Basal Ganglia In Motor Control Research Articles

The cortico-striatal circuitry in autism-spectrum disorders: a balancing act.

The basal ganglia are major targets of cortical inputs and, in turn, modulate cortical function via their projections to the motor and prefrontal cortices. The role of the basal ganglia in motor control and reward is well documented and there is also extensive evidence that they play a key role in social and repetitive behaviors. The basal ganglia influence the activity of the cerebral cortex via two major projections from the striatum to the output nuclei, the globus pallidus internus and the substantia nigra, pars reticulata. This modulation involves a direct projection known as the direct pathway and an indirect projection via the globus pallidus externus and the subthalamic nucleus, known as the indirect pathway. This review discusses the respective contribution of the direct and indirect pathways to social and repetitive behaviors in neurotypical conditions and in autism spectrum disorders.

Attenuation of neural responses in subthalamic nucleus during internally guided voluntary movements in Parkinson's disease.

The proposed models of segregated functional loops describe the organization of motor control over externally triggered (ET) and internally guided (IG) movements. The dopamine deficiency in Parkinson’s disease (PD) is considered to cause a disturbance in the functional loop regulating IG movements. At the same time, the neural mechanisms of movement performance and the role of basal ganglia in motor control remain unclear.The aim of this study was to compare neuronal responses in the subthalamic nucleus (STN) during ET and IG movements in PD. We found and analyzed 26 sensitive neurons in 12 PD patients who underwent surgery for implantation of electrodes for deep brain stimulation. We also analyzed the local field potentials (LFP) of the STN of six patients during the postoperative period. Patients were asked to perform voluntary movements (clenching and unclenching the fist) evoked by verbal command (ET) or self-initiated (IG). We showed heterogeneity of neuronal responses and did not find sensitive neurons associated with only one type of movement. Most cells were characterized by leading responses, indicating that the STN has an important role in movement initiation. At the same time, we found attenuation of motor responses during IG movement vs. stable responses during ET movements. LFP analysis also showed attenuation of beta desynchronization during multiple IG movements.We propose that stable neuronal response to ET movements is associated with the reboot of the motor program for each movement, while attenuation of responses to IG movement is associated with single motor program launching for multiple movements.

Noninvasive brain stimulation for Parkinson's disease

In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep-brain-stimulation (DBS) and advances in the understanding of PD pathophysiology have raised interest in noninvasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. Most trials of noninvasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS) targeting the motor cortex. The current studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence/quality-of-life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters, which derive their rationale from studies on brain physiology. These novel parameters intend to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control and its contribution to the pathogenesis of motor disorders.

T002 Non-invasive brain stimulation for Parkinson’s disease

In advanced Parkinson’s disease (PD), the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation(DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. Most trials of non-invasive brain stimulation in PD have applied repetitive trans-cranial magnetic stimulation(rTMS) targeting the primary motor cortex and cortical areas of the motor circuit. The current studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters, which derive their rationale from studies on brain physiology. These novel parameters intend to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control and its contribution to the pathogenesis of motor disorders. There may be a diagnostic potential of TMS in better characterizing individual traits in the perspective of personalized medicine.

Non-invasive brain stimulation for Parkinson's disease: Current concepts and outlook 2015.

In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. Most trials of non-invasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex and cortical areas of the motor circuit. Published studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence and quality of life. Approaches to potentiate the efficacy of rTMS, including increasing stimulation intensity and novel stimulation parameters, derive their rationale from studies of brain physiology. These novel parameters simulate normal firing patterns or act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control. There may also be diagnostic potential of TMS in characterizing individual traits for personalized medicine.

