Neurological System PDF

Neurological System Gabin: [email protected] PSPANDA Kevin: [email protected] Elina: [email protected] JJ: [email protected] PSPanda ...

Neurological System Gabin: [email protected] PSPANDA Kevin: [email protected] Elina: [email protected] JJ: [email protected] PSPanda  Neuroembryology Gabin: [email protected] The Nervous System Complex collection of specialized neurons which transmit signals between different parts of the body: Central NS ○ Brain Prosencephalon Cerebrum = telencephalon ○ Cerebral cortex - frontal, parietal, temporal and occipital lobe ○ Subcortical structures - basal ganglia, hippocampus, amygdala (limbic system) ○ Corpus callosum Diencephalon = thalamus and hypothalamus Mesencephalon Rhombencephalon Medulla = myelencephalon Pons = metencephalon Cerebellum ○ Spinal Cord - begins at occipital bone ○ Nerves Peripheral NS ○ Nerves ○ Ganglia Neurulation Early Week 3 Appearance of notochord within mesoderm causes overlying ectoderm to thicken and form the neural plate Late Week 3 Lateral edges of the neural plate elevate to form neural folds and approach each other in the midline ○ Depressed mid-region forms = neural groove ○ Fusion of folds begins cervically and continues cranially and caudally → formation of neural tube Neural tube cells → motor neurons and glial cells Neural crest cells → Schwann cells, adrenal medulla, sympathetic and parasympathetic ganglion, melanocytes, dorsal root ganglion Week 4 & 5 Week 4 Dilation of the cranial end of the neural tube → formation of 3 primary vesicles ○ Prosencephalon ○ Mesencephalon ○ Rhombencephalon Week 5 (5 parts in Week 5) Further division of these 3 divisions to form 5 secondary vesicles ○ Prosencephalon → telencephalon (cerebrum) + diencephalon ○ Mesencephalon remains same (midbrain) ○ Rhombencephalon → metencephalon (cerebellum and pons) + myelencephalon (medulla oblongata)  Neuroanatomy Gabin: [email protected] Prosencephalon Anterior-most portion of the brain comprised of 2 hemispheres with 4 lobes each Functions: ○ Body temperature ○ Reproductive functions ○ Eating ○ Sleeping ○ Display of emotions Composed of grey and white matter (as well as the rest of the CNS) ○ Grey matter = neuronal cell bodies Outside/ external surface Contains cerebral nuclei ○ White matter = neuronal cell axons (fibre tracts) Inside/ internal surface Major Gyri and Sulci Central sulcus Precentral gyrus Separates primary motor area of frontal lobe Primary motor area (pre-frontal gyrus) from the primary sensory Post-central gyrus area of the parietal lobe (post-frontal gyrus) Primary sensory area Pre-central sulcus Cingulate gyrus Post-central sulcus Part of limbic system Lateral sulcus (Sylvian fissure) Located on medial aspect of brain When pulled apart, reveals the insular lobe Responsible for emotion and behaviours Middle cerebellar artery exits through lateral Rectal gyrus sulcus Parieto-occipital sulcus Divides parietal and occipital lobes Orbital sulcus ‘H-shaped’ Olfactory sulcus Transmits olfactory nerve (CNI) Frontal Lobe Primary motor cortex (precentral gyrus; Brodmann area 4) ○ Anterior to the central sulcus ○ Most basic information originates here and is processed peripherally ○ Organisation forms the motor homunculus Anterior association centre whose functions include: ○ Concentration, executive functioning (organisation, planning and flexibility), working memory, speech (Broca’s area) behaviours, intellect, judgment, emotional expression, creativity, inhibition Olfactory area Broca’s area (controls muscles of speech to combine sounds into words) Parietal Lobe Primary somatosensory cortex (postcentral gyrus; Brodmann area 3,1 &2) ○ Posterior to the central sulcus ○ Organisation forms the sensory homunculus ○ Touch, pain, temperature sensation Somatosensory unimodal association cortex Angular gyrus ○ Mathematics ○ Language ○ Spatial recognition ○ Memory retrieval Supramarginal gyrus ○ Language perception and processing Temporal Lobe Involved in hearing, naming of objects, formation and management of memory as well as visual recognition Limbic association area ○ Learning and memory ○ Emotions - links emotions with sensory info Wernicke’s area (sensory speech area) ○ Functions in written and spoken language comprehension Primary auditory cortex ○ Hearing ○ Damage will cause deafness but reflexive reactions to sound persists ○ This is because loud sounds is processed by subcortical processes Secondary auditory cortex Occipital Lobe Visual cortex - receives visual input (colour, light and movement) Supplied by posterior and middle cerebral arteries Limbic Lobe Arc-shaped region of cortex on the medial surface of each cerebral hemisphere Involved in motivation, emotion, learning and memory Cingulate cortex = cingulate gyrus + cingulate sulcus ○ Part of the limbic system, which also includes Basal ganglia Amygdala Hippocampus Thalamus ○ Affected in disorders such as depression and schizophrenia Insula Portion of the cerebral cortex folded deep within the lateral sulcus (fissure separating temporal from parietal and frontal lobes)  Basal Ganglia Group of subcortical nuclei which are situated at the base of the forebrain and top of the midbrain, responsible for a variety of functions: Voluntary movement Habit Emotion Learning Components of the Basal Ganglia Lentiform nucleus = large cone-shaped mass of grey matter lateral to the internal capsule. Divided into the: Putamen (most lateral) Globus pallidus (most medial) ○ GP internus ○ GP extrenus Caudate nucleus Located lateral to the lateral ventricle ○ Head forms lateral impression in lateral ventricle ○ Large head and small tail Joined anteriorly with the putamen but separated by the internal capsule posteriorly Amygdala Components of the Basal Ganglia Subthalamic nuclei Nucleus located ventral to the thalamus and medial to the internal capsule. Substantia nigra Degeneration is implicated in Parkinson’s disease 2 subdivisions ○ SNc = substantia nigra pars compacta Contains a large amount of dopaminergic neurons Dark colour comes from neuromelanin ○ SNr = substantia nigra pars reticulata Functionally related to GPi GABAminergic projections Diencephalon Thalamus Surrounds the 3rd ventricle, superior to the midbrain Interthalamic adhesion = flattened band of tissue that connects both parts of the thalamus at their medial surfaces Significant thalamic nuclei ○ Medial geniculate body = relay centre for auditory pathway ○ Lateral geniculate body = relay centre for visual pathway ○ Both are lateral to the superior colliculus Hypothalamus Situated inferior to the thalamus Mamillary body = 2 bulges of the thalamus on the inferior surface of the brain ○ Function related to memory White Matter Structures Corpus callosum Broad band of nerve fibres joining the 2 hemispheres of