Motor Modulation BG and Cerebellum - Part 2 Cerebellum Student (1) PDF

Motor Modulation: the Basal Ganglia and Cerebellum Part 2 – Cerebellum Neuroanatomy Dr. Kathleen Keefe [email protected] Disclosure I currently have no relationships of any kind with any company whose products or services in any way relate to the practice of medicine, medical education or...

Motor Modulation: the Basal Ganglia and Cerebellum Part 2 – Cerebellum Neuroanatomy Dr. Kathleen Keefe [email protected] Disclosure I currently have no relationships of any kind with any company whose products or services in any way relate to the practice of medicine, medical education or research Learning Objectives (Cerebellum) Identify lobes, fissures and deep nuclei of the cerebellum Describe the functional subdivisions of the cerebellum, including their anatomical territory, major inputs and outputs and the functions they are associated with Identify the cerebellar peduncles and describe the axons that run through them Describe the two types of incoming fibers to the cerebellar cortex, including where they originate Describe the two major cell types of the cerebellar cortex and how they interact Compare and contrast the symptoms of midline versus lateral cerebellar dysfunction Functions of the Cerebellum Coordination and balance: ○ Coordinates timing between different muscle groups to produce fluid movement Loss of coordination will produce ataxia ○ Ongoing adjustments to posture and balance, based on sensory feedback Influences UMNs of medial descending pathways to compensate for shifts in body position or changes in load on muscles Loss of this functionality leads to gait instability Vocab: Ataxia Disordered contractions of agonist and antagonist muscles and lack of normal coordination between movements at different joints. Irregular movements can include overshooting, overcorrecting, abnormal timing and abnormal trajectories Functions of the Cerebellum Error correction and motor learning: ○ Correcting or avoiding movement errors Feedback loops detect the difference between an intended movement (motor plan) and the actual movement (proprioceptive feedback), and reduces that difference Feed-forward loops predict and prevent errors ○ Motor learning – adapts motor programs to make future movements more accurate Feed-forward systems help with navigation by calculating trajectories of ourselves and the people around us Cerebellar Input During Movement Phases Motor commands are not initiated in the cerebellum; rather, the cerebellum modifies commands initiated in the motor cortices to make movements more accurate Cerebellar circuits are active either before a movement happens (planning), or while movement is ongoing (execution) ○ Motor learning and error prediction tweak motor programs to make them more efficient in the ‘planning movement’ stage ○ Error correction of ongoing movement happens in the ‘executing movement’ phase Case – Difficulty Walking A 76-year-old man with a history of smoking developed progressive difficulty walking over the course of 1 month. He noticed that when he stood up, he felt “woozy” and described his gait as feeling like he was drunk, saying “my legs go one way, and I go the other.” Exam was unremarkable except for a wide-based, unsteady gait, especially with tandem walking. There was no ataxia on finger-to- nose or heel-to-shin testing, and rapid alternating movements were normal. VOR is normal. There was no history of alcohol intake. Based on the case above, where is the lesion? Cerebellum – ‘little brain’ anterior A major structure in the CNS _____ to the brainstem and _____ to the occipital lobe/posterior portion of temporal lobe (fill in anatomical directions) Lateral view Posterior view Inferior view Cerebellar Hemispheres, Lobes and Fissures The cerebellum has two hemispheres laterally, connected medially by the vermis (purple arrow) You can also divide the cerebellum into 3 lobes, separated by 2 fissures: ○ Anterior, posterior and flocculonodular lobes ○ Primary and posterolateral fissures anterior lobe primary fissure primary fissure anterior lobe posterior lobe flocculonodular lobe* posterolateral fissure Posterior view Sagittal view Anterior View of the Cerebellum This view is as if looking posteriorly into the 4th ventricle with the brainstem dissected away The flocculonodular lobe consists of the nodulus and both flocculi together SCP White matter tracts such as the middle MCP (MCP) and superior (SCP) cerebellar peduncles can also be seen here Anterior view of the cerebellum Cerebellar Gray Matter Cerebellar gray matter is located in two distinct areas: 1. On the external surface (cerebellar cortex) arranged in long parallel folds called folia folia Diagram of a transverse section Posterior view Cerebellar Gray Matter Cerebellar gray matter is located in two distinct areas: 2. As nuclei deep within the white matter. There are 4 distinct nuclei. From most lateral to most medial, they are: Dentate Emboliform Known collectively as Ver Globose ‘interposed nuclei’ Fastigial 4th ventricle pons Vermis; dentate nucleus; interposed nuclei; fastigial nucleus Cerebellar White Matter White matter is located