Faculty Bibliography

Motor control is defined as the process of restricting the output of the motor nervous system so that meaningful and coordinated behavior ensues. The high dimensionality of the computation underlying motor control is presented and a simplifying framework is outlined. Evidence that movements are performed non-continuously is reviewed as is the construct of the 'motor synergy' as a fundamental unit of control. It is proposed that the pulsatile nature of movement and the tendency of muscle collectives to be activated as synergies reflect processes that the nervous system has evolved to reduce the dimensionality of motor control. We propose that the inferior olive simplifies the computation underlying motor control by biasing the activities of spinal and cranial motor systems so that discrete collectives of muscles are predisposed to contract at specific times during movement. The well-characterized oscillatory activity of olivary neurons is postulated to provide a pacemaking signal and to restrict the control process to particular moments in time while the process of electrotonic coupling and uncoupling of assemblies of olivary neurons is proposed to underlie the spatial distribution of synergic muscle activations. It is proposed that the olivocerebellar contribution to the control process is to allow movements to be executed rapidly in a feedforward manner, so that the need for sensory guidance and feedback is minimized

1. The role of gamma-aminobutyric acid (GABA) on the pattern generation properties of neuronal ensembles in the olivocerebellar system was studied utilizing multiple electrode recordings of complex spikes (CSs) from rat crus 2a Purkinje cells (PCs). Initially multiple electrode experiments were combined with microinjections of picrotoxin into the inferior olive (IO). To corroborate the picrotoxin findings, the cerebellar nuclei, a major source of the GABAergic terminals in the IO, were chemically lesioned with the use of microinjections of kainic acid and N-methyl-D-aspartate. Both procedures generated comparable results. 2. After intraolivary picrotoxin injection there was an increase in the average firing rate, synchrony, and rhythmicity of spontaneous CS activity. In addition, the neuronal oscillation frequency tended to shift to lower frequencies. 3. The spatial distribution of synchronous CS activity in control conditions displayed a predominantly rostrocaudal orientation. Injection of picrotoxin to the IO disrupted this rostrocaudal organization and led to synchronous CS activity among PCs throughout crus 2a. Similar effects were observed relating to the distribution of CSs evoked via the 'climbing fiber reflex,' in which antidromic activation of the climbing fibers is followed by a return excitation that is mediated by the gap junctions between olivary neurons. 4. Chemical lesions of the cerebellar nuclei resulted in increased CS average firing rates. The effect of the lesions on CS synchronicity was similar to that following the picrotoxin injections, but greater in magnitude. In contrast to the olivary picrotoxin injections, the cerebellar nuclear lesions did not lead to an enhanced CS rhythmicity. 5. Bilateral recordings from left and right crus 2a demonstrated significant interhemispheric synchronization of CS activity, consistent with a previous report. Both unilateral olivary injections of picrotoxin and unilateral cerebellar nuclear lesions resulted in increased synchronization of CS activity between the left and right crus 2a. 6. We conclude that the cerebellar nucleoolivary projection to the olivary glomeruli modulates the effective electrotonic coupling between olivary neurons, and thereby carves out ensembles of neurons whose activity is synchronized. Thus these two nuclei may form the basis for a flexible and sophisticated motor coordination system able to help generate the many distinct movements that organisms are capable of performing

OBJECTIVE: To expand the use of magnetoencephalography (MEG) functional mapping in the operating room as well as preoperatively, a method of integrating the MEG sensorimotor mapping information into a stereotactic database, using computed tomographic scans, magnetic resonance imaging scans, and digital angiography, was developed. The combination of functional mapping and the stereotactic technique allows simultaneous viewing of the spatial relationship between the MEG-derived functional mapping, the radiological/structural anatomic characteristics, and the pathological abnormality. METHODS: MEG data were collected using a MAGNES II Biomagnetometer and were incorporated into the COMPASS frame-based and REGULUS frameless stereotactic systems. The transformation process, by calculating a translational vector and a rotation matrix, integrates functional and anatomic information that is then directly available intraoperatively in the stereotactic database. This procedure was employed in 10 patients undergoing computer-assisted stereotactic volumetric resections for lesions involving the sensorimotor cortex. The principles of coregistration and coordinate transformation are reviewed in the context of preoperative functional mapping. We introduce innovations to apply these techniques to intraoperative stereotactic systems. RESULTS: Tests of the accuracy of the intraoperative integration of functional information in patients and calibration phantoms indicated close agreement with earlier preoperative methods. The intraoperative availability of functional information was a significant aid to the surgeon because it provided more accurate information on the location of functional tissue than could be derived solely by radiological criteria. CONCLUSION: The real-time availability of functional mapping information in an interactive fashion can reduce surgical risk and minimize functional morbidity. Within the ever-expanding realm of functional mapping and image-guided neurosurgery, further progress and integration of these methods is critical for resection of lesions involving eloquent cortex

