Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease

Abstract

Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (ϳ3 and ϳ23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (ϳ3 ms) and medium (ϳ23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity.

Pallidal deep brain stimulation modulates cortical excitability and plasticity

“…DBS with clinical setting at high frequency did not cause paresthesia in any patient. 21,41,42 This is similar to the effects of pairing median nerve stimulation with motor cortical stimulation at suitable intervals, which leads to long-term potentiation-like effects, 21 whereas single-pulse stimulation leads to short-latency afferent inhibition of the motor cortex. 40 Therefore, the expected conduction time from GPi to cortex with direct activation of sensory fibers should be 2 to 6 milliseconds (as somatosensory evoked potential latency was 20 milliseconds recorded at the cortical level) and is much shorter than the cortical evoked potential latency (10 and 25 milliseconds) found in our study.…”

Hyperkinetic disorders and loss of synaptic downscaling

“…At present, however, there is still a gap in the knowledge on the reciprocal links between plastic changes occurring in the basal ganglia and aberrant plasticity observed in the cortex. In fact, while most electrophysiological studies on animal models of hyperkinetic disorders have focused on basal ganglia circuits, clinical electrophysiological studies using TMS mostly target cortical circuits (motor cortex) 58,99,100 . Although this gap should be filled in future studies, loss of downscaling in both cortical and subcortical structures might represent a common synaptic mechanism occurring in distinct hyperkinetic disorders, as detected using neurophysiological approaches (Fig.…”

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines

“…This effect may be amplified by the lower resistance of the burr hole if the transcra-nial electrode is closer than approximately 2 cm (