Deep brain stimulation (DBS) improves debilitating symptoms of movement disorders when conventional medical therapies, cell transplant strategies, and the delivery of gene-delivered growth factors fail. Despite the remarkable efficacy of DBS, its therapeutic mechanism remains unclear. There is controversy regarding whether the therapeutic effects of DBS are associated with inhibition or excitation of target neurons, the introduction of new activity into the network, or a combination of these mechanisms. Additionally, it is unclear why stimulus frequency plays an important role in the clinical response to therapy. The fundamental hypothesis of this proposal is that unilateral subthalamic nucleus (STN) DBS in PD alters neuronal activity in the bilateral basal ganglia-thalamic-cortical motor system in a manner that is dependent on stimulation frequency. The following specific hypotheses will be tested in PD patients with unilateral STN DBS: (1) High frequency unilateral STN DBS in PD increases antidromic and orthodromic activation of contralateral STN neurons to a greater extent than low frequency stimulation. Preliminary findings of antidromic and orthodromic responses of STN neurons to contralateral DBS will be further explored using microelectrode recordings of STN neurons during contralateral high and low frequency STN DBS. Analyses will employ auto- and cross-correlograms and peristimulus rasters with histograms and Z-scores. (2) High frequency unilateral STN DBS in PD improves ipsilateral bradykinesia more than low frequency stimulation. Kinematic testing in the bilateral extremities of central and peripheral reaction time and movement time will be obtained at high and low stimulation frequencies during a wrist flexion/extension task and analyzed with ANOVA. (3) Unilateral STN DBS in PD alters activity in the ipsilateral premotor cortex. Magnetoencephalography (MEG) will measure the kinetics and localization of cortical magnetic fields evoked by high and low frequency STN DBS. Event detection, averaging, and peak detection will measure the kinetics of the evoked responses, and source localization will be calculated with single and two dipole models. As DBS is investigated for a wide variety of potential indications in neurology and psychiatry, there is a growing need to understand how it modulates brain activity to exert its clinical effects. Gaining such knowledge has the potential to improve the efficacy and safety of DBS in established indications and to guide future therapeutic innovations.
Deep brain stimulation (DBS) improves debilitating symptoms of movement disorders when conventional therapies fail. As DBS is investigated for a wide variety of potential indications in neurology and psychiatry, there is a growing need to understand how it modulates brain activity to exert its clinical effects. Gaining such knowledge has the potential to improve the efficacy and safety of DBS in established indications and to guide future therapeutic innovations.
|Birchall, Elizabeth L; Walker, Harrison C; Cutter, Gary et al. (2017) The effect of unilateral subthalamic nucleus deep brain stimulation on depression in Parkinson's disease. Brain Stimul 10:651-656|
|Amara, Amy W; Walker, Harrison C; Joop, Allen et al. (2017) Effects of subthalamic nucleus deep brain stimulation on objective sleep outcomes in Parkinson's disease. Mov Disord Clin Pract 4:183-190|
|Almeida, Leonardo; Rawal, Pawan V; Ditty, Benjamin et al. (2016) Deep Brain Stimulation Battery Longevity: Comparison of Monopolar Versus Bipolar Stimulation Modes. Mov Disord Clin Pract 3:359-366|
|Rinker 2nd, John R; Salter, Amber R; Walker, Harrison et al. (2015) Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey. BMJ Open 5:e006714|
|Brosius, Stephanie N; Gonzalez, Christopher L; Shuresh, Joshita et al. (2015) Reversible improvement in severe freezing of gait from Parkinson's disease with unilateral interleaved subthalamic brain stimulation. Parkinsonism Relat Disord 21:1469-70|
|Patel, Daxa M; Walker, Harrison C; Brooks, Rebekah et al. (2015) Adverse events associated with deep brain stimulation for movement disorders: analysis of 510 consecutive cases. Neurosurgery 11 Suppl 2:190-9|
|Rawal, Pawan V; Almeida, Leonardo; Smelser, Luke B et al. (2014) Shorter pulse generator longevity and more frequent stimulator adjustments with pallidal DBS for dystonia versus other movement disorders. Brain Stimul 7:345-9|
|Sung, Victor W; Watts, Ray L; Schrandt, Christian J et al. (2013) The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease. J Neurosurg 119:1530-6|
|Walker, Harrison C; Huang, He; Gonzalez, Christopher L et al. (2012) Short latency activation of cortex by clinically effective thalamic brain stimulation for tremor. Mov Disord 27:1404-12|
|Walker, Harrison C; Huang, He; Gonzalez, Christopher L et al. (2012) Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease. Mov Disord 27:864-73|
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