the brain ○ Inferior to the cingulate gyrus ○ Subdivided into: Rostrum Genu - anterior bend Trunk/ Body Splenium - posterior bulge 3 groups of fibres ○ Fibres connecting 2 cerebral hemispheres ○ Fibres connecting frontal and occipital lobe ○ Fibres moving from cortex to spinal cord White Matter Structures Anterior commissure White matter tract connecting both temporal lobes, travelling through the corpus callosum Posterior commissure White matter tract travelling behind the cerebral aqueduct Important in bilateral pupillary light reflex White Matter Structures - Capsules Internal capsule Separates the caudate nucleus and thalamus from the lentiform nucleus Carries information past the basal ganglia via both ascending and descending fibres Subdivided into: ○ Anterior limb ○ Genu ○ Posterior limb Components: ○ Frontopontine tract = fibres from frontal cortex → pons ○ Anterior thalamic radiation = fibres from thalamus → frontal lobe cortex ○ Corticobulbar tract = tract from cerebral cortex → brainstem Carries motor fibres of non-oculomotor nerve cranial nerves to respective cranial nerve motor nuclei ○ Corticospinal tract = pyramidal tract carrying UMN down the spinal cord ○ Corticorubral tract = tract extending from frontal lobe cortex → red nucleus ○ Posterior thalamic radiation = fibres from thalamus → parietal lobe cortex (general sensation) White Matter Structures - Capsules External capsule Fibres running between the most lateral segment of the lentiform nucleus and the claustrum Extreme capsule Provides bidirectional communication between the: ○ Claustrum and insular cortex ○ Inferior frontal gyrus (Broca’s area) and middle-posterior portion of the superior temporal gyrus (Wernicke’s area) White Matter Structures Fornix C-shaped bundle of fibres in the brain which carries signals from the hippocampus to the mammillary bodies and anterior nuclei of the thalamus Part of the limbic system Optic chiasm Site of partial crossing of the optic nerves Located at the bottom of the brain immediately below the hippocampus and above pituitary gland Other Structures Claustrum = slip of grey matter between the external and internal capsule Lamina terminalis = thin lamina which stretches from the interventricular foramen of Monro to the recess at the base of the optic stalk (embryological origin of optic nerve) Contains the organum vasculosum of the lamina terminalis which regulates osmolarity in the blood Pituitary gland Pea-sized gland which sits in the bony enclosure (sella turcica) - enclosed in a dural fold (diaphragma sellae) ○ Protrusion off the bottom of the hypothalamus Composed of 3 lobes ○ Anterior lobe ○ Posterior lobe Functionally connected to the hypothalamus via the media eminence and pituitary stalk (infundibulum) ○ Intermediate lobe Secretes melanocyte-stimulating hormone  Other Structures Amygdala Two almond-shaped groups of nuclei located deep and medially within the temporal lobes Role ○ Processing of memory ○ Decision making ○ Emotional reactions Part of the limbic system Hippocampus Belongs to the limbic system Roles ○ Consolidation of information from short-term to long-term memory ○ Spatial navigation Located under the cerebral cortex lateral to the amygdala and caudate nucleus Contains 2 main interlocking parts ○ Ammon’s horn ○ Dentate gyrus Degeneration in Alzheimer’s disease ○ Memory loss ○ Disorientation Damage to the hippocampus can also result from hypoxia, encephalitis, medial temporal lobe epilepsy Extensive, bilateral hippocampal damage in individuals may result in anteretrograde amnesia (inability to form and retain new memories) Cerebrospinal Fluid Clear colourless fluid found in the brain and spinal cord Location: ○ Within the subarachnoid space - between the pia mater and arachnoid mater ○ Inside 4 ventricles Functions: ○ Protection ○ Removal of metabolic waste ○ Chemical stability ○ Prevention of brain ischaemia CSF Inputs and Outputs Inputs Produced predominantly in the lateral ventricles which contain the choroid plexus which filters and creates CSF ○ Lateral ventricles are separated by the septum pellucidum CSF travels → 3rd ventricle via the interventricular foramina of Monro ○ Interthalamic adhesions connecting 2 thalami is surrounded by the 3rd ventricle CSF travels → 4th ventricle via cerebral aqueduct CSF moves into subarachnoid space after passing the 4th ventricle Passes down and back up the spinal cord before enveloping the brain superior Output Absorbed through arachnoid granulations in the walls of dural venous sinuses Drains and empties into the internal jugular vein Meninges The brain is covered by 3 layers of meninges which from superficial to deep are: Dura mater Arachnoid mater Pia mater Epidural space Space between cranium and dura mater Dura Mater Consists of 2 layers: ○ Periosteal layer (superficial) - this layer is not present in the vertebral column ○ Meningeal layer (deeper) The meningeal layer reflects upon itself → formation of inward foldings known as dural reflections ○ Falx cerebri - separates the 2 cerebral hemispheres ○ Tentorium cerebelli - separates the cerebellum and brainstem from occipital lobe ○ Falx cerebelli - sagittal reflection inferior to the tentorium cerebelli ○ Diaphragm sellae - forms a partial roof over pituitary gland The dural venous sinuses which drain the brain are contained between these 2 layers Dural Venous Sinuses Collecting pools of blood which drain the CNS, face and scalp which lie between the periosteal and meningeal layers of the dura mater All of the dural venous sinuses ultimately drain into the internal jugular vein Valveless Dural Venous Sinuses The superior sagittal sinus, inferior sagittal sinus and straight sinus (all contained within falx cerebri) converge at the confluence of sinuses (overlies internal occipital protuberance) Separates into transverse sinus bilaterally → curves into sigmoid sinus ○ Sigmoid sinus and inferior petrosal sinus converge to form the internal jugular vein ○ Petrosal sinuses drain the cavernous sinus Other Layers of the Meninges Arachnoid mater Avascular and aneural Arachnoid granulations = small projections of arachnoid mater into the dura mater which allow for CSF to enter the dural venous sinuses and drain into the IJV Subarachnoid space Contains CSF - functions as part of the blood brain barrier Pia mater Highly vascularised Tightly adhered to the surface of the brain Veins of the Cerebrum Responsible for drainage of the brain tissue and deposition into the dural venous sinuses ○ Travel through subarachnoid space and pierce the meninges to drain into the dural venous sinuses Superficial ○ Superior cerebral veins - drains superior surface → superior sagittal sinus ○ Superficial middle cerebral vein - drains lateral surface → cavernous or sphenopalatine sinuses ○ Inferior cerebral veins - drain inferior surface → cavernous and transverse sinuses ○ Superior anastomotic vein - connects the superficial middle cerebral vein → superior sagittal sinus ○ Inferior anastomotic vein - connects the superficial middle cerebral vein → transverse sinus Deep ○ Subependymal veins - receive blood from medullary veins → dural venous sinuses ○ Medullary veins - originate 1-2 cm below the cortical grey matter → subependymal veins Brodmann’s Areas Brodmann numbers are assigned to regions of the cortex of the brain according to its architecture. Areas of particular significance are: Area 4 = primary motor cortex (precentral gyrus) ○ Involved in simple movements Area 6 = premotor area/ supplementary area ○ PMA = involved in sensory-guided movements and control of proximal and trunk muscles ○ Proper SMA = planning of motor actions, especially those guided by memory ○ Pre-SMA = acquiring new motor skills Brodmann’s Area Area 3,1,2 = primary somatosensory cortex (post-central gyrus) ○ NB: ordered anteriorly and posteriorly ○ Area 3 = touch (nociception, light touch and deep pressure) ○ Area 1 = texture ○ Area 2 = size and shape Area 5 and 7 = posterior parietal cortex ○ Integrates sensory information to create an internal representation to the body ○ Area 5 = receives somatosensory information from primary somatosensory cortex ○ Area 7 = receives visual and proprioceptive information Area 17 = primary visual cortex Area 44 and 45 = Broca’s area Area 22, 29 and 40 = Wernicke’s area Area 41, 42 = primary auditory cortex Brain Dominance Brain dominance is determined by which side of the brain Wernicke’s and Broca’s areas are on: Most people are left brain dominant ○ 90% of right-handed people are left-brain dominant ○ 50% of left-handed people are left-brain dominant This is significant in strokes as can identify whether there will be any speech impairment due to infarction Broca’s/ Wernicke’s area Aphasia Aphasia = impairment in language production or comprehension brought on by neurological damage Broca’s aphasia ○ Non-fluent aphasia/ expressive aphasia ○ Decreased verbal expression ○ Speech perception is not affected ○ Language comprehension is normal Wernicke’s aphasia ○ Deficits in comprehension of language/ receptive aphasia ○ Fluent speech ○ Word salad Brainstem Composed of structures of the midbrain (mesencephalon) and hindbrain (rhombencephalon) and continuous with the spinal cord posteriorly Midbrain Medulla oblongata Pons Note cerebellum, although cerebellum is a rhombencephalon structure, it is not part of the brainstem Functions include: cardiac and respiratory control, regulation of circadian rhythms, cranial nerve supply, conveyance of motor and sensory pathways Midbrain Pineal gland Small endocrine gland Part of the epithalamus Produces melatonin - serotonin derived hormone which affects modulation of sleep pattern in seasonal and circadian rhythms Infundibulum Connection between the hypothalamus and posterior pituitary gland Midbrain Tectum Involved in visual and auditory reflexes Sits on the dorsal aspect of the midbrain - composed of corpora quadrigemina Superior colliculus (2) ○ Site of termination of 10% of visual afferent fibres, ○ Sends information to the lateral geniculate nucleus Inferior colliculus (2) ○ Principle midbrain nucleus of the auditory pathway ○ Receives input from auditory cortex and peripheral brainstem nucleus ○ Sends auditory information to the medial geniculate nucleus Midbrain Cerebral aqueduct Connects the 3rd ventricle in the diencephalon to the 4th ventricle within the region of the medulla and pons Tegmentum Portion of midbrain ventral to the cerebral aqueduct Communicates with the cerebellum via superior cerebellar peduncles Conducts various tracts including medial lemniscal pathway, spinothalamic tract rubrospinal tract Midbrain Periaqueductal gray Primary control center for descending pain modulation Contains enkephalin-producing cells which suppress pain Located around the cerebral aqueduct within the tegmentum of the brain Substantia nigra Subcortical structure involved in reward, addiction and movement via dopamine Pons Brainstem structure which lies inferior to the midbrain, superior to the medulla oblongata, and anterior to the cerebellum ○ Separated from the midbrain and medulla oblongata via the inferior pontine sulcus and superior pontine sulcus respectively Conducts motor and sensory signals via tracts Can be divided into ventral and dorsal pons Vasculature ○ Basilar artery runs down the midline of the ventral surface through the basilar groove ○ Supplied by largely by pontine arteries - arising from basilar artery but also AICA and PICA Pons Function = CN V-VIII functions, respiration, relaying signals Cerebral peduncles Contain ascending and descending nerve tracts from the cerebrum to the pons ○ Occipito, parieto, temporo, frontopontine tracts ○ Corticospinal tract ○ Corticobulbar tract Essentially contains all structures of the midbrain except tectum Cerebral crus = anterior-most portion of the cerebral peduncle Medulla Oblongata Function = contains respiratory, vomiting, cardiac and vasomotor (autonomic) centres Anterior protrusions Olivary bodies = contains olivary nuclei, made of 2 parts: ○ Inferior olivary nucleus Part of the olivo-cerebellar system and is mainly involved in cerebellar motor-learning and function Sends ascending fibres to the cerebellar cortex ○ Superior olivary nucleus Considered part of the pons and auditory system Aids perception of sound Pyramids ○ Contain motor fibres of the corticospinal and corticobulbar tract Medulla Oblongata Posterior features Structures within the rhomboid fossa ○ Medial eminence and sulcus ○ Facial colliculus - formed by fibres from the motor nucleus of the facial nerve as they loop over the abducens nerve ○ Vestibular area ○ Hypoglossal trigone ○ Vagal trigone Mainly contains nuclei of the cranial nerves Medulla Oblongata Posterior features Gracile tubercle and fasciculus - posteromedial ○ One of the dorsal column nuclei that participates in the sensation of fine touch and proprioception of the lower limb ○ It contains second-order neurons of the dorsal column-medial lemniscus pathway, which receives inputs from sensory neurons of dorsal root ganglia and sends aconds which synapse in the thalamus Cuneate tubercle and fasciculus - lateral to the gracile tubercle and fasciculus ○ Part of the dorsal column-medial lemniscus pathway, carrying fine touch and proprioceptive information from the upper limb (above T6, except the ear and face which is carried by the trigeminal nucleus) to the contralateral thalamus via the medial lemniscus Tuberculum cinereum (spinal tract of the trigeminal nerve) Cranial Nerves General principles Cranial nerves emerge directly from the