Subthalamic Nucleus DBS Sub-harmonic Oscillatory Activity Reflect Presence or Absence of DBS Responsiveness
Bradley Greger1, Markey Olson2, Sydney Felsen2, Baltazar Zavala2, Sankardas Sudeesh3, Holly Shill2, Francisco Ponce2, Sana Aslam2
1Arizona State University, SBHSE, 2Barrow Neurological Institute, 3Arizona State University
Objective:
To correlate DBS sub-harmonics with patient responsiveness and investigate neurophysiological mechanisms subserving DBS induced sub-harmonics.
Background:
DBS induced sub-harmonics have been observed in multiple studies, but the relationship of sub-harmonics to clinical outcomes and underlying neurophysiology is ill-defined.
Design/Methods:
Electrophysiological recordings and MDS-UPDRS III were performed in two DBS patients without dyskinesia biweekly during a 10-week exercise program. Testing was conducted under four conditions (Levodopa/DBS both ON and OFF) during baseline and final visits and ON/ON in the sessions between.
Results:
P009 showed stimulation responsiveness in MDS-UPDRS III scores (55 OFF levodopa/OFF stimulation, 43 ON/OFF, 29 OFF/ON, 25 ON/ON), whereas P010 showed a similar response to medication but was less responsive to stimulation (57, 43, 45, 46). During baseline recordings, P009 (DBS 145 Hz) displayed increased spectral power in two subharmonic frequencies: ~108 Hz (¾ subharmonic, mean-0.086, SD-0.118) and ~72 Hz (½ subharmonic, mean-0.058, SD-0.079) OFF/ON levodopa/DBS. Increased spectral power at ~72 Hz (mean-0.025, SD-0.034) persisted in OFF/OFF. Increased spectral power at DBS sub-harmonic frequencies was not present under any condition in patient P010 (DBS 180 Hz)(mean-0.025, SD-0.0003).
P009 showed increased spectral power at ~108 Hz and ~72 Hz during sessions 1-4. Before session 5, DBS was clinically adjusted to 165 Hz. Increased spectral power was then present at the new subharmonic frequencies (~123 Hz and ~82 Hz) as well as at ~72 Hz (½ original DBS frequency). During the final session, increased spectral power was present at ~123 Hz and ~72 Hz with the patient OFF/OFF.
Conclusions:
DBS induced persistent oscillatory neural activity at DBS sub-harmonic frequencies that may serve as a biomarker for patient responsiveness to DBS therapy. DBS may activate natural resonance frequencies in the STN, or establish persistent oscillatory activity in neural circuitry through neural plasticity.