medially. Axons of incoming and outgoing fiber tracts make up the cerebellar peduncles. There are three: ○ Inferior (ICP) – incoming and outgoing fibers SCP ○ Middle (MCP) – only incoming fibers ○ Superior (SCP) – incoming and outgoing fibers MCP 4th ICP anterior pons deep nuclei MCP posterior view of brainstem, cerebellum dissected away cerebellar sagittal White matter transverse posterior cortex Cerebellar Blood Supply Three main arteries feed the cerebellum: ○ Superior cerebellar artery (SCA) – branches from rostral basilar artery. Supplies: Superior portion of cerebellum Deep cerebellar nuclei Superior cerebellar peduncle ○ Anterior inferior cerebellar artery (AICA) – branches from caudal basilar artery. Supplies: Anterior strip of cerebellum, including superior vermis Middle cerebellar peduncle ○ Posterior inferior cerebellar artery (PICA) – branches from vertebral artery. Supplies: Inferior cerebellum, including the nodulus Cerebellar Blood Supply Anterior view Nodulus Flocculi Posterior view Functional Subdivisions Certain anatomical territory in the cerebellum relates to specific functions: ○ Spinocerebellum – vermis and paravermis (immediately adjacent to vermis), including majority of anterior lobe ○ Cerebrocerebellum – lateral hemispheres (esp. posterior lobe) ○ Vestibulocerebellum – flocculonodular lobe Deep cerebellar nuclei are associated with functional Paravermis subdivisions, as they receive input from adjacent structures in the cerebellar cortex: ○ Dentate nucleus relates to the cerebrocerebellum ○ Interposed nuclei relate to the spinocerebellum ○ Fastigial nucleus relates to spinocerebellum or vestibulocerebellum Deep cerebellar nuclei are output structures of the cerebellum Functional Subdivisions: Spinocerebellum Functions in error correction: ○ Detects difference between motor plan and actual movement, and reduces that difference Receives projections from: ○ Proprioceptors (muscle spindles/golgi tendon organs) ○ Inferior olive (IO) Paravermis Receives extensive inputs (cerebral cortex, red nucleus, brainstem nuclei, spinal cord) Compares motor plan to sensory input, then sends integrated output to cerebellar cortex ICP IO Functional Subdivisions: Spinocerebellum Cortical neurons of the spinocerebellum synapse with the DCN, which will then output to: ○ UMNs of medial motor tracts (vestibular nuclei and reticular formation) Homunculi ○ UMNs of lateral motor tracts (CST) via VL of the thalamus The spinocerebellum has a fractured somatotopic map: ○ Vermis coordinates movements of the central body ○ Paravermis coordinates movements of distal muscles Midline Cerebellar Damage Cerebellar lesions restricted to the medial cerebellum (vermis and/or fastigial nucleus) have bilateral effects: ○ Loss of coordination of proximal muscles - affecting balance, posture and gait Truncal ataxia Wide, unsteady gait Lateral/Intermediate Damage Lesions in the intermediate zone can involve paravermis and interposed nuclei (spinocerebellum), and/or medial regions of the lateral hemisphere and dentate nucleus (cerebrocerebellum) Manifests as movement deficits in ipsilateral extremities: ○ Loss of coordination – moving joints separately instead of smoothly as one unit (appendicular ataxia) ○ Inaccuracy in range and direction of movement (dysmetria) Hand-to-nose or heel-to-shin testing ○ Trouble with patterned movement (dysdiadochokinesia) Dysmetria Dysdiadochokinesia Functional Subdivisions: Vestibulocerebellum Functions: ○ Corrections to stability and balance, both continuous and anticipatory ○ Contributes to vestibular ocular reflex and smooth pursuit eye movement Receives projections from: ○ Vestibular nuclei and vestibular ganglia ○ Inferior olivary nucleus Outputs directly to: ○ Vestibular nuclei (influencing vestibulospinals and eye movements) ○ Reticular formation (influencing reticulospinals) ○ Bypasses DCN Flocculonodular (FN) lobe syndrome: Damage to the FN lobe (common in children with medulloblastoma) can cause: Truncal ataxia Nystagmus Functional Subdivisions: Cerebrocerebellum Functions: ○ Motor learning – adapts motor programs to make future movements more accurate, especially skilled movements of distal extremities ○ Calculates movement trajectories Receives projections from: ○ Neurons in the base of the pons (pontine nuclei) Axons cross the midline and enter the cerebellum via the middle cerebellar peduncle ○ Inferior olivary nucleus Outputs to: ○ UMNs of lateral movement pathways via VL of thalamus  Self study Summary of Incoming Circuitry Afferent fibers enter the cerebellum from: ○ MCP: Pontine nuclei neurons ○ ICP: Vestibular nuclei neurons Inferior olivary neurons ○ SCP or ICP: Spinal cord neurons Case – Difficulty Walking A 76-year-old man with a history of smoking developed progressive difficulty walking over the course of 1 month. He noticed that when he stood up, he felt “woozy” and described his gait as feeling like he was drunk, saying “my legs go one way, and I go the other.” Exam was unremarkable except for a wide-based, unsteady gait, especially with tandem walking. There was no ataxia on finger-to- nose or heel-to-shin testing, and rapid alternating movements were normal. VOR is