Learning Objectives

Up to this point, we have focused on structures and circuits that enable voluntary movement and which, when damaged, result in some degree of weakness even to the level of paralysis if the damage is severe. We turn our focus now to other structures in the motor system that enhance voluntary movements, making them more smooth, coordinated, efficient. When these structures are damaged, there is a degradation in the quality of movement, rather than weakness.

In the diagrams below, trace the loops of connection involving the cerebellum and basal ganglia. Notice that while we think of these as being “motor” structures, neither the cerebellum nor basal ganglia have direct connections to motor neurons. Their influence on motor function is mediated through their effect on the cortex (and thus the corticospinal/corticobulbar tracts) and on the reticular and vestibular nuclei (and thus the reticulospinal and vestibulospinal tracts respectively).

Basal Ganglia

The basal ganglia include structures in the core of the cerebral hemispheres, the diencephalon, and the midbrain. The caudate and putamen are often referred to as the striatum because of their common embryological derivation and their role as input nuclei for the basal ganglia. The globus pallidus and putamen are referred to as the lentiform nucleus in the context of anatomical location.

The substantia nigra is in the midbrain and the subthalamic nucleus is a nucleus in the diencephalon.

Here are 3 movies that show 3D visualizations of the caudate, putamen and globus pallidus, reconstructed from MRI scans. You might also like to review the more detailed narrated videos in Chapter 2 by Dr. John Sundsten.

This one shows the caudate and putamen. Notice the gap between them? This is where the fibers of the internal capsule pass to and from the cortex and thalamus. The yellow area appearing to connect the caudate and putamen at their most anterior-ventral point is the nucleus accumbens, a nucleus important in the reward pathway and in substance use disorders, but beyond the scope of this course.

This video shows the striatum in relationship to the lateral ventricle. Recall that the 3rd ventricle is surrounded by the thalamus and hypothalamus which both are medial to the basal ganglia.

This video shows a peeling away of the right frontal lobe to demonstrate how the globus pallidus (gray) nestles “inside” the putamen, and is smaller than it. The yellow fiber bundle is the anterior commissure.

Here are some images of dissections showing basal ganglia components in the forebrain.

In the following use the slider to test yourselves on what the colored arrows indicate to review the appearance of the large forebrain basal ganglia components in sections.

Substantia nigra and subthalamic nucleus.

Basal ganglia cortical loops and pathways

The basal ganglia are involved in multiple parallel circuit loops involving subsets of cells in cortex, basal ganglia, and thalamus. These circuits regulate many aspects of behavior including voluntary movement, eye movement, motivation, emotional and cognitive behavior. The loops all follow the basic pattern of connection that is

cortex ⇒basal ganglia⇒thalamus⇒cortex

The image below shows 3 of these loops. It is for your interest only. You need to know that such circuits exist, but you need only know the details for the circuit involved in voluntary motor activity as described in the next section.

Direct and indirect pathways in the motor loop

Two circuits through the basal ganglia are recognized as being essential for optimal motor control. Activity in these circuits has the net effect of selecting between competing options for movement or behavior, and inhibiting undesired movement or behavior. The direct pathway has the overall effect of facilitating activity in the thalamus and subsequently the cortex, while the indirect pathway inhibits movement by increasing the level of inhibition of the thalamus by the globus pallidus internus, and thus reducing activity in the cortex. As mentioned earlier, dopamine from the SNc acts through different dopamine receptors in the direct and indirect pathway, with the overall effect of facilitating movement by “boosting” activity in the direct pathway and “damping down” activity in the indirect pathway.

Basal ganglia subcortical pathways

Pathways descending from the basal ganglia to the midbrain locomotor area and especially the pedunculopontine nucleus, influence postural and limb girdle muscles via the vestibulospinal and reticulospinal tracts. Dysfunction in this pathway are evident in the characteristic stooped posture of people with Parkinson disease and their difficulties with gait. The image below contrasts the cortical and subcortical outputs from the basal ganglia and their downstream effects.

Basal Ganglia Disorders

Three important disorders involving the basal ganglia have obvious histopathological correlates (review lecture material for details on 1 and 2):

1. Parkinson disease associated with loss of dopamine and decreased staining of the SNc
2. Huntington disease associated with marked degeneration of the caudate (leading to abnormally wide anterior horn and body of the lateral ventricle) and putamen.
3. Hemiballismus (a movement disorder characterized by wild flailing movement of limbs) is associated with damage to the subthalamic nucleus.

The images below compare sections from pathological specimens (top images) vs normal specimens (bottom images) through the midbrain (left) and forebrain (right).

Arrows indicate regions of interest: A. SNc is diminished in Parkinson disease and B. caudate shows marked reduction and concomitant increase in lateral ventricle profile in late stage Huntington disease.

