These concepts were based largely on the experimental work of Whittier and Mettler and of Carpenter, in the late 1940s. These investigators demonstrated, in monkeys, that a disorder, which they termed choreoid dyskinesia, could be brought about in the limbs of one side of the body by a lesion localized to in the opposite subthalamic nucleus. They also showed that for such a lesion to provoke dyskinesia, the adjacent pallidum and pallidofugal fibers had to be preserved; that is, a second lesion—placed in the medial segment of the pallidum, in the fasciculus lenticularis, or in the ventrolateral thalamus—abolished the dyskinesia. This experimental hyperkinesia could also be abolished by interruption of the lateral corticospinal tract but not by sectioning of the other motor or sensory pathways in the spinal cord. These observations were interpreted to mean that the subthalamic nucleus exerts an inhibitory or regulating influence on the globus pallidus and ventral thalamus. Removal of this influence by selective destruction of the subthalamic nucleus is expressed physiologically by an irregular activity that is now identified as chorea, presumably arising from the intact pallidum and conveyed to the ventrolateral thalamic nuclei, thence by thalamocortical fibers to the ipsilateral premotor cortex, and from there, to the motor cortex, all in a serial manner.
A general principle that has withstood the test of time is the central role of the ventrolateral and ventroanterior nuclei of the thalamus. Together, these nuclei form a nexus, not only from the basal ganglia but also from the cerebellum, to the motor and premotor cortex. Thus, both basal ganglionic and cerebellar influences are brought to bear, via thalamocortical fibers, on the corticospinal system and on other descending pathways from the cortex. Direct descending pathways from the basal ganglia to the spinal cord are relatively insignificant.
It is currently proposed on the basis of physiologic, lesional, and pharmacologic studies that there are two main efferent projections from the putamen. There are reasons to conceptualize: (1) a direct efferent system from the putamen to the medial (internal) pallidum and then to the substantia nigra, particularly to the pars reticulata, and (2) an indirect system originating in the putamen that traverses the lateral (external) pallidum and continues to the subthalamic nucleus, with which it has strong reciprocal connection. To these, has been added (3) a hyperdirect pathway that activates the subthalamic nucleus directly from the motor cortex, without the necessity of the intervening striatum.
In most ways, the subthalamic nucleus and lateral pallidum operate as a single functional unit, (at least in terms of the effects of lesions in those locations on parkinsonian symptoms and the neurotransmitters involved. The internal (medial) pallidum (GPi) and reticular part of the substantia nigra can be viewed in a similar unitary way, sharing the same input and output patterns. Within the indirect pathway, an internal loop is created by projections from the subthalamic nucleus to the medial segment of the pallidum and pars reticulata. A second offshoot of the indirect pathway consists of projections from the external (lateral) pallidum (GPe) to the medial pallidonigral output nuclei. A complete account of this intricate connectivity cannot be given, but the main themes outlined here seem valid and are to be found in the review by Obeso and colleagues.