles forces and contraction sequences.  Dysmetria – inaccurate movement amplitudes (over or under-shooting) Control of voluntary movements 3 distinct events, different brain regions: [1] Planning/Programming: • Pre-Motor Areas (PMA) of Frontal Cortex (includes Broca’s area)

• Contain stored motor programs, required to generate complex movement sequences (e.g. speech) [2] Initiation: • Primary Motor Cortex (M1) • Activates the Intended motor program [3] Execution: • Posterior Parietal Cortex (PPC) & the Cerebellum • Supervise & Coordinate movements in progress Sensory aspects of motor control The Motor Plan/Program: • Takes account of sensory information about current head, eye, body & limb positions. Execution of the Movement itself: • Generates sensory feedback, in different systems, for example: o Changes in head position (vestibular system) o Muscle contraction & joint positions (proprioceptive system) o Body parts moving in the field of view (visual system) The Cerebellum receives all this information – Calculates the best way to coordinate the timing, force & amplitude of the desired muscle contractions. Cerebellar cortex Has 3 main sub-lobes: • Midline = vermis + small medial extensions, the Flocculo-Nodular lobes. • Anterior lobe ( superior surface only) • Posterior lobe (superior surface and entire inferior surface) = largest and most lateral. Anterior and posterior lobes contain proprioceptive MAPS of the body and are separated by the ‘Primary Fissure’. Receives 2 types of input via the peduncles: • Motor plan/program: to all 3 sub-lobes o From inferior olive in the medulla. Which itself receives descending projections from the pre-motor and motor cortices. • Sensory information and feedback: to specific sub lobes o Vermis and FN lobe = from vestibular system for head position and head movements. o Anterior lobe = proprioceptive information about muscle tensions

and joint positions in all regions of the body, directly from the spinal cord and brainstem. o Posterior lobe = similar proprioceptive information, but from the somatosensory cortex and also visual information from the visual cortex (via cortical-pontine-cerebellar projections). The 2 types of input are received and integrated by Purkinje cells – present in each of the 3 sub-divisions and responsible for ‘motor error detection’. Purkinje cells In cerebellar cortex compare synaptic inputs: • From the inferior olive (motor plan) – axons called climbing fibres. • With sensory feedback specific to each sub0lobe from the movement in progress – via ‘mossy fibre’ input to granule cells then via axons called parallel fibres. Signal any mismatches or errors via their own axons to cells in the deep nuclei. 3 paired deep nuclei Purkinje Cells in the Cerebellar Cortex send orderly projections to specific deep nuclei on the same side of the brain: From Midline Vermis + FN Lobe: • To Fastigial Nucleus (medial, smallest) From Anterior Lobe: • To Interposed Nucleus (in-between) From Posterior Lobe: • To Dentate Nucleus (lateral, largest) Different outputs of the 3 nuclei: different aspects of movement coordination Fastigial, via Inferior Cerebellar Peduncle • To Vestibular Nuclei, origin of vestibulo-spinal tracts (for balance & posture) Interposed, via Inferior Cerebellar Peduncle • To Reticular Formation, origin of reticulo-spinal tracts (for gait, locomotion) Dentate, via Superior Cerebellar Peduncle • Red Nucleus, origin of rubro-spinal tract (for skilled movements, e.g., hand actions, speech) • To the Thalamus (Ventral Lateral Nucleus) & on to PreMotor & Motor Cortex (for up-dating motor plans).

Cerebellar Ataxia Damage to different regions of the cerebellar cortex may cause different impairments: 1. Vermis, FN and/or anterior lobes. Clumsy balance, posture, gait. 2. Posterior lobe Clumsy hand actions, slurred speech (dysarthria) and words in the wrong sequence (dysfluency).

Ocular innervation Sensory innervation • Trigeminal (5th) cranial nerve mediates touch, thermal and pain sensation: o Inside the eye – cornea and uveal tract. o Orbital contents and eyelids and conjunctiva. • Significance o Ocular pain: trauma, inflammation o Ocular defence: corneal-eye blink reflex Trigeminal nerve and face Map Upper-to-lower sensory territories: • Ophthalmic (V1): forehead, inside the eye, upper eyelid & orbital contents • Maxillary (V2): lower eyelid & orbital contents, cheek, upper jaw • Mandibular (V3): lower jaw Sensory innervation of the eye • Cornea has the greatest density of sensory receptors – many in uveal tract (iris, ciliary body and choroid) – attached to axons that run in the supra-choroid – exit the eye by penetrating the sclera posteriorly as short and long ciliary nerves. • Receptors present in the anterior epithelium – axons penetrate Bowman’s membrane – rich plexus of nerve fibres in the adjoining stroma – axons leave in all radial directions at the limbus. 3 ophthalmic nerve branches – all exit orbit via superior orbital fissure. 1. Nasociliary nerve: medial orbital path • Ciliary branches: Inside the Eye • Nasal branches: Inside the nasal cavity • Infra-trochlear: Medial upper eyelid + conjunctiva 2. Lacrimal nerve: lateral orbital path • Lateral upper eyelid + conjunctiva & Lacrimal Gland 3. Frontal nerve: upper orbital path • Forehead skin & scalp Trigeminal ganglion and nuclei These peripheral nerves contain axons of: • Trigeminal Ganglion Cells • Cell bodies located in Middle Cranial Fossa, depression in petrous

