Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 1

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 2 A tour through the motor side of the human central nervous sytem - simple to more complex We will proceed from: - fundamental to supplementary - phylogenetically old to phylogenetically new

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 3 'Stimulus-response' design of the NS Stimulus Simple reflex Simple behaviour Cognition

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 4 1. Spinal reflexes - involuntary Are: - stereotyped - triggered by always the same stimulus - single (non-repetitive) events

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 5 1. Spinal reflexes Conclusion Simple reflexes are not enough to produce behaviours that are typical for animals, such as locomotor, consumatory, and copulative acts. More elaborate networks of neurones are needed in which movement-related activity is generated and maintained in the absence of a stimulus.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 6 3. Central pattern generators (CPGs) Examples: walking, running, chewing, scratching, swimming, respiration CPGs are: - stereotyped - repetitive - involuntary but can be controlled from other CNS structures - produced by neurones or network of neurones CPG

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 7 CPG and decerebrated animals Reflexive movements and movements produced by CPGs are driven by local neural circuits and do not require control from higher CNS centres. They are present even after the transection of neuraxis above their CPG. When an important part of the brainstem is spared, an animal can live without the head. Mike the rooster lived for 18 months.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 8 Mollusks: Ganglia contain CPGs Pedal ganglia

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 9 2. Central pattern generators Conclusion The CPGs are local networks that control a limited range of skeletal muscles. Some of them are triggered by a stimulus and then maintain their activity for a while, some are active all the time (e.g., breathing). Together with simple reflexes, the CPGs are sufficient to support life functions of primitive organisms or simple decerebrate vertebrates.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Extrapyramidal system Rubrospinal tract contralateral α and γ motoneurones Pontine reticulospinal tract ipsilateral γ motoneurones Tectospinal tract contralateral α and γ motoneurones Vestibulospinal tract ipsilateral α and γ motoneurones Olivospinal tract contralateral α and γ motoneurones Medullary reticulospinal tract bilateral α and γ motoneurones

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Extrapyramidal system Rubrospinal Reticulosp. Olivospinal Vestibulosp. Tectospinal

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 12 Red nucleus – rubrospinal tract Stimulates upper limb flexors Pontine reticular nucleus - medial reticulospinal tract Stimulates antigravity muscles Medullary reticular nucleus - lateral reticulospinal tract Inhibits axial extensor muscles Vestibular nuclei – vestibulosp. tr. Head and eye coordination, upright posture, balance, by stimulating antigravity muscles

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 13 Superior colliculus - tectospinal tract Reflexive head and eye movements as part of the orienting reaction Inferior olivary nucleus - olivospinal tract Accuracty of movement, reflexes to proprioceptor stimulation

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 14 3b. Cranial nerves – motor part V Trigeminal (mandib.) - trigeminal motor nucl. Muscles of mastication IV Trochlear – contralateral trochlear nucl. Superior oblique muscle III Oculomotor – oculomotor nucleus Levator palpebrae superioris muscle, superior, medial & inferior recti muscles VI Abducens – abducens nucleus Lateral rectus muscle

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 15 3b. Cranial nerves – motor part X Vagus – nucleus ambiguus Muscles of the larynx and pharynx IX Glossopharyngeal – nucleus ambiguus Stylopharyngeus muscle VII Facial – facial nerve nucleus Muscles of the face XI Abducens – spinal accessory nucleus Sternocleidomastoid and trapezius muscle XII Hypoglossal – hypoglossal nucleus Muscles of the tongue

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Extrapyramidal system Conclusion Spinal motor tracts belonging to the so-called extrapyramidal system control most muscles, mainly to maintain optimum muscle tone, posture, balance, and orienting towards stimuli. Eight cranial nerves have a motor component that controls mainly the muscles of the eyes, face, and mouth.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Extrapyramidal system The rubrospinal tract, which is phylogenetically younger than other extrapyramidal pathways, plays a greater role in animals than in humans. In humans, the motor control via the rubrospinal tract is present in newborns. As the motor cortex matures (= reduction of layer IV), the emphasis shifts from the nucleus ruber to the motor cortex. Conclusion (.. continued)

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 18 LampreyFrogTroutSharkCrocodile PigeonRabbitDog 4. Cerebellum

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Cerebellum (size ~ movement complexity) Elephant

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Cerebellum Click on the picture to start the video

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Cerebellum Neocerebellum Paleocerebellum Archicerebellum Vestibulocerebellum (flocculonodular lobe) Cerebrocerebellum (lateral part) Spinocerebellum (medial part) Anatomical division ‘Functional’ division

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Cerebellum Electrical stimulation does not cause muscle contraction People born without the cerebellum do not need support Monkeys with the cerebellum removed can move well In humans: - floccular destruction affects balance and eye movements - destruction of the vermis leads to gait ataxia (drunken sailor) - destruction of the hemispheres leads to upper limb ataxia In general, the cerebellar dysfunction affects balance, posture, eye movements, and movements controlled by will Facts:

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Cerebellum - Ataxia Click on the picture to start the video