brain and brainstem, in contrast to spinal nerves which emerge from segments of the spinal cord Unlike spinal nerves, cranial nerves do not cross over to supply the other side of the body Classifying cranial nerves General or special (G/S) ○ General = the structure associated with a function that is applicable to anywhere in the body ○ Special = the structure of a pharyngeal arch derivative ○ Special = the structure associated with a function special to the head and neck Somatic or visceral (S/V) ○ Is the structure going to a somatic or visceral structure All nerves associated pharyngeal arch structures are considered visceral innervation (even those supplying somatic muscle) - this is because pharyngeal arches are a gut tube derivative Afferent or efferent (A/E) ANS and the Cranial Nerves Sympathetics (originating T1/2 - L3) Originate at the intermediolateral nucleus of the lateral grey column Exit via the ventral horn After exit, nerves enter the sympathetic trunk via the white matter communicans ○ Nerves can exit the sympathetic trunk at the same or another level via grey rami communicans Sympathetic nerves can either synapse within the sympathetic trunk or one of the cervical ganglions  ANS and the Cranial Nerves Parasympathetics (originating in brain or sacroiliac region) Originate within the following cranial nerves ○ Oculomotor (3) ○ Facial nerve (7) ○ Glossopharyngeal nerve (9) ○ Vagus nerve (Does not supply any parasympathetic innervation to head and neck structures) (10) Usually synapse at the target organ, except in the target organ where they synapse at on of 4 paired ganglia ○ Ciliary ganglion (sphincter pupillae, ciliary muscle) via CN3 ○ Pterygopalatine ganglion (lacrimal gland, glands of nasal cavity) via CN7 ○ Submandibular ganglion (submandibular and sublingual glands via CN7 ○ Otic ganglion (parotid gland) via CN9 Rule of 4’s Four cranial nerves emerge above the pons Cerebrum ○ CN1 = telencephalon (embryonic cerebral cortex) ○ CN 2 = diencephalon (embryonic basal ganglia) Midbrain ○ CN3 = midbrain-pontine junction Palsy → Impaired adduction, supraduction and infraduction of the ipsilateral eye +/- dilated pupil ‘Down and out ‘ ○ CN4 = exits posteriorly from the midbrain Unable to look down when the eye is looking down towards the nose Rule of 4’s Four cranial nerves emerge from the pons CN5 = pons ○ Ipsilateral alteration of pain, temperature, light touch on the face, back as far as the anterior ⅔ of the scalp and sparing the jaw angle CN6 = pontine-medullary junction ○ Ipsilateral weakness of eye abduction (lateral rectus) CN7 = pontine-medullary junction ○ Ipsilateral facial weakness CN8 = pontine-medullary junction ○ Ipsilateral deafness ○ Nausea and vomiting Rule of 4’s Four cranial nerve emerge from the medulla Medulla oblongata ○ CN9 = posterior to the olive Ipsilateral loss of pharyngeal sensation ○ CN10 = posterior to the olive Ipsilateral palatal weakness ○ CN11 = posterior to the olive Ipsilateral sternocleidomastoid and trapezius weakness ○ CN12 = anterior to the olive Ipsilateral weakness of the tongue Medial and Lateral Medullary Syndrome Medial Medullary Syndrome = 4 deficits associated with 4 medial structures Motor pathways (corticospinal) - contralateral weakness of arm and leg Medial lemniscus (DCML) - contralateral loss of vibration and proprioception in arm and leg Medial longitudinal fasciculus - ipsilateral internuclear ophthalmoplegia Motor nuclei - ipsilateral loss of cranial nerve that is affected (3, 4, 6 or 12) ○ Motor nuclei of 3, 4, 6 and 12 are midline (all divisible into 12) Lateral Medullary Syndrome = 4 deficits associated 4 lateral structures Sympathetic - ipsilateral Horner’s syndrome, partial ptosis and miosis Spinothalamic - contralateral alteration of pain and temperature, affecting the arm and leg, rarely the trunk Spinocerebellar - ipsilateral ataxia of arm and leg Sensory nucleus for CN5 - ipsilateral alteration of pain and temperature on the face ○ 5th sensory nucleus = long vertical structure extending in the lateral aspect ○ May also involve 5/ 7th if pons lesion and 9/ 11th nerves if medulla Cerebellum Part of the hindbrain located posterior to: ○ 4th ventricle ○ Pons ○ Medulla Separated from the overlying cerebrum by the tentorium cerebelli Connected to the midbrain via the: ○ Superior cerebellar peduncle ○ Middle cerebellar peduncle ○ Inferior cerebellar peduncle Functions ○ Plays a significant role in motor control Does not initiate movement but contributes to coordination, precision and accurate timing Receives input from sensory systems and from other parts of the brain and integrates these inputs to fine-tune motor activity May also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses ○ Cerebellar damage produces disorders in fine movement, equilibrium, posture and motor learning  Organisation of the Cerebellum Dentate nucleus One of four pairs of deep cerebellar nuclei Largest and most lateral - located within the deep white matter of each cerebellar hemisphere Responsible for planning, initiation and control of voluntary movements ○ Dorsal region contains output channels involved in motor function, which is the movement of skeletal muscle, ○ Ventral region contains output channels involved in nonmotor function, such as conscious thought and visuospatial function. Anterior lobe = above the primary fissure Posterior lobe = below the primary fissure Cerebellum-vermis The cerebellum-vermis is located in the medial zone of the cerebellum Functionally, the vermis is associated with bodily posture and locomotion The vermis is included within the spinocerebellum and receives somatosensory input from the head and proximal body parts via the ascending spinal pathways Organisation of the Cerebellum Peduncles Superior - primary output from the cerebellum to the midbrain Middle - input from the contralateral cerebral cortex Inferior - ipsilateral proprioceptive information form the spinal cord Cerebellar tonsil The cerebellar tonsil is a rounded lobule on the undersurface of each cerebellar hemisphere, continuous medially with the uvular of the cerebellar vermis and superiorly by the flocculonodular lobe May herniate through the foramen magnum (tonsillar herniation/ coning) Flocculonodular lobe (vestibulocerebellum) Primary connections are with the vestibular nuclei, but also receives visual and other sensory input Participates mainly in balance and spatial obstruction Damage to this region causes disturbances of balance and gait Cerebellar Lesions Vestibulocerebellum lesions Spinocerebellum lesions Cerebrocerebellum lesions Balance Ataxia Loss of initiation, timing and Gait dysfunction Dyssynergia sequencing of movements Nystagmus Dysmetria (musical instruments Balance and stability Dysdiadochokinesia Loss of cognitive