Visually Guided Movements Suppress Subthalamic Oscillations in Parkinson's Disease Patients
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There is considerable evidence that abnormal oscillatory activity in the basal ganglia contributes to the pathogenesis of Parkinson's disease. However, little is known regarding the relationship of oscillations to volitional movements. Our goal was to evaluate the dynamics of oscillatory activity at rest and during movement. We performed microelectrode recordings from the subthalamic nucleus (STN) of patients undergoing deep brain stimulation surgery. During recordings, the patients used a joystick to guide a cursor to one of four targets on a monitor. We recorded 184 cells and 47 pairs of cells in 11 patients. At rest, 26 cells (14%) demonstrated significant oscillatory activity, with a mean frequency of 18 Hz. During movement, this oscillatory activity was either reduced or completely abolished in all of the cells. At rest, 18 pairs (38%) of cells in five patients exhibited synchronized oscillatory activity, with a mean frequency of 15 Hz. In 17 of the 18 pairs, both of the cells exhibited oscillations, and, in one pair, only one of the cells was oscillatory. These synchronized oscillations were also significantly decreased with movement. There was a strong inverse correlation between firing rates and oscillatory activity. As the firing rates increased with movement, there was a decrease in oscillatory activity. These findings suggest that visually guided movements are associated with a dampening and desynchronization of oscillatory activity in STN neurons. One possible explanation for these observations is that the increased cortical drive associated with movement preparation and execution leads to a transient dampening of STN oscillations, hence facilitating movement.Keywords:
Subthalamic Nucleus
Premovement neuronal activity
Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) is widely used in advanced stages of Parkinson's disease(PD) and has proven to be an effective treatment of the various motor symptoms. The therapy involves implanting a lead consisting of multiple electrodes in the STN through which continues high frequency electric pulses are delivered. The clinical outcome highly depends on the location of the electrodes within the STN. However, despite careful planning
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Deep brain stimulation (DBS) represents a major advance in the treatment of Parkinson’s disease (PD). As more neurosurgeons enter this field, technical descriptions of implantation techniques are needed. Here we present our technical approach to subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS implantation, based on 180 STN implants and 75 GPi implants. The essential steps in DBS implantation are magnetic resonance imaging (MRI)-guided stereotactic localization, confirmation of the motor territory of the target nucleus with microelectrode mapping, and intra-operative test stimulation to determine voltage thresholds for stimulation-induced adverse effects. Lead locations are documented by postoperative MRI in all cases.
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Abstract Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of Parkinson's disease. Although a range of psychiatric and behavioral problems have been documented following deep brain stimulation, the short‐term effects of subthalamic nucleus stimulation on patients' mood have only been investigated in a few studies. Our aim was to compare self‐reported mood in Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON versus OFF. Twenty‐three Parkinson's patients with bilateral deep brain stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients completed a mood visual analogue scale twice. Operated patients were tested with deep brain stimulation of the subthalamic nucleus both ON and OFF. All were assessed on medication. The operated Parkinson's group reported feeling significantly better coordinated, stronger, and more contented with deep brain stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a positive direction when deep brain stimulation of the subthalamic nucleus was ON. When changes in motor scores were taken into account, the operated patients still reported feeling better‐coordinated, but also less gregarious with stimulation ON. Unoperated Parkinson's patients showed no differences on any of these measures between their 2 ratings. Short‐term changes in deep brain stimulation of the subthalamic nucleus have a small and mostly positive effect on mood, which may be partly related to improvements in motor symptoms. The implications for day‐to‐day management of patients with deep brain stimulation of the subthalamic nucleus are discussed. © 2012 Movement Disorder Society
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S. H. Wong*a, P. R. Eldridgeb, A. Duffya, S. H. Fox*c, T. R. K. Varmab & N. A. Fletcheraa Departments of Neurology1b Neurosurgery2, The Walton Centre, Liverpool, UKc Movement Disorders Clinic, University of Toronto, Toronto Western Hospital, Ontario, Canada
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Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS.
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The current popularity and widespread acceptance of deep brain stimulation (DBS) for Parkinson's disease (PD) began in the early 1990s after publications from teams in Grenoble and Lille introduced the concept of DBS to ameliorate abnormal movements without destroying tissue. The most common targets for DBS in PD are the ventral intermediate nucleus (Vim), globus pallidus internus (GPi), and subthalamic nucleus (STN). Currently, DBS of the STN is the most common surgical procedure for PD. This chapter highlights this operation and discusses (i) the rationale for neurostimulation of the STN, (ii) referral criteria to select the ideal patient, (iii) outcome, (iv) stimulation parameters, and (v) potential side effects and complications.
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