Graduate Student Seminar Series
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Presentation Title: Multi-modal interrogation of subcortical circuit activations elicited by GPi-DBS
Evoked resonant neural activity (ERNA) occurs during deep brain stimulation (DBS) of
the subthalamic nucleus (STN), and its amplitude is correlated to clinical benefit. In pilot work,
we uncovered that the ERNA waveform is associated with temporally-locked patterned neuronal inhibition in the STN; likely representative of a functional readout of a restorative promotion of GPe (globus pallidus externus) mediated inhibition throughout the basal-ganglia-thalamo-cortical network. Our objective here was to perform physiological and anatomical characterizations of this circuit signature in the globus pallidus internus (GPi), as we hypothesize that ERNA (GPemediated
inhibition) is a necessary mechanistic phenomenon underlying the common efficacy of
STN- and GPi-DBS for Parkinson’s disease (PD).During awake DBS surgeries, intracranial
recordings were acquired using two closely spaced microelectrodes (600 μm spacing), using one for recording and the other for stimulation. Stimulation-induced electrophysiological signals were recorded across the spatial extent of GPi, and the resulting data used to generate interstimulus waveform averages and corresponding peristimulus spike histograms. Distinct neural responses, including ERNA, were identified in the GPi. In addition to ERNA (GPe-mediated inhibition), we have discovered functional readouts of the activation of striatal and STN inputs to GPi. High resolution functional mapping across the GPi anatomy revealed that the ERNA hotspot was associated with the typical therapeutic target for GPi-DBS. ERNA may be clinically useful as a biomarker for targeting the most beneficial location for GPi-DBS. Additionally, ERNA (GPemediated inhibition) may represent a convergent mechanistic circuit theory behind the common efficacy of STN- and GPi-DBS in PD.
Supervisor Name: Luka Milosevic
Year of Study: 2
Program of Study: MASc
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