Temporal bone. • All central axons combine, forming the 5th Nerve Root, enters the lateral Pons. 2 Nuclei receive Uncrossed sensory input: • Pontine/Chief Nucleus: fine touch [1] • Spinal Nucleus: pain, thermal, crude touch [2] = analogous to [1] dorsal column/medial lemniscus & [2] spinothalamic tracts for the rest of the body. 3 parts of Spinal nucleus • Largest = caudal nucleus [1] o Extends, medulla to spinal cord (level C3), structurally similar to dorsal horn of spinal cord. o Map of pain and thermal sensation from ipsilateral face. • Smaller = oral and interpolar nuclei [2 and 3] o Situated in lower pons. o Receive crude (poorly localized) tactile sensations for corneal (eyeblink) and oral (salivation) reflexes. Protective corneal-eyeblink reflex 1. Sensory limb: light corneal touch • Activates receptors on corneal surface - axons via ciliary, naso-ciliary & ophthalmic nerves to trigeminal ganglion, then 5th Nerve Root to spinal Nucleus of V (Interpolar & Oral nuclei). 2. Motor limb: close eyelids • Somatic motor neurons in main facial nucleus – axons run in facial nerve, then via temporal & zygomatic branches to contract orbicularis oculi. Motor innervation Facial (7th) Cranial Nerve supplies voluntary muscles around the eye: • Eyelids: Orbicularis Oculi • Other Peri-Orbital: frontalis, corrugator, procerus + Parasympathetic: Lacrimal gland, via Pterygopalatine Ganglion (increased tear flow). Oculomotor* (3rd), Trochlear (4th) & Abducent (6th) • Extra- Ocular muscles: Eye movements + Parasympathetic*: sphincter & ciliary muscles, via Ciliary Ganglion (pupil constriction & accommodation).

Facial nucleus and nerve 3 distinct Components, all Uncrossed: 1. ‘Main’ Motor o Somatic: innervates voluntary (skeletal) muscles of facial expression 2. ‘Parasympathetic’ Motor o Autonomic: innervates Ganglia supplying different glands (lacrimal, salivary) 3. Special sensory o Taste sensation, anterior 2/3rds of tongue • Main 7th motor nerve loops around the Abducens nucleus (forming bump = facial colliculus) before exiting the brainstem with the Nervus Intermedius (NI) which carries the parasympathetic and sensory (taste) axons. Main facial nerve pathway • Axons from the Main Facial Nucleus initially loop around the Abducens Nucleus – exit ventral brainstem: pons-medulla junction (between 6th & 8th Cranial Nerves). • Enter petrous temporal bone via internal auditory meatus & exit posteriorly via stylo-mastoid foramen. • Descend to parotid gland & splits into 5 branches – Temporal, Zygomatic, Buccal, Mandibular, Cervical – supplying upper-to-lower facial muscles (map). Facial nerve and tear production Parasympathetic Pathway: • Autonomic Motor neurons, Superior Salivatory Nucleus • Pre-Ganglionic Fibres: Nervus Intermedius follows Main 7th Nerve into petrous temporal bone • But exits anteriorly to end in Pterygopalatine Ganglion • Post-Ganglionic Fibres innervate the Lacrimal Gland • Secreto-Motor function: stimulate gland cells, increase tear production (e.g., counteract excess evaporation) Clinical aspects 1. Irritation & Facial Muscle Spasm • Usually Main Facial Nerve only at stylo-mastoid exit.

2. • • •

• Blepharospasm: frequent, forcible & uncontrolled eyelid closures (treatment, botulinum toxin injections in OO). Lesions & Bell’s Palsy Can involve both Main Facial & Nervus Intermedius Paralysis all muscles of facial expression Lagophthalmia (staring, open eye) + Ectropion (everted lower eyelid) + Dry eye (reduced tears): erosion & ulceration of outer corneal epithelium affects vision.