Refining ongoing functioning movements Ascending Tracts Ascending tracts are responsible for transmitting sensory information (somatosensory pathways) from the peripheral nerves to the cerebral cortex Can be divided into unconscious and conscious tracts ○ Conscious tracts Dorsal column-medial lemniscal pathway Anterolateral system ○ Unconscious tracts Spinocerebellar tracts  Dorsal Column Medial Lemnisacl Pathway Function Carries fine touch, vibration and proprioception Course 1st order neurons travel via the posterior (dorsal) column in the spinal cord ○ Signals from the upper limb travel within the cuneate fasciculus (lateral dorsal column) ○ Signals from the lower limb travel within the gracile fasciculus (medial dorsal column) These synapse with 2nd order neurons in the medulla oblongata 2nd order neurons decussate within the medulla oblongata 2nd order neurons travel within the medial lemniscus to reach the thalamus These synapse with 3rd order neurons in the thalamus 3rd order neurons transmit sensory signals from the ventral posterolateral nucleus through the internal capsule to the primary somatosensory cortex in the brain  Spinothalamic Tract Function Anterior spinothalamic tract - carries crude touch and pressure Lateral spinothalamic tract - carries pain and temperature Course 1st order neurons enter the spinal cord and ascend ipsilaterally 1 or 2 vertebral levels These synapse with 2nd order neurons in the dorsal horn (substantia gelatinosa) of the spinal cord These 2nd order neurons decussate immediately and form 2 distinct tracts at this point ○ Crude touch and pressure enter the anterior spinothalamic tract ○ Pain and temperature enter the lateral spinothalamic tract These travel superiorly and synapse with the 3rd order neurons in the thalamus 3rd order neurons transmit signals from the ventral posterolateral nucleus through the internal capsule to the primary somatosensory cortex in the brain Spinocerebellar Tract Function Unconscious proprioception Course Posterior spinocerebellar tract = proprioceptive information from the lower limb → ipsilateral cerebellum (entering the cerebellum via the inferior cerebellar peduncle) Anterior spinocerebellar tract = proprioceptive information from the lower limb → ipsilateral cerebellum ○ Double decussation of fibres ○ Fibres ascend to the midbrain however make a sharp turn caudally and enter the cerebellum via the superior cerebellar peduncle Rostral spinocerebellar tract = proprioceptive information from the upper limb → ipsilateral cerebellum Cuneocerebellar tract = proprioceptive information from the upper limb → ipsilateral cerebellum (through cuneate fasciculus) Descending Tracts The descending tracts are the pathways by which motor signals are sent from the brain to lower motor neurons Can be divided into pyramidal and extrapyramidal tracts ○ Pyramidal tracts - pass through medullary pyramids of the medulla oblongata Originate in the cerebral cortex and carry motor fibres to the spinal cord and brainstem Responsible for voluntary control of musculature of the body and face Corticospinal tract = musculature of the body Corticobulbar tract = musculature of the head and neck ○ Extrapyramidal tracts - do not pass through medullary pyramids Originate in the brainstem and carry motor fibres to the spinal cord Responsible for involuntary and autonomic control of all musculature (e.g. tone, balance, posture, locomotions) All upper motor neurons synapse with lower motor neurons Cell bodies are located in the cerebral cortex or brainstem with axons in the CNS Corticospinal Tract Function Motor supply to the musculature of the body Course Receives input from the ○ Primary motor cortex ○ Premotor cortex ○ Supplementary motor area ○ Somatosensory area (allows regulation of the activity of the ascending tracts) Neurons descend through the posterior limb of the internal capsule Pass through the crus cerebri of the midbrain → pons → medulla Divides into the lateral and anterior corticospinal tract at the most inferior part of the medulla ○ Lateral corticospinal tract Neurons decussate immediately and descend inferiorly through the lateral funiculus of the spinal cord (limbs) Synapse with lower motor neurons in the ventral horn at all segmental levels ○ Anterior corticospinal tract Neurons descend through the anterior funiculus of the spinal cord and decussate at the level of termination in the ventral horn of the cervical and upper thoracic segmental levels (trunk, neck and shoulder) Corticobulbar Tract Function Motor supply to the musculature of the head and neck Course Arises from the lateral aspect of the primary motor cortex and passes through the internal capsule to the brainstem These neurons terminate on the motor nuclei of the cranial nerves Innervates cranial nerves bilaterally (fibres from the left primary cortex innervate both right and left trochlear nerves) ○ Exception = CN7 and CN12 only receive unilateral innervation from the contralateral cortex of the brain For CN7, this only affects muscles below the eyes If there is an CN7 upper motor lesion on the LHS cortex, there is right lower facial drooping Extrapyramidal Tracts Tracts which originate in the brainstem rather than the cortex of the brain Function = involuntary and autonomic control of all musculature Vestibulospinal tract Controls balance and posture (flexors of the arm and extensors of the leg) (medial and lateral) Fibres do not decussate and hence provides ipsilateral innervation Reticulospinal tract Medial reticulospinal tract (locomotion and postural ○ Arises from the pons control) ○ Facilitates voluntary movement by increasing muscle tone Lateral reticulospinal tract ○ Arises from the medulla ○ Inhibits voluntary movement by decreasing muscle tone Fibres do not decussate and hence provides ipsilateral innervation Rubrospinal tract Originates from the red nucleus (midbrain) Fibres do decussate and hence provides contralateral innervation Involves in fine control of hand movements Tectospinal tract Originates from the superior colliculus (midbrain) Fibres do decussate and hence provides contralateral innervation ○ Fibres terminate at the cervical level Coordinates head movements in relation to visual stimuli - reflex head movement to light and sound Other Tracts (not important) Raphespinal tract ○ Most dorsal part of the lateral funiculus ○ Contains large amounts of serotonin Hypothalamospinal fibres ○ Most dorsal part of lateral funiculus ○ Arise from the hypothalamus and end among the preganglionic neurons in segments T1 to L2 segment S2 to S4 segment Lesions Brown-Sequard Syndrome Hemisection of the spinal cord resulting in ○ Ipsilateral loss of proprioception, vibration sensation and motor function ○ Contralateral loss of pain and temperature sensation Lesions