A number of biochemical aspects of cerebellar function are of interest. Four of the five cell types of the cerebellar cortex (Purkinje, stellate, basket, Golgi) are inhibitory; the granule cells are an exception and are excitatory. Afferent fibers to the cerebellum are of three types, two of which have been mentioned above: (1) mossy fibers, which are the main afferent input to the cerebellum, utilize aspartate. (2) Climbing fibers, which are the axons of cells in the inferior olivary nucleus and project to the Purkinje cells of the opposite cerebellar hemisphere. The neurotransmitter of the climbing fibers is probably glutamate, which acts on amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. (3) Aminergic fibers, which project through the superior cerebellar peduncle and terminate on the Purkinje and granule cells in all parts of the cerebellar cortex. They are of two types: dopaminergic fibers, which arise in the ventral mesencephalic tegmentum and project to the interpositus and dentate nuclei and to the granule and Purkinje cells throughout the cortex, and serotonergic neurons, which are located in the raphe nuclei of the brainstem and project diffusely to the granule cell and molecular layer. The granule cell axons elaborate the excitatory transmitter glutamate. All the inhibitory cerebellar cortical neurons appear to utilize GABA. The neurotransmitters of the deep nuclei have not been fully elucidated.
Joseph Babinski and Gordon Holmes cogently analyzed the disturbances of movement and posture that result from lesions of the human cerebellum. For Babinski, the essential function of the cerebellum was the orchestration of muscle synergies in the performance of voluntary movement. A loss or impairment of this function—i.e., asynergia or dyssynergia—resulted in irregularity or fragmentation of the normal motor sequences involved in any given act. This deficit, most apparent in the execution of rapidly alternating movements, was referred to by Babinski as dysor adiadochokinesis, as discussed below. He also pointed out that this was accompanied by certain maladjustments of stance and by catalepsy (perseveration of a posture), features that are not considered prominent by modern observers.
Holmes summarized the effects of cerebellar disease as being in the acceleration and deceleration of movement. He characterized these in a more fundamental way as defects in the rate, range, and force of movement, resulting in an undershooting or overshooting of the target. He used the term “decomposition” to describe the fragmentation of a smooth movement into a series of irregular, jerky components. The terminal tremor, traditionally called intention tremor, and the inability to check the displacement of an outstretched limb, both of which Holmes elegantly described, were attributed to hypotonia, a mechanism no longer accepted.
Parts of the hypotheses of both Babinski and Holmes have been sustained by modern physiologic and clinical studies. In an analysis of rapid (ballistic) movements,
Hallett and colleagues have demonstrated that with cerebellar lesions, there is a prolongation of the interval between the commanded act and the onset of movement. More prominently, there is a derangement of the normal ballistic triphasic agonist–antagonist–agonist motor sequence, referred to in Chaps. 3 and 4. The agonist burst may be too long or too short, or it may continue into the antagonist burst, resulting in excessive agonist–antagonist cocontraction at the onset of movement. These findings may explain what was described by Babinski and Holmes as asynergia, decomposition of movement, but they certainly explain dysmetria. Diener and Dichgans confirmed these fundamental abnormalities in the timing and amplitude of reciprocal inhibition and of cocontraction of agonist–antagonist muscles and remarked that these were particularly evident in pluriarticular movements.