Simultaneous recordings of the left and right crus IIA of the cerebellar cortex in the rat have demonstrated that Purkinje cells of both sides can be activated synchronously by their climbing fibers. Because climbing fibers arise exclusively from the contralateral inferior olive (IO), this physiological finding seems to contradict the anatomy. To define the structural basis responsible for the bilateral synchrony, we examined the possibilities that bilateral common afferent inputs to the IO and interolivary connections form the underlying mechanisms. The bilaterality of the major afferents of the olivary regions that project to crus IIA was studied using Phaseolus vulgaris leucoagglutinin as an anterograde tracer. We found that the excitatory and inhibitory projections from the spinal trigeminal nucleus and dorsolateral hump of the interposed cerebellar nucleus to the transition area between the principal olive and dorsal accessory olive were bilateral. A second possible mechanism for bilateral synchrony, which is the possibility that axons of olivary neurons provide collaterals to the contralateral side, was investigated using biotinylated dextran amine as an anterograde tracer. Labeled axons were traced and reconstructed from the principal olive and dorsal and medial accessory olive up to the entrance of the contralateral restiform body. None of these axons gave rise to collaterals. The possibility that neurons in the left and right IO are electronically coupled via dendrodendritic connections was investigated by examining the midline region of the IO. The neuropil of the left and right IO is continuous in the dorsomedial cell column. Examination of Golgi impregnations of this subdivision demonstrated that (1) many dendrites cross from one side to the other, (2) neurons close to the midline give rise to dendrites that extend into both olives, and (3) dendrites of neurons in the dorsomedial cell column frequently traverse into adjacent olivary subdivisions such as the medial accessory olive and the transition area between the principal olive and dorsal accessory olive. Sections immunostained for dendritic lamellar bodies or GABAergic terminals showed the same pattern: the neuropils of the dorsomedial cell columns on both sides form a continuum with each other as well as with the neuropil of other adjacent olivary subdivisions. Ultrastructural examination of the dorsomedial cell column demonstrated that the midline area includes many complex glomeruli that contain dendritic spines linked by gap junctions. To verify whether the complex spike synchrony observed between left and right crus IIA could indeed be mediated in part through coupled neurons in the dorsomedial cell column, we recorded simultaneously from crus IIA areas and from left and right vermal lobule IX, which receives climbing fibers from the dorsomedial cell column. In these experiments we demonstrated that the climbing fibers of all four areas, i.e., the left and right crus IIA as well as the left and right lobule IX, can fire synchronously. The present results indicate that synchronous climbing fiber activation of the left and right crus IIA in the rat can be explained by (1) bilateral inputs to the transition areas between the principal olive and dorsal accessory olive and (2) dendrodendritic electrotonic coupling between neurons of the left and right dorsomedial cell column and between neurons of the dorsomedial cell column and adjacent olivary subdivisions

A variety of clinical and experimental findings suggest that parkinsonian resting tremor results from the involuntary activation of a central mechanism normally used for the production of rapid voluntary alternating movements. However, such central motor loop oscillations have never been directly demonstrated in parkinsonian patients. Using magnetoencephalography, we recorded synchronized and tremor-related neuromagnetic activity over wide areas of the frontal and parietal cortex. The spatial and temporal organization of this activity was studied in seven patients suffering from early-stage idiopathic Parkinson's disease (PD). Single equivalent current dipole (ECD) analysis and fully three-dimensional distributed source solutions (magnetic field tomography, MFT) were used in this analysis. ECD and MFT solutions were superimposed on high-resolution MRI. The findings indicate that 3 to 6 Hz tremor in PD is accompanied by rhythmic subsequent electrical activation at the diencephalic level and in lateral premotor, somatomotor, and somatosensory cortex. Tremor-evoked magnetic activity can be attributed to source generators that were previously described for voluntary movements. The interference of such slow central motor loop oscillations with voluntary motor activity may therefore constitute a pathophysiologic link between tremor and bradykinesia in PD

In a previous study, fluorescence labeling of a plasmalemmal ATPase protein with the 5F10 monoclonal antibody revealed prominent antigen in the cerebellar molecular layer surrounding the somata and dendrites of Purkinje cells. In the present study, this antibody labeled with silver enhanced nano-sized gold particles on semithin plastic sections revealed a clearly demarcated plasma membrane outlining the somata and entire dendritic arbors of Purkinje cells including their spines. Ultrastructural analysis of horseradish peroxidase preparations showed reaction product along the plasmalemma and extending on to the sub-plasmalemmal endoplasmic reticulum. In the granular layer, somata of granule cells were reactive, as were their dendritic extensions into glomeruli where reactive claws surrounded voids formed by mossy fiber rosettes. Somata and dendrites of cerebellar nuclear cells also had reactive zones that were limited to the plasma membrane and a narrow zone of the sub-plasmalemmal endoplasmic reticulum. Comparative labeling of this protein and P channel protein revealed similar plasmalemmal locations. This study shows that a specific calcium ATPase pump protein is located on the plasmalemma of certain types of cerebellar neurons. The ultrastructural distribution of calcium pump and P channel antibodies occurred in punctate sites along the plasma membrane of dendrites and spines of Purkinje cells. The close association between P-type calcium channels and the plasma membrane calcium pump is consistent with rapid extrusion of intracellular calcium from neurons endowed with large numbers of voltage-gated calcium channels