• Marisa DiMarzio, Radhika Madhavan, Suresh Joel, Ileana Hancu, Eric Fiveland, Julia Prusik, Michael Gillogly, Tanweer Rashid, Jacquelyn MacDonell, Jeffrey Ashe, Ilknur Telkes, Paul Feustel, Michael D Staudt, Damian S Shin, Jennifer Durphy, Roy Hwang, Era Hanspal, and Julie G Pilitsis.
• Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, USA.
• Neuromodulation. 2020 Jun 1; 23 (4): 515-524.

BackgroundDeep brain stimulation (DBS) is a well-accepted treatment of Parkinson's disease (PD). Motor phenotypes include tremor-dominant (TD), akinesia-rigidity (AR), and postural instability gait disorder (PIGD). The mechanism of action in how DBS modulates motor symptom relief remains unknown.ObjectiveBlood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to determine whether the functional activity varies in response to DBS depending on PD phenotypes.Materials And MethodsSubjects underwent an fMRI scan with DBS cycling ON and OFF. The effects of DBS cycling on BOLD activation in each phenotype were documented through voxel-wise analysis. For each region of interest, ANOVAs were performed using T-values and covariate analyses were conducted. Further, a correlation analysis was performed comparing stimulation settings to T-values. Lastly, T-values of subjects with motor improvement were compared to those who worsened.ResultsAs a group, BOLD activation with DBS-ON resulted in activation in the motor thalamus (p < 0.01) and globus pallidus externa (p < 0.01). AR patients had more activation in the supplementary motor area (SMA) compared to PIGD (p < 0.01) and TD cohorts (p < 0.01). Further, the AR cohort had more activation in primary motor cortex (MI) compared to the TD cohort (p = 0.02). Implanted nuclei (p = 0.01) and phenotype (p = <0.01) affected activity in MI and phenotype alone affected SMA activity (p = <0.01). A positive correlation was seen between thalamic activation and pulse-width (p = 0.03) and between caudate and total electrical energy delivered (p = 0.04).ConclusionsThese data suggest that DBS modulates network activity differently based on patient motor phenotype. Improved understanding of these differences may further our knowledge about the mechanisms of DBS action on PD motor symptoms and to optimize treatment.© 2020 International Neuromodulation Society.

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