Cerebellum

The cerebellum accounts for about 12% of the mass of the brain, and contains an astounding 69 billion neurons (by comparison, the cerebral cortex comprises only 16 billion neurons). Despite this internal complexity, an interesting but important concept is that motor commands do not originate in the cerebellum – for instance even severe damage to the cerebellum does not leave patients paralyzed. Rather it takes in wide spread motor signals, additional cortical input including auditory and somatosensory inputs, vestibular and proprioceptive inputs, and projects to motor cortex and to other centers on the brainstem that help to regulate posture and movement.

The cerebellum

• makes movements fast, accurate, and smooth, serving to coordinate movements that involve simultaneous action at more than one joint or muscle group,
• regulates muscles involved in balance in order to maintain equilibrium and posture
• detects and predicts “motor errors” – the difference between intended movement and that actually performed, both “real-time” and long-term (a type of motor learning).
• plays a role in some cognitive function such as attention related behaviors and language (these roles are not well understood)

Gross anatomy of the cerebellum

There are several parts of the cerebellum to know. Study these images and try the  exercise to identify them.

The highly infolded cerebellar cortex (a folium is the equivalent of a gyrus in the cortex) is the main processing machinery of the cerebellum, and the Purkinje cells there can be thought of as conveying the result of that processing to the deep cerebellar nuclei, whose axons then leave the cerebellum to regulate the sources of tracts that influence LMNs. The only visible deep cerebellar nucleus is the dentate nucleus. It receives input from the overlying cerebellar cortex (ie of the lateral hemispheres) and projects to the contralateral red nucleus (to regulate rubrospinal tract activity) and to the contralateral thalamus which in turn projects to the cortex to regulate activity in the cortex (to regulate the corticospinal tract).

The fastigial nucleus is predominantly involved in eye movement, balance and posture; it send outputs to the vestibular and reticular nuclei to regulate the descending tracts from them. The interposed nuclei send some output rostrally with the dentate output and some caudally with the fastigial output.

The image below shows two views of the dentate nucleus–it appears like a gray squiggle or smudge in the deep white matter of the cerebellum. In an optimal cut it is easy to imagine the axons exiting the dentate nucleus to form the superior cerebellar peduncle. Notice how the SCP lies medial to the MCP and forms the walls of the upper part of the 4th ventricle as it narrows towards the cerebral aqueduct.

Cerebellar peduncles

The cerebellum is connected to the brainstem by axons passing into the cerebellum from various sources and axons from the deep cerebellar nuclei conveying output from the cerebellum.

The middle cerebellar peduncle is the only one that is visible without dissection of overlying cerebellar cortex. The superior cerebellar peduncle is rostral to the middle cerebellar peduncle (on the “midbrain side”) and the inferior cerebellar peduncle is caudal (on the “medulla side” of the middle cerebellar peduncle.)

Inputs to cerebellum

Inputs to the cerebellum can be classified by their termination “zone” in the cerebellum, by the morphology of their axons or by their origin (see image below). Each classification scheme has its benefits and drawbacks.

Vestibular input terminates in the vestibulocerebellum (flocculonodular lobe and vermis), input from the spinal cord in the spinocerebellum (anterior lobe and paravermal region) and input that originated in the cortex and is relayed into the cerebellum via the pontine nuclei and middle cerebellar peduncle terminates in the cerebrocerebellum (posterior lobe, lateral hemispheres of cerebellum).

Regardless of the origin of the inputs to the cerebellum, at a microscopic level, only two patterns of axonal termination exist based on their morphology:

• axons of inferior olivary nucleus cells form the climbing fibers, which dominate the dendritic tree of one or at most a few Purkinje cells (this is a unique instance in CNS connectivity)
• axons from all other sources form the so-called mossy fibers which terminate on the granule cells, Granule cells then relay that input to Purkinje via a unique arrangement of axons: each granule cell axon splits into 2 parallel fibers which run transversely, and supply a few synapses to vast numbers of Purkinje cells within a folium.

A classification by origin is helpful from a neuroanatomical perspective. This approach is summarized below.

Practice exercise:

Cerebellar outputs

The most significant output from the cerebellum is via the superior cerebellar peduncle and it crosses the midline to reach the contralateral red nucleus and thalamus (which then relays to cortex). This output is crucial for helping make voluntary movement smooth and coordinated by regulating activity in the corticospinal and rubrospinal tracts.

Other output from the cerebellum (some via the inferior cerebellar peduncle) regulates activity in the vestibulospinal and reticulospinal tracts, thus enabling the cerebellum to influence balance and posture.

You will note that pathways that interconnect the cortex and cerebellum involve crossing the midline. This makes sense because one side of the cerebellum regulates the same side of the body, while one side of cortex regulates the opposite side. For example to move the right side of the body smoothly and efficiently,  the left cortex must communicate with the right cerebellum and vice versa.

Summary of cerebellum function

A functional view of the cerebellum connections is presented below. Damage to the cerebellum can result in ataxia (lack of coordination), dysdiadochokinesia (impaired rapid, alternating movement), and problems with balance and posture. One overarching summary for cerebellar damage is that it creates errors in the rate, range, direction or force of voluntary movements.

Structures to Identify