Gracilis fasciculus lesion = affects ipsilateral lower limb vibration, fine touch and proprioception Cuneate fasciculus lesion = affects ipsilateral upper limb vibration, fine touch and proprioception Lateral corticospinal lesion = initial loss of motor reflexes but will return and be exaggerated due to loss of descending inhibition Anterior corticospinal lesion = loss of muscular control of trunk and neck muscles Vasculature of the Brain & Brainstem Circle of Willis The brain receives a blood supply from the internal carotid arteries and vertebral arteries which join at the inferior aspect of the brain to form the Circle of Willis The circle of Willis can be categorised and divided into anterior circulation and a posterior circulation. Each of these arteries are paired (1 on both side) Anterior circulation arises from internal carotid arteries Posterior circulation arises from vertebral arteries These circulations are interconnected by bilateral posterior communicating arteries If one part of the circulation is compromised, alternative circulation can be provided to prevent ischaemia to the brain Allows for compensation Internal Carotid Artery Course Originates at the bifurcation of the common carotid artery at the level of C4 Moves superiorly within the carotid sheath Enters the cranium through the carotid canal (opening in temporal bone) Passes anteriorly through the cavernous sinus Branches of the ICA: Ophthalmic artery - supplies orbital structures Posterior communicating artery (anastomotic connecting vessels to posterior cerebral arteries/ PCA) Anterior choroidal artery Anterior cerebral artery (ACA) ○ Connected by a single anterior communicating artery - most common artery to be asbent from Circle of Willis Terminates as the middle cerebral artery (MCA) - supplies lateral cerebrum Vertebral Artery Course Arises from the subclavian arteries, medial to the anterior scalene muscle Ascends through the transverse foramina of the cervical vertebrae beginning at C6 Enters the cranial cavity through the foramen magnum (big whole) Branches of the Vertebral Artery Meningeal branch - supplies the falx cerebri 1 anterior and 2 posterior spinal arteries - supply the spinal cord Posterior inferior cerebellar artery (PICA) - supplies the cerebellum (LEARN!!) These arteries then converge to form a single basilar artery - supplies midbrain and cerebellum Branches of the basilar artery: ○ Anterior inferior cerebellar artery ○ Pontine arteries - supply pons ○ Superior cerebellar artery ○ Terminates as the posterior cerebellar artery Circle of Willis The actual Circle of Willis is formed by paired constituents: Anterior cerebral artery (X2) Internal carotid arteries (X2) Posterior cerebral arteries (X2) These are joined together by the: Anterior communicating artery (X1) ○ Joins right and left ACA Posterior communicating arteries (X2) ○ Joins ICA to ipsilateral PCA Abnormalities of Circle of Willis Anatomical Variations: Aneurysms: Posterior circulation anomalies are Aneurysm = abnormal dilation of a more common than anterior vessel (normally by more than 50%) circulation anomalies Common in the brain are Beri ○ Commonly hypoplasia of the aneurysms - 1% of population posterior communicating artery Causes Anomalies decrease circulatory ○ Weakening of arterial walls: ○ Congenital absence of smooth muscle at normality - increased turbulence and arterial junctions arterial pressure These can occur in the brain - typically at branching points → rupture ○ Subarachnoid haemorrhage ○ Haemorrhagic stroke ○ Pressure on adjacent structures Vascular Territories Cerebral Vasculature Artery Supply Brain functions compromised during stoke Anterior cerebral artery Frontal lobe + anteromedial Logical thought, personality, cortex sensorimotor functions (especially legs) Medial aspect (lower limb) of primary motor and somatosensory cortices Middle cerebral artery Portion of frontal lobe, lateral Sensorimotor function (especially face, (most commonly occluded surface of temporal and parietal throat, hands and arms), speech in embolic stroke) lobes (aphasia) Lateral aspect (upper limb) of primary motor and somatosensory cortices Posterior cerebral artery Occipital and temporal lobes Hemianopia of the opposite visual field Stroke Definition = group of disorders involving sudden, focal interruption of cerebral blood flow that causes neurological deficit Aetiology Typically involves cellular cerebral infarction Ischemic (80%) stroke results from thromboembolism, but also hypoperfusion Haemorrhagic (20%) stroke results from vascular rupture (often secondary to hypertension or vascular malformations) Presentation LOC, headache, paraesthesia, anaesthesia, weakness, paralysis, visual/ sensory changes, aphasia, dysarthria, dysphagia Hx of CVD, IHD, metabolic syndrome, smoking, diabetes, sedentary Stroke RHS Stroke LHS Stroke Left-sided hemisensory loss/ Right sided hemisensory hemiparesis loss/ hemiparesis Homonymous hemianopia Homonymous hemianopia Quick, inquisitive behavioural Broca's/ Wernicke's aphasia style Slow, cautious behaviour Hemi-spatial neglect style Amnesia Amnesia  Stroke ACA Stroke Contralateral hemiparesis and hemianesthesia below the knee ○ Greater involvement of legs > arms and face → gait apraxia Bladder incontinence (precentral lobule of medal cortex) Poor decision making, rational thinking (involvement of lover lobe MCA Stroke Contralateral hemiparesis and hemianesthesia ○ Greater involvement of arms and face > legs Aphasia (if dominant hemisphere affected) ○ Broca's or Wernicke's aphasia (lateral cortex) Sensory neglect (if nondominant hemisphere is affected) temporal/ parietal visual tract → contralateral homonymous hemianopia PCA Stroke Total hemisensory loss ○ Involvement of the thalamus which all sensory pathways pass Homonymous hemianopia ○ Lesion to the primary visual cortex → loss of visual field/quadrantanopia ± loss of retinal central image Amnesia Lacunar Stroke Small infarcts of deep white matter mainly affecting the basal ganglia, thalamus and internal capsule Often caused by systemic hypertension → hemorrhagic strokes of small arteries ○ Choroidal and lenticulostriate arteries most affected Variable presentation ○ Contralateral pure motor loss ○ Contralateral pure sensory loss ○ Ataxic hemiparesis ○ Dysarthria and clumsy hand Stroke Cerebral stroke Stroke Investigations Non-contrast CT Brain ○ First test in order to determine if ischaemic vs hemorrhagic Ischaemic = no obvious changes Haemorrhagic = definite white pattern in meningeal segments CT Brain angiography (for ischaemic strokes) Management Acute intravenous thrombolysis - alteplase (tPA) ○ Direct plasminogen activator which converts plasminogen to plasmin which actively cleaves fibrin apart ○ Must be administered with 4.5 hours of