Treatments 1. Upper Eyelid Palsy = insert gold weight • Eye kept open, by voluntary contraction of LPS • Relax LPS, eye closes by force of gravity 2. Everted Lower Eyelid = tighten surgically • Creates a lateral pool of tears • Reduce lower lid length prevents drooping 3. Dry Eye = lubricating drops or ointments • Moisture chamber shields attached to spectacle frames, lessens tear evaporation

Ocular Pain 2 types of sensory receptor In most body tissues (including ocular): 1. Free nerve endings • Pain or temperature sensitive 2. Specialised mechanoreceptors • Tactile receptors (touch, pressure) • Proprioceptors Pain stimuli Transduced by nociceptors, respond to tissue damage caused by: • Mechanical deformation (pinch, cut) • Temperature extremes (heat, cold) • Chemical irritants (acid) Many nociceptors are poly-modal = activated by each type of potentially harmful stimulus. Types of pain sensation Different nociceptors signal: 1. Sharp, stabbing, sticking (heat) pain • A-fibres: small axons, thinly myelinated 2. Dull, aching, throbbing, stinging pain • C-fibres: small axons, unmyelinated Corneal and uveal receptors Revealed by electrophysiological recordings from their axons in the ciliary nerves leaving the eye: • 50% mechanoreceptors (touch, pressure) o Phasic (fast-adapting) responses to mechanical stimulation • 50% poly-modal nociceptors o Tonic (slowly-adapting) responses to noxious mechanical, thermal & chemical stimuli o 33% A(sharp) & 66% C (dull, throb, sting) Pain pathways from eye to brain (trigeminal nuclei) o Receptors in anterior cornea epithelium & uvea o Axons run in supra-choroid o Exit posterior eye via short & long Ciliary Nerves o Join Naso-ciliary branch of Ophthalmic Nerve

o Join 2 other divisions of Trigeminal (V) Nerve o Axons terminate in the (main) Caudal division of Spinal Nucleus of V o Touch fibres also terminate in the Interpolar & Oral divisions (sensory limb, corneal reflex) Ascending pain pathways Perception (pain quality & location)  Crossed, Trigemino-Thalamic Tracts to Ventral Posterior (VP) nucleus of thalamus  VP connects to Primary Somatosensory Cortex, Post-Central Gyrus (Parietal lobe) Arousal & Affect (emotional context)  Crossed, Trigemino-Reticular Tracts to several brainstem nuclei, including the Peri-Aqueductal Grey (PAG) in midbrain Pain localisation 1. Cutaneous (skin) tissue o 1 compact, free nerve-ending per axon o small ‘receptive fields’, no overlap o accurate localisation of noxious stimuli 2. Visceral (deep) tissues (eye) o Many, widespread endings per axon o Large ‘receptive fields’ overlapping o Poor localistaion of noxious stimuli Ocular, orbital and/or peri-orbital pain Can occur in 2 different ways: 1. Direct pain – damage within the affected tissue itself 2. Indirect pain - damage to the nerve supply – not the actual tissue 3. Referred pain – damage is elsewhere and incorrectly localised Direct ocular pain Naturally-occurring:  Dry Eye (corneal irritation)  Conjunctivitis (infection)  Uveitis & Orbital Cellulitis (infection)  Glaucoma (raised IOP)  Tumours (e.g., melanoma) Latrogenic:  Eye Drops (e.g., atropine) and Laser surgery (e.g., iridectomy).

Anterior uveitis – iris and ciliary body Deep dull pain:  Autoimmune, microbial  T-cell mediated  Release histamine  Spread via from uvea via anterior iridial circle  Steroids: immune suppression and anti-inflammatory Indirect ocular pain Inflammatory causes:  Retro-bulbar Optic Neuritis  Herpes Zoster Ophthalmicus Other causes:  ‘Phantom’ Eye: post-enucleation (e.g., tumour)  Trigeminal Neuralgia: - Brief, but excruciating: affects territories one or more of the 3 trigeminal nerve branches - Cause unknown: but may be provoked by tactile stimulation of ‘trigger zone’ suggesting nerve hyper-excitability - Treatment: cauterize affected nerve or make small lesion in medulla to destroy pain fibres, leaving fine touch & corneal reflex intact Referred ocular pain Remote causes, with headache too:  Dura Inflammation (meningitis)  Arterial Circle of Willis distortions (aneurysms or arthero-sclerosis, brain tumours) How? = Trigemino-vascular axons:  Pain receptors in the dura & large artery walls attached to branched axons that also have branches coming from pain receptors in the eye so the brain cannot distinguish between stimulation of the dura/arteries & ocular tissues. Pain modulation Mechanisms for reducing transmission in the Ascending pain pathways:  Analgesics: opiates o Activate endogenous endorphin (opioid) receptors  Local control via inhibitory interneurons

o Trans-Cutaneous Electrical Nerve Stimulation (TENS)  Descending noxious inhibitory control (DNIC) o Deep-Midbrain PeriAqueductal Grey (PAG) Stimulation Wholebody, rather than local, analgesia...