Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output
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Abstract:
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.Keywords:
Subthalamic Nucleus
Medium spiny neuron
Local field potential
<i>Aims:</i> Spectral analysis of local field potential (LFP) recorded by deep brain stimulation (DBS) electrode around the subthalamic nucleus (STN) in patients with Parkinson’s disease was performed. <i>Methods:</i> The borders of the STN were determined by microelectrode recording. The most eligible trajectory for the sensorimotor area of the STN was used for LFP recording while advancing the DBS electrode. <i>Results:</i> The low-frequency LFP power (θ- to β-band) increased from a few millimeters above the dorsal border of the STN defined by microelectrode recording; however, the low-frequency power kept the same level beyond the ventral border of the STN. Only high β-power showed close correlation to the dorsal and ventral borders of the STN. <i>Conclusions:</i> A spectral power analysis of LFP recording by DBS electrode helps with the final confirmation of the dorsal and ventral borders of the STN of Parkinson’s disease in DBS implantation surgery.
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To evaluate the nature of oscillatory activity in the
subthalamic nucleus (STN) by means of intraoperative local field potential (LFP) recordings, its relationship with microelectrode recordings (MER) and its potential use to locate the STN and its sensorimotor sub-area in patients with Parkinson’s disease during deep brain stimulation (DBS) surgery.
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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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In the past years, local field potential (LFP) signals recorded from the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) for Parkinson's disease (PD) disclosed that DBS has a controversial effect on STN beta oscillations recorded 2–7 days after surgery for macroelectrode implantation. Nothing is known about these DBS-induced oscillatory changes 30 days after surgery. We recorded STN LFPs during ongoing DBS in 7 patients with PD, immediately (hyperacute phase) and 30 days (chronic phase) after surgery. STN LFP recordings showed stationary intranuclear STN beta LFP activity in hyperacute and chronic phases, confirming that beta peaks were also present in chronic recordings. Power spectra of nuclei with significant beta activity (54% of the sample) showed that it decreased significantly during DBS (p = 0.021) under both recording conditions. The time course of beta activity showed more evident DBS-induced changes in the chronic than in the hyperacute phase (p = 0.014). DBS-induced changes in STN beta LFPs in patients undergoing DBS in chronic phase provide useful information for developing a new neurosignal-controlled adaptive DBS system.
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