Schizophrenia: A Computational Reinforcement Learning Perspective

As one of the most complex neurocognitive disorders, schizophrenia (SZ) is a devastating condition for which the underlying sources are far from being fully understood. Indeed, it is likely that there are multiple etiologies to the disease and heterogeneity within the population. Moreover, it is impossible to understand from a purely mechanistic basis how a patient would come to believe so strongly in delusions as to, for example, gouge out his own eyes. Nevertheless, science marches forward, and the last 30 years or so have produced a wealth of knowledge regarding some of the risk factors, genetics, pharmacology, cognitive deficits, and underlying neurobiology associated with the disease. In part because of the efficacy of antipsychotic treatments via dopamine D2 receptor blockade, the majority of this research focuses on dysfunctions of the dopaminergic system, in both frontal cortex and basal ganglia, thought to be related to negative and positive symptoms, respectively. At the neurocognitive level,muchof the focushasbeenondysfunctionwithin dorsolateralprefrontal cortical circuits and their contributions to working memory, cognitive control, and attentional shifting. While dopamine plays a critical role in all these processes, it is perhaps more centrally related to aspects of motivational processing, which is surprisingly understudied in SZ. Indeed, it is possible to account for many of the frontal-dependent cognitive deficits in SZbypositingamore coredeficit in themotivational ‘‘gating’’ system for determining which information patients should ‘‘care’’ about and what they might ignore. Given the complexity of neural circuits involved in both cognitive and motivational functions, it becomes dauntingly difficult to capture the possible interactions of these circuits, and particularly how they are disrupted in SZ, with simple verbal depictions and static anatomical diagrams. Here I consider the potential application of computational neural network models as a principled and dynamic tool for exploring these interactions and psychopathology associated with dopaminergic dysfunction in SZ and which can lead to new testable predictions at both the neural and behavioral levels. These models enable one to simulate various anatomical and physiological pieces of data, using mathematical equations that capture how groups of neurons communicate activity to other neurons within and between brain areas. By incorporating aspects of neuronal physiology, connectivity, and synaptic plasticity within the basal ganglia–frontal cortical system, one can examine dynamics of this circuitry and how it may go awry. At the same time, it is not tractable to try to incorporate every known biological detail into a model, particularly when the goal is to discover how an entire system of brain regions interact to produce behavior. Thus, the models are also constrained by the need to account for existing data at these higher levels, such as effects of focal lesions or pharmacological manipulation on behavior. Critically, the models make new predictions about how the system works that would likely not have emerged otherwise and often were not conceived by the modeler prior to being built. Models can then be tested and refined and their implications explored in neurological conditions. To sum up a large body of basic research, models of frontostriatal function have generally suggested that these circuits support the following—(1) action selection: as in when making a choice among multiple competing alternatives and (2) reinforcement learning: as in modifying expectations and behavior following positive and negative outcomes. For the former process, ‘‘actions’’ to be selected include both lower level motor programs, consistent with the traditionally ascribed role of the basal ganglia in motor control, and higher level cognitive actions, such as when and when not to update/manipulate the contents of working memory. Reinforcement learning then operates on these actions such that adaptive actions are more likely to be repeated, whereas maladaptive actions are suppressed. Critically, according to both the models and available electrophysiological evidence, positive outcomes are reflected in terms of deviations from current expectations, a term referred to as a ‘‘positive prediction error,’’ and are encoded by phasic bursts of dopamine. Similarly, negative prediction errors are encoded by phasic dips or pauses in dopaminergic activity. These phasic bursts and dips modify corticostriatal synaptic plasticity, allowing the system To whom correspondence should be addressed; tel: 520-626-4787, fax: 520-621-9306, e-mail: mfrank@u.arizona.edu. Schizophrenia Bulletin doi:10.1093/schbul/sbn123

Imaging basal ganglia function

In this review, the value of functional imaging for providing insight into the role of the basal ganglia in motor control is reviewed. Brain activation findings in normal subjects and Parkinson's disease patients are examined and evidence supporting the existence for functionally independent distributed basal ganglia-frontal loops is presented. It is argued that the basal ganglia probably act to focus and filter cortical output, optimising the running of motor programs.

Irving S. Cooper (1922-1985): a pioneer in functional neurosurgery.

Irving S. Cooper (1922-1985), the son of a salesman, worked his way through high school, college, and medical school to become one of the pioneers in functional neurosurgery. He developed several novel techniques for the surgical management of Parkinson's disease and other crippling movement disorders. A keen interest in the physiology of movement disorders was kindled by his doctoral research and continued during his neurosurgical training. He began to apply this knowledge to surgical practice in 1952 when he began his faculty career as Assistant Professor of Surgery at New York University. At the time, surgical treatment of parkinsonian tremor focused on various techniques used to interrupt the pyramidal tract. During a subtemporal approach for a cerebral pedunculotomy, he inadvertently injured and, subsequently, was forced to occlude the anterior choroidal artery. Much to Cooper's surprise, following emergence from anesthesia the patient's tremor and rigidity were abolished without any residual hemiparesis. This serendipitous observation, together with Meyer's earlier work on the role of the basal ganglia in motor control, helped focus surgical efforts on targets within the basal ganglia and, subsequently, within the thalamus to alleviate the movement disorders associated with Parkinson's disease. While at New York University, Cooper developed chemopallidectomy and, later at St. Barnabas Hospital in the Bronx (1954-1977), he used cryothalamectomy as a surgical technique for primary control of tremor in patients with Parkinson's disease. Cooper authored many original papers on surgical techniques and several textbooks on the lives of patients afflicted with Parkinson's disease and other crippling movement disorders. Although considered controversial, this fascinating and complex neurosurgeon made significant contributions to this field.

Motor dominance and lateral asymmetry of the globus pallidus.

Animal experiments suggest that neurochemical and anatomic asymmetries exist within the basal ganglia, particularly the globus pallidus, and that these asymmetries correlate with both preferred direction of rotation and limb preference in lever pressing. Human neurotransmitter studies have also revealed a significant asymmetry within the globus pallidus, the left containing greater amounts of dopamine and choline acetyltransferase than the right. Recent anatomic studies of human subcortical regions, limited to the striatum, have failed to show a size asymmetry. We examined 18 normal brains in subjects ranging in age from 26 weeks gestation to 86 years for volumetric asymmetry of the globus pallidus. We found a significant asymmetry, the left side measuring larger in 16 of 18 brains. Considering the role of the basal ganglia in motor control, this data may reflect a structural basis of either axial or limb motor dominance in humans.

Basal ganglia outputs and motor control.

Several lines of evidence suggest that the role of the basal ganglia in motor control is of a higher order than control of movements per se. First the striatum receives inputs from cortical areas that subserve mnemonic and other cognitive processes. Furthermore, the supplementary motor area (a zone that receives outputs from the globus pallidus via thalamus) exhibits changes in neuronal discharge and metabolic activity during movement planning as well as during movement. It is possible that this activity reflects its pallidal inputs. In addition, cells in another part of the basal ganglia, the pars reticulata of the substantia nigra, exhibit activity that reflects mnemonic as well as oculomotor and visual processes. Finally, there are striatal neurons that respond to stimuli when these stimuli trigger movement but not when responses to the stimuli are extinguished. Taken collectively, these observations are consistent with the view that the basal ganglia may provide an interface between motor centres and cortical areas for higher brain function.