symptom onset Endovascular thrombectomy Antiplatelet therapy Cerebellar Vasculature Supplied by 3 primary arteries: Superior cerebellar artery - branch of basilar artery Anterior inferior cerebellar artery - branch of basilar artery Posterior inferior cerebellar artery - branch of vertebral artery Brainstem Vasculature Midbrain Superior cerebellar arteries Posterior cerebral arteries ○ Posterior choroidal ○ Interpeduncular branches Posterior communicating arteries Pons Pontine and paramedian branches of the basilar artery Superior cerebellar arteries Brainstem Vasculature Medulla Oblongata Anterior spinal artery and paramedian branches of the vertebral artery - medial part of the medulla oblongata ○ Occlusion of anterior spinal artery → medial medullary syndrome Posterior inferior cerebellar artery - posterolateral part of the medulla where the main sensory tracts run and synapse ○ Occlusion of the vertebral artery or PICA → lateral medullary syndrome Anterior inferior cerebellar artery Brainstem (Superior to Inferior) Haemorrhages and Herniation Extradural haemorrhage Subdural haemorrhage Subarachnoid haemorrhage Arterial bleed It usually results from tears in Thunderclap headache Classical lentiform/ lemon shape – bridging veins that cross the Blood in the CSF limited by suture margins subdural space. Stellate sign (star sign) Often there is loss of consciousness Classic crescentic/ banana shape - SAH may occur as a result of a head following a head injury, a brief limited by dural attachments and so injury or spontaneously, usually from regaining of consciousness, and then the brain stretches a ruptured cerebral aneurysm loss of consciousness again. ○ Basilar artery rupture Damage of the middle meningeal ○ Vertebral artery rupture artery Herniation Definition: movement of the brain due to increased pressure within the skull Causes: brain oedema, haematoma, stroke, tumour, infection Supratentorial herniation Uncal = temporal lobe moving towards tentorium cerebelli squeezing midbrain Central = ascending or descending movement across the tentorium cerebelli Subfalcine = frontal lobe moves under the falx cerebri Transcalvarial = herniation through a fracture or surgical site Supratentorial herniation Upward or downward tonsillar cerebellar = movement of cerebellum. Downward movement through foramen magnum = coning → cardiorespiratory arrest → ded  Neurophysiology Kevin: [email protected] Movement and Balance Basics of Movement Movement requires: ○ Planning the movement ○ Initiation of the movement ○ Co-ordination of multiple muscles in space and time ○ Refinement of movements using sensory feedback ○ Optimisation of movements as they are repeated UMNs innervate LMNs, LMNs directly innervate muscle ○ LMNs are involved in all movements (both voluntary and reflexive) and trigger contraction via APs Cell bodies are located in the spinal cord and have three sources of input: Sensory input from muscle spindles, from spinal interneurons and from descending UMN This allows them to engage in reflexive movements ○ UMNs control voluntary/planned movements and DO NOT DIRECTLY innervate muscle Cell bodies are usually in the motor cortex and primarily descend in the lateral corticospinal tract Within the cerebellum and the basal ganglia, there are loops to control this function Motor Cortex The motor cortex, also termed M1, is a strip of cortex anterior to the central gyrus ○ Has a ‘coarse somatotopic organisation’ meaning certain areas generally innervate certain parts of the body (it is NOT perfect and very rarely is only one muscle moved, normally synergistic) This is the idea of the homunculus and there are three major regions Moving from lateral to medial, these are the face, arms and legs Adjacent muscle groups are targeted by adjacent regions of the cortex The surface area in the cortex is proportional to the level of fine muscular control Eg. hands have a large surface area Organisation of the Descending Pathways The main descending pathway is the lateral corticospinal tract (80-90% of neurons) ○ This pathway will decussate at the pyramids, meaning the left side of the brain innervates the right sided muscles ○ There is topographical organisation in both the white matter of the lateral corticospinal tract and the ventral horn In the lateral corticospinal tract, from lateral to medial the regions are as follows: Sacral, lumbar, thoracic and cervical (basically think inferiorly to superiorly in the body) In the ventral horns, extensors are found more dorsal (posterior) than flexors ○ There is also similar organisation of the ascending motor tracts Note the cervical portion is always closest to the grey matter and they are always in order Key Points of the Descending Pathways UMN vs LMN Lesions UMN Lesions: LMN Lesions: Symptoms are different in the short vs long-term Caused by trauma, ischemia or infection Immediate symptoms are from spinal shock: Due to complete loss of innervation and causes: ○ Flaccidity ○ Flaccid paralysis ○ Hypotonia (decreased spinal cord activity) ○ Paresis (weakness/incomplete paralysis) ○ Areflexia Impaired voluntary power ○ Much like a LMN lesion ○ Muscle atrophy Long term symptoms are: ○ Areflexia (loss of the efferent branch) ○ Loss of fine/fractionated movements but general movements return ○ Spasticity (hyperreflexia and hypertonia) ○ Babinski sign Signs of UMN Lesions Explained Hyperreflexia, Hypertonia and the Babinski Reflex Explained: ○ Hyperreflexia develops from a failure of the myotatic/stretch reflex Normally, the unexpected muscle stretch leads to reflexive contraction with reciprocal inhibition of the antagonist muscle from Ia neurons The antagonist muscle portion is under descending control from UMNs This can be deliberately used via the Jendrassik maneuver, decreasing the descending control and heightening the reflex This is also what happens due to injury to the UMNs causing inhibition of the reflexive response of the antagonist muscle ○ Leads to exaggerated reflexes and can cause clonus (rhythmic cycle of contraction and relaxation) ○ Hypertonia develops due to ongoing contractile activity in muscle Due to hyper-excitability/tonic stretch receptor input ○ Babinski sign is a pathological dorsiflexion and to fanning which is normal in infants Reflects damage to the motor neurons/corticospinal damage Regions of the Cerebral Cortex Area 4/Primary Motor Cortex/M1 ○ Volitional movements start here and outputs project down the corticospinal tract ○ They are only active when executing movements ○ Inputs from area 6 and somatosensory areas 1, 2 and 3 Most of the time written as 3, 1 and 2 by convention Area 6/Pre and Supplementary Motor Areas/PMA and SMA ○ PMA is responsible for sensory guided movements ○ SMA is responsible for planning of motor actions