Michael D. Crutcher

Do cortical and basal ganglionic motor areas use motor programs to control movement

Prevailing engineering-inspired theories of motor control based on sequential/algorithmic or motor-programming models are difficult to reconcile with what is known about the anatomy and physiology of the motor areas. This is partly because of certain problems with the theories themselves and partly because of features of the cortical and basal ganglionic motor circuits that seem ill-suited for most engineering analyses of motor control. Recent developments in computational neuroscience offer more realistic, that is, connectionist, models of motor processing. The distributed, highly parallel, and nonalgorithmic processes in these models are inherently self-organizing and hence more plausible biologically than their more traditional algorithmic or motor-programming counterparts. The newer models also have the potential to explain some of the unique features of natural, brain-based motor behavior and to avoid some of the computational dilemmas associated with engineering approaches.

Normalizing motor-related brain activity Subthalamic nucleus stimulation in Parkinson disease

Objective: To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Methods: Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. Results: For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related “overactivity” compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Conclusions: Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

Target-, limb-, and context-dependent neural activity in the cingulate and supplementary motor areas of the monkey

Very little is known about the role of the cingulate motor area (CMA) in visually guided reaching compared to other cortical motor areas. To investigate the hierarchical role of the caudal CMA (CMAc) during reaching we recorded the activity of neurons in CMAc in comparison to the supplementary motor area proper (SMA) while a monkey performed an instructed delay task that required it to position a cursor over visual targets on a computer screen using two-dimensional (2D) joystick movements. The direction of the monkey’s arm movement was dissociated from the direction of the visual target by periodically reversing the relationship between the direction of movement of the joystick and that of the cursor. Neurons that responded maximally with a particular limb movement direction regardless of target location were classified as limb-dependent, whereas neurons that responded maximally to a particular target direction regardless of the direction of limb movement were classified as target-dependent. Neurons whose activity was directional in one of the two visuomotor mapping conditions and non-directional or inactive in the other were categorized as context-dependent. Limb-dependent activity was observed more frequently than target-dependent activity in both CMAc and SMA proper during both the delay period (preparatory activity; CMAc, 17%; SMA, 31%) and during movement execution (CMAc, 49%, SMA, 48%). A modest percentage of neurons with preparatory activity were target-dependent in both CMAc (11%) and SMA proper (8%) and a similar percentage of neurons in both areas demonstrated target-dependent, movement activity (CMAc, 8%; SMA, 10%). The surprising finding was that a very large percentage of neurons in both areas displayed context-dependent activity either during the preparatory (CMAc, 72%; SMA, 61%) or movement (CMAc, 43%, SMA 42%) epochs of the task. These results show that neural activity in both CMAc and SMA can directly represent movement direction in either limb-centered or target-centered coordinates. The presence of target-dependent activity in CMAc, as well as SMA, suggests that both are involved in the transformation of visual target information into appropriate motor commands. Target-dependent activity has been found in the putamen, SMA, CMAc, dorsal and ventral premotor cortex, as well as primary motor cortex. This indicates that the visuomotor transformations required for visually guided reaching are carried out by a distributed network of interconnected motor areas. The large proportion of neurons with context-dependent activity suggests, however, that while both CMAc and SMA may play a role in the visuomotor transformation of target information into movement parameters, their activity is not solely coding parameters of movement, since their involvement in this process is highly condition-dependent.

Anatomical Investigations of the Pallidotegmental Pathway in Monkey and Man

The targets of internal pallidal efferents have attracted considerable attention given the central role proposed for the internal segment of the globus pallidus (GPi) in models of normal and pathological movement.1–3 The previous emphasis of these models on basal ganglia-thalamocortical circuitry, has left pathways between the GPi and the midbrain tegmentum largely unexplored. In the primate, the size and functional import of pallidofugal projections upon the mesopontine tegmentum are nonetheless likely to be significant. A majority of neurons in the primate GPi contribute to this pathway via collateralization from pallidothalamic fibers,4–6 and its terminl zone has been described as “extensive”7. Experimental and pathophysiological observations implicate the mesopontine tegmental region in receipt of basal ganglia output as important in modulating normal and pathological movement. Electrical stimulation and micro infusions of substance-P or NMDA8 into the mesopontine tegmentum in decerebrate subprimate preparations elicit treadmill locomotion, while GABAergic pathways play an inhibitory role8, 9 (i. e. the “mesencephalic locomotor region” (MLR).10–12 In awake behaving subprimates, cytotoxic lesions including, but not restricted to, midbrain tegmental/basal ganglia circuitry produce incomplete hindlimb extension, bradykinesia and dyscoordination.13 Depending on the locus and the electrical or pharamacological stimulus parameters applied, motor effects ranging from decreased “postural support” to increased spontaneous motor activity have also been reported.14–21 Enhanced utilization of 2-deoxyglucose in the mesopontine tegmentum in primate models of Parkinsons disease (PD)22 suggests that excessive pallidotegmental inhibition might contribute to hypokinesia, while decreased utilization in a model of hemiballismus23 suggests that disinhibition of the mesopontine tegmentum might contribute to hyperkinetic disorders.

Tonically Active Neurons in the Striatum of the Monkey Rapidly Signal a Switch in Behavioral Set

It is very well established that the basal ganglia play an important role in the control of movement. In the last 20 years a great deal of convincing evidence has accumulated indicating that the basal ganglia are also involved in much more than just motor functions, including cognition, motivation and reward. For example, it has been proposed that, among other things, the basal ganglia play an important role in learning stimulus-response associations1–4, forming stimulus-reward associations5–6, prediction of upcoming rewards6–8, attention9–12, and the switching of behavioral set13–15. There is a class of striatal interneurons, the tonically active neurons (TANs), whose activity may underlie some of these proposed functions.