normal. There was no history of alcohol intake. Based on the case above, where is the lesion? How Does the Cerebellum Error Correct? Incoming fibers synapse in two places: ○ On neurons of the deep cerebellar nuclei PCs (DCN) neurons, which are the major outputs of the cerebellum. This provides excitatory input to stimulate these neurons to fire, sending the error correction signal out to CNS structures (deep excitatory loop) ○ On neurons called Purkinje cells (PC) in the cerebellar cortex DCN Purkinje cells provide modulatory inhibition to the DCN to adjust the outgoing signal (cortical inhibitory loop) Cells and Fibers of the Cerebellar Cortex The cerebellar cortex has 3 layers in which cells and fibers interact Incoming fibers called ‘mossy fibers’ originate from the spinal cord, and pontine and vestibular nuclei Cerebellar cortex ○ Mossy fibers synapse either on DCN or on granule cells of the cortex ○ Granule cells send axons towards Purkinje cell dendrites. The axons bifurcate into a T shape called a parallel fiber Purkinje cells have enormous dendritic arbors in a narrow plane, allowing cells to synapse with 100,000-200,000 parallel fibers Cerebellar cortex showing 3 layers Cells and Fibers of the Cerebellar Cortex Axons from the inferior olive enter the cerebellum as ‘climbing fibers’ ○ This is the integrated comparator signal Climbing fibers that make excitatory synapses with Purkinje cells wrap around their dendrites ○ Especially active when an unexpected event occurs, i.e. a divergence from the plan Climbing fibers modify the efficacy of the parallel fiber-Purkinje cell connection ○ The output of Purkinje cells onto DCN is inhibitory – it modifies the signal based on the evolving plan DCN provide the final output of the cerebellum onto CNS structures “The cerebellum acts like an air traffic controller who gathers an unbelievable amount of information, including (for example) the position of your hand, arm, and nose, the speed of movements, and the effects of potential obstacles, so that your finger can achieve a "soft landing" on the tip of your nose” Cerebellar Output Cerebellar cortex projects to DCN, and DCN project to other parts of the brain ○ Exception - vestibulocerebellar efferents project directly to vestibular nuclei All pathways leaving the cerebellum project to UMNs. Many travel through the superior cerebellar peduncle ○ Most axons of DCN cross the midline to synapse on contralateral structures (i.e. VL of thalamus) Most Lesions are Ipsilaterally Affecting Considering most cerebellar output crosses the midline, you might expect lesions to cause contralateral symptoms However, damage to the intermediate and lateral cerebellum usually produces symptoms on the ipsilateral side of the body. This is because: ○ Though output from deep cerebellar nuclei (4) synapses on contralateral structures (5). This output affects motor tracts which often cross the midline themselves (6) before they interact with LMNs (7) The exception is damage to the vermis, which is bilaterally affecting Movement Example – Throwing a Disc What areas are involved in the action of throwing a disc in an ultimate frisbee game? Planning Phase Supplementary motor area Mental rehearsal of throw (internal cue) Many of these are innervated by areas Coordinate muscle groups on both sides of processing sensory info the body Visual cortex – where teammates and defenders are located, are teammates Premotor cortex open and ready to receive throw? Plan release of throw based on external ‘What’ pathway (traveling through cues such as when receiver is ready superior parietal lobule) – recognize disc Basal nuclei in your hand, understand force needed Initiate the motor program that will: to grip and throw Start arm and wrist flexed with a firm grip Somatosensory cortex – understand Extend the arm and wrist and release windspeed Repress unwanted motor programs Parietal lobe – proprioceptive info Reticulospinal tract Contract leg muscles due to the anticipated instability that will happen when throw occurs Cerebellum Coordinate muscle groups to create fluid throw Anticipate errors based on previous throws Movement Example – Throwing a Disc What areas are involved in the action of throwing a disc in an ultimate frisbee game? Initiation Phase Primary motor cortex (UMNs) Stimulate CST neurons that contact LMNs/LCNs Initiation phase that contract the arm, wrist and hand muscles Execution Phase Execution phase LMNs Stimulate muscles to contract Cerebellum Correct errors during movement execution based on comparison of movement to motor plan Help maintain balance Vestibular neurons Maintain balance based on head movements Resources Basic Clinical Neuroscience – Chapter 9 Neuroanatomy through Clinical Cases – chapter 15 3d model: https://sketchfab.com/3d-models/cerebellum-3a4e017a202a4928b666371d07 5d0e21 Purkinje cell/parallel fiber animation: https://nba.uth.tmc.edu/neuroscience/m/s3/chapter05.html#:~:text=Motor%20l earning.,Cognitive%20functions Ataxic gait video: https://www.youtube.com/watch?v=lrerPzLtnY8 Dysmetria video: https://www.youtube.com/watch?v=jnQcKAYNuyk Dysdiadochokinesia video: https://www.youtube.com/watch?v=gNZFSUdL_uc