especially from memory (muscle memory) and acquiring new motor sequences (rehearsing) Has inputs from the PPC Some output down the corticospinal tract ○ Generally what happens is complex motor plans are made in area 6 and sent to area 4 and broken down into a different plan that can be sent down the LMNs ○ Lesions result in apraxia (inability to generate complex movements) Simple movements are ok however Regions of the Cerebral Cortex Part 2 Areas 5 and 7/Posterior Parietal Cortex/PPC ○ These are sensory motor integration areas using visual and proprioceptive information to guide motor plans in M1 ○ Area 5 receives somatosensory information from areas 1, 2, and 3 ○ Area 7 receives visual and proprioceptive information Connected with the premotor and prefrontal areas Lesions are complex; affects body image, perception of spatial relations and decision making Role of the Cerebellum The cerebellum helps refine movements but does not target LMNs ○ Involved in maintenance of balance and posture ○ Coordination of voluntary movements ○ Motor learning ○ Cognition There are three cerebellar functional areas: ○ Vestibulocerebellum ○ Spinocerebellum ○ Cerebrocerebellum Cerebellar outputs target the contralateral motor cortex ○ This means the cerebellum targets IPSILATERAL movements ○ This is because the cerebellar cortex projects to ipsilateral deep nuclei which projects to the contralateral brain stem nuclei and motor cortex The output axons from these will decussate at the pyramids and as such end up on the ipsilateral side Vestibulocerebellum Anatomical location: Symptoms: ○ Flocculonodular lobe ○ Difficulty maintaining balance/posture Function: ○ Inability to incorporate vestibular ○ Balance, gait and eye movements information ○ Difficulty controlling eye position during Inputs: head/body movements ○ Vestibular system ○ Head, neck and trunk ○ Superior colliculus ○ Visual cortex Spinocerebellum Anatomical location: Symptoms: ○ Vermis and the intermediate hemisphere ○ Ataxia: uncoordinated/inaccurate Function: movements ○ Control of ongoing limb movements This is speed dependent and Does this from proprioceptive movements are more disorganised information the faster you go ○ Dyssynergia: decompensation of synergic Inputs: multi-joint movements, eg. finger to nose ○ Ascending sensory information from the test spinal cord ○ Dysmetria: lack of coordination resulting ○ Contralateral motor cortex in overshoot or undershoot (past pointing) ○ Dysdiadochokinesia ○ Intention tremor Cerebrocerebellum Anatomical location: Symptoms: ○ Lateral hemispheres ○ Affected motor memory Function: Delays in movement initiation ○ Planning, modifying and learning Irregularities in timing movement movements components This is about trial and error learning ○ Affected cognitive function Spatial cognition Inputs: Affect (the impression of one’s mood ○ Contralateral cerebral cortex (both motor perceived by another person) and sensory)  General Principles of Cerebellum Pathology Aetiology: Presentation: Tumours: Infection: DANISH: ○ Hemangioblastoma ○ Abscess ○ Dysdiadochokinesia ○ Medulloblastoma Development: ○ Ataxia Vascular: ○ Arnold Chiari ○ Nystagmus ○ Haemorrhage malformation ○ Intention tremor ○ Infarction ○ Cerebral palsy ○ Slurred speech ○ Arteriovenous Inherited: ○ Heel to toe walking and malformation ○ Friedreich's ataxia hypotonia Toxic: ○ Ataxia telangiectasia Ipsilateral cerebellum is affected ○ Chronic alcohol abuse to the pathological side ○ Lead poisoning If bilateral, think drugs and toxins Basal Ganglia The basal ganglia forms a motor loop with the cortex and thalamus ○ The cortex sends signals to the basal ganglia (naturally inhibitory) which modulates the amount of movement via dopamine through the internal pathways ○ This is then sent to the thalamus which is naturally excitatory and sends it back to the cortex The basal ganglia has 2 roles: ○ Shifting between mental sets Mental sets are a body position, movement, complicated behaviour or a thought process ○ Reinforcement learning Within the basal ganglia there are three important sub-circuits: ○ Two main pathways are: Direct pathway Indirect pathway ○ Dopamine pathway ○ These are controlled by inhibitory (GABA) and excitatory (glutamate) neurotransmitters Direct Pathway of the Basal Ganglia This is a positive feedback loop and has a net facilitatory effect on the cortex ○ In words the pathway is as follows: The cortex sends an excitatory signal to the striatum, potentiating its inhibitory signal The increased inhibitory signal from the striatum, inhibits the inhibitory signal from the globus pallidus internus/substantia nigra reticular This reduces the naturally inhibitory effect on the VLo (ventrolateral nucleus pars Oralis in the thalamus) As a result the excitatory signal from the VLo is unimpaired A small increase in cortex function will thus self-propagate if not counter acted by the indirect pathway Indirect Pathway of the Basal Ganglia This competes with the direct pathway and overall has a suppressive effect on the cortex ○ In words, the pathway is as follows: Again, there is an excitatory signal from the cortex, increasing the striatums normal inhibitory response, this time affecting the globus pallidus externus This inhibits the GPe’s normal inhibitory effect on the STN (subthalamic nucleus), increasing it’s positive effect on the GPi/SNR In contract this strengthens the inhibitory effect on the VLo, decreasing the excitatory effect from the VLo on the cortex, thus having a net suppressive effect Role of Dopamine Dopamine is what controls whether it is the direct or indirect pathway that is taken ○ If dopamine is present, the direct pathway is selected and vice versa is dopamine is not present Pathways: ○ Direct: The GPi have D1 receptors which are excited by dopamine, thus dopamine will trigger this pathway to occur ○ Indirect: The GPe have D2 receptors are which inhibited by dopamine and thus dopamine will inhibit this pathway Dopamine comes from the pars reticulanum/substantia nigra compacta/SNc Damage to the basal ganglia results in over or under initiation of these movements ○ Hypokinetic disorders (eg. Parkinson’s disease) are from overactivity of the indirect pathway from a reduction in dopamine, leading to akinesia or bradykinesia ○ Hyperkinetic disorders (eg. Huntington’s disease) are from underactivity of the indirect pathway, leading to dyskinesia and hypotonia Parkinson’s Disease Definition: ○ Progressive neurodegenerative disorder characterised by resting tremor, rigidity, bradykinesia and postural instability, affecting 1% of those over 60 Aetiology: ○ Parkinson’s disease is idiopathic and is thought to be a combination of environmental and genetic factors Some gene mutations are associated with young-onset (21-40) or juvenile (