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 24 'Stimulus-response' – NS design Vestibular Proprioceptive Vestibular Proprioceptive Simple reflexes Cerebellum Cognition Movements

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Cerebellum Conclusion The cerebellum serves as a processing unit between the vestibular and proprioceptive inputs and motor output paths. It task is to use available sensory information to produce fine modifications of efferent motor signals. This helps maintaining proper posture, balance, muscle tone, and timing of muscle contraction.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Corpus striatum Corpus striatum = nucleus caudatus + putamen + globus pallidus

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Basal ganglia Motor cortex Putamen Globus pallidus - external segm. Globus pallidus - internal segm. Thalamic ventrolat. nucleus (VL) Subthalamic nucleus (STN) Substancia nigra

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Basal ganglia - diseases

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 29 Jung and Hassler: “Bilateral destruction of the pallidum does not produce any motor symptoms.” 5. Corpus striatum MacLean: “More than 150 years of investigation has failed to reveal specific function of the striatal complex.” Facts: Large lesions in the striatal complex result in no obvious motor disability. Bilateral lesions of the caudate nucleus may produce behavioural persistence and hyperactivity. Electrical stimulation has no motor effects. It can cause blocking of voluntary behaviours. Laughing and crying has also been described.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Corpus striatum Cooper: “The role of the thalamus in motor activity likewise appears difficult to define at this time. One may interrupt pathways from the globus pallidus, red nucleus, and the cerebellum to the thalamus as well as the thalamo-cortical and cortico-thalamic circuits without causing either motor weakness or faulty coordination upon the patient.” Facts: MacLean: “The evidence indicates that the striatal complex is not solely a part of the motor apparatus under the control of the motor cortex.”

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Basal ganglia Parent et al.: “The major axonal branches of the GPi are those that descend within the brainstem, whereas the Gpi innervation of the thalamus is made up of fine collaterals that detached from these thick descending fibers. The GPi descending fibers arborise principally in the PPN [pedunculo-pontine nucleus].” GPi is activated after the activation of the primary motor cortex. The motor cortex – corpus striatum – thalamus circuit does not represent an array of mutually segregated loops through which motor programs reverberate unchanged, as previously thought.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Basal ganglia Strong hypotheses: BG lesions specifically block the influence of task incentives on movement vigor. BG are important for learning new motor skills. The limbic input provides for reinforcement signals that determine what is or what is not to be learnt. Long-term memories are stored in motor cortices.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Corpus striatum Conclusion The basal ganglia can be thought of having a similar function as the hippocampus in relation to forming long-term memories in the cerebral cortex. Both structures serve as processors that store information (sensory-derived in the case of the Hipp and motor-derived in the case of BG) in the neocortex based on its importance or emotional impact. This latter aspect is provided to them by the limbic system.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Pyramidal system Pyramidal tract

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Pyramidal tract Pyramidal tract starts in layer V of MI, PM, SMA areas of the motor cortex (see next slide for abbreviations). It controls most muscles, mainly the distal ones.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Motor cortex Primary motor cortex (MI) Supplemetary motor area (SMA) Premotor cortex (PM) PM SMA MI Motor “homunculus”

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Motor cortex (fMRI)

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Motor cortex Facts: MI – Is active during movement. It activates individual muscle groups. PM – Is active before movement. The movement does not have to happen. It is important for the control of learnt automatic movements under the influence of sensory feedback. Speaking, eye control, and writing are some examples. SMA - Is active before movement. The movement does not have to happen. It is active during planning of movement.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Motor cortex (localisation by stimulation) Click on the picture to start the video

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page Motor cortex Conclusion The primary motor cortex (MI) has evolved from the somatosensory cortex. It shares the same function with other (sensory) neocortical areas: It serves as a substrate for conscious awareness and as a store of long-term memory traces. The MI stores “motor primitives” (that correspond to individual muscle groups), PM and SMA store more complex patterns of movement and behaviour.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 41 Summary of connections (simplified) motor cortex thalamus cerebellum corpus striatum nucleus ruber motor nuclei in the pons and medulla oblongata labyrinth and proprioceptors spinal cord pyramidal tract Phylogenetically younger connections are light green. The projections from from the corpus striatum and cerebellum to the thalamo-cortical system allow for awareness of the movement and also its storage in declarative memory.

Department of Physiology, 2nd Medical School, Charles University Copyright © 2013 Luděk Nerad Motor control Neurophysiology page 42 Final summary 1. Even the simplest vertebrates can't do with simple reflexes and central pattern generators, despite the fact that they can survive with them. 2. Even the simplest vertebrates are able to fine-tune movement coordination and move in the gravitational field (with the help of the cerebellum). 3. Even the simplest vertebrates must possess patterns of species-specific behaviours. A major role here is played by the corpus striatum. 4. In man and higher vertebrates, a system has evolved that consciously processes information from long-distance sensory modalities – vision and hearing. It has affected a system that controls behaviour - basal ganglia, and the motor cortex emerged along with its connections with the cerebellum and striatum..