We studied the time course and nature of interactions between the subthalamic nucleus (STN) and the motor cortex in 8 Parkinson disease (PD) patients with chronically implanted STN deep-brain stimulation (DBS) electrodes. We first identified the cortical evoked potentials following STN stimulation. The most consistent potential was positive wave with peak latency of 22.2 +/- 1.2 ms from stimulation of clinically effective contacts. We then stimulated the motor cortex with transcranial magnetic stimulation (TMS) at 2-15 ms and at the latency of the evoked potential ( approximately 23 ms) following STN DBS. TMS induced currents in 3 directions: lateral-medial (LM) direction activated corticospinal axons directly, posterior-anterior (PA), and anterior-posterior (AP) directions activated corticospinal neurons transynaptically. Motor-evoked potentials (MEP) elicited by AP and PA TMS were facilitated at short (2-4 ms) and medium latencies (21-24 ms). However, MEPs elicited by LM TMS were not modified by STN DBS. Short-latency antidromic stimulation of the corticosubthalamic projections and medium latency transmission likely through the basal ganglia-thalamocortical circuit led to cortical evoked potentials and increased motor cortex excitability at specific intervals following STN stimulation at clinically effective contacts. Cortical activation may be related to the clinical effects of STN DBS in PD.

Background Rapid action-stopping leads to global motor suppression. This is shown by studies using Transcranial Magnetic Stimulation to measure corticospinal excitability of task-unrelated effectors, e.g., from the hand during speech-stopping. We hypothesize this global suppression relates to the subthalamic nucleus of the basal ganglia. Several STN local field potential studies in Parkinson’s patients have shown increased ß-band power during successful stopping. Here, we aimed to test whether this STN ß-band activity indexes global motor suppression measured by transcranial magnetic stimulation. Methods We studied nine medicated PD patients (age: 47 – 67y, mean: 55.8; 3 female) who were implanted with STN-DBS electrodes. Participants performed a vocal stop-signal task (i.e., they had to occasionally stop a vocal response) while we simultaneously recorded local field potentials from right STN and delivered transcranial magnetic stimulation to primary motor cortex to measure corticospinal excitability from a task-unrelated hand muscle (first dorsal interosseous). Results Replicating prior results, STN ß-band power was increased (p < .005) and corticospinal excitability was reduced (p = .024) (global motor suppression) during successful stopping. As hypothesized, such global motor suppression was greater for successful stop-trials with higher STN ß-power (median-split: p = .043), which was further evident in a negative correlation between single-trial STN ß-power and corticospinal excitability (mean r = -.176, p = .011). Conclusion These findings link stopping-related global motor suppression to STN ß-band activity through simultaneous recordings of STN and corticospinal excitability. The results support models of basal ganglia that propose the STN has broad motor suppressive effects.

OBJECTIVEPhysicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients’ accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research.METHODSA phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from “the worst” to “the most common.”In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed.RESULTSIn the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event.CONCLUSIONSUnder the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

Objectives: The oscillation model of Parkinson disease (PD) states that, in the subthalamic nucleus (STN), increased (4-10 Hz) and ␤ (11-30 Hz) frequencies were associated with worsening whereas ␥ frequencies (31-100 Hz) were associated with improvement of motor symptoms. However, the peak STN frequency in each band varied widely from subject to subject. We hypothesized that STN deep brain stimulation (DBS) at individualized ␥ frequencies would improve whereas or ␤ frequencies would worsen PD motor signs. Methods:We prospectively studied 13 patients with PD. STN local field potential (LFP) was recorded after electrode implantations, in the OFF and then in ON dopaminergic medication states while patients performed wrist movements. Six individual peak frequencies of the STN LFP power spectra were obtained: the greatest decrease in and ␤ and greatest increase in ␥ frequencies in the ON state (MED) and during movements (MOVE). Eight DBS frequencies were applied including 6 MED and MOVE frequencies, high frequency (HF) used for chronic stimulation, and no stimulation. The patients were assessed using the motor Unified Parkinson's Disease Rating Scale (mUPDRS).Results: STN DBS at ␥ frequencies (MED and MOVE) and HF significantly improved mUPDRS scores compared to no stimulation and both ␥ frequencies were not different from HF. DBS at and ␤ frequencies did not worsen mUPDRS scores compared to no stimulation. Conclusion:Short-term administration of STN DBS at peak dopamine-dependent or movementrelated ␥ frequencies were as effective as HF for reducing parkinsonian motor signs but DBS at and ␤ frequencies did not worsen PD motor signs. Classification of evidence:This study provides Class III evidence that STN DBS at patient-specific ␥ frequencies and at usual high frequencies both improved mUPDRS scores compared to no stimulation and did not differ in effect. Neurology 1 Studies of oscillatory activities in the basal ganglia (BG) in patients with PD suggested that parkinsonian motor symptoms may be related to excessive pathologic oscillations in the BG in the low frequencies (Ͻ30 Hz).2,3 Increased (4 -10 Hz) frequencies in STN were associated with parkinsonian resting tremor. 4 Moreover, excessive ␤ (11-30 Hz) frequencies were recorded from the STN when patients with PD were withdrawn from their dopaminergic medications (OFF state) 5-7 and these frequencies were reduced when patients were in the on dopaminergic

Single-pulse DBS modulates cortical excitability and plasticity at specific time intervals. These effects may be related to the mechanism of action of DBS. Combination of DBS with cortical stimulation with appropriate timing has therapeutic potential and could be explored in the future as a method to enhance the effects of neuromodulation for neurological and psychiatric diseases. Ann Neurol 2018;83:352-362.

These results support the theory that the time of LFO increase recorded from the STN corresponds to a conflict-processing function. They also provide one of the first demonstrations of event-related DBS of the STN in humans during a cognitive control paradigm. Ann Neurol 2018;84:515-526.

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