Objective: Determine whether therapeutic pallidal deep brain stimulation can entrain finely tuned gamma oscillations in the motor cortex.

Background: In Parkinson’s disease (PD),  finely tuned gamma oscillations (FTG) at 60-90 Hz (also called “narrowband gamma”) have been described in the human subthalamic nucleus (STN) and motor cortex, and may represent a “prokinetic” rhythm induced by levodopa and movement.  Recently, therapeutic subthalamic deep brain stimulation (DBS) was found to entrain motor cortical gamma oscillations at half stimulation frequency. We hypothesize that gamma entrainment is important to the mechanism of DBS in PD. Since clinical effects of subthalamic and pallidal stimulation are similar, we sought to determine if pallidal stimulation can also modulate cortical FTG.

Method: Three PD patients were implanted bilaterally with quadripolar electrode leads in globus pallidus (GP) and over the sensorimotor cortex, attached to bilateral investigational bidirectional (sense and stimulate) pulse generators (Summit RC+S, Medtronic). At home, on their normal schedule of antiparkinsonian medications and during normal activities, patients wirelessly streamed eight channels of field potentials, both before and during activation of therapeutic pallidal DBS. Time series data were divided into 30 second segments for calculation of power spectra and pallido-cortical coherence.

Results: In total, over 300 hours pre stimulation and post stimulation were collected. FTG were observed in the cortex and in pallido-cortical coherence, prior to stimulation in 5 of 6 hemispheres. These oscillations, fluctuated with medication cycle, and were most prominent in precentral compared to postcentral gyrus. Pallidal DBS entrained FTG at half stimulation frequency (65 Hz or 75 Hz) in 4 of 6 hemispheres, including one where FTG had not been observed prior to initiating stimulation.

Conclusion: Therapeutic pallidal stimulation entrains FTG in precentral gyrus, similar to subthalamic stimulation. This has several mechanistic implications: 1) Cortical gamma entrainment does not require a hyperdirect pathway (which connects cortex to STN but not GP). 2) Gamma entrainment may be an important mechanism of DBS in PD, since it has been associated with therapeutic stimulation at both of the main targets effective for rigid/akinetic PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pallidal-deep-brain-stimulation-entrains-finely-tuned-gamma-oscillations-in-motor-cortex/