Objective: To investigate whether motor cortical plasticity can be induced in Parkinson’s disease (PD) patients by pairing subthalamic deep brain stimulation (STN-DBS) and repetitive transcranial magnetic stimulation applied to the primary motor cortex (M1-rTMS).

Background: Cortical plasticity can be investigated using paired associative stimulation (PAS): a technique that involves repeatedly pairing stimulation of a brain region through two afferent inputs. PD patients have exhibited impaired motor cortical plasticity. Pairing STN-DBS with single-pulse M1-TMS at specific intervals at the traditional PAS pairing frequency of 0.1 Hz can induce transient long-term potentiation-like (LTP-like) effects in the motor cortex for up to 45 minutes. Here, we hypothesize that a 3 Hz pairing of STN-DBS and M1-rTMS (i.e., each time the stimuli are presented) will induce LTP-like effects in the motor cortex more efficiently.

Method: We tested PD patients with STN-DBS on dopaminergic medication. The protocol consisted of 600 pulses of M1-rTMS conditioned by STN-DBS at a 3 Hz pairing frequency with individualized inter-stimulus intervals (ISIs) based on optimally observed facilitation for each patient. We tested three ISI conditions: short (3-5 ms), medium (18-22 ms), and a control-interval of 167 ms, in separate randomized sessions. Cortical plasticity was assessed by comparing corticospinal excitability using single-pulse TMS and short-interval intracortical inhibition (SICI) using paired-pulse TMS. Post-stimulation measurements for cortical excitability and intracortical circuits were made in 20-minute intervals: 20 minutes (‘T20’), T40, and T60 minutes after stimulation.

Results: Preliminary results from 8 patients showed that short-interval DBS-TMS pairing increased motor evoked potential (MEP) amplitudes compared to baseline for up to T60. After medium-interval DBS-TMS pairing, there was a trend for decreased MEP amplitudes, and the control-interval did not change MEP amplitudes. SICI remained unchanged over time. Further subjects are being recruited and data analysis is ongoing.

Conclusion: These findings show that 5 minutes of pairing STN-DBS with M1-rTMS can produce prolonged LTP-like effects in the motor cortex for up to 60 minutes. These LTP-like effects were observed only at an ISI between 3-5 ms, presumably through the cortico-STN hyperdirect pathway.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/inducing-motor-cortical-plasticity-in-parkinsons-disease-patients-using-subthalamic-deep-brain-stimulation-and-repetitive-transcranial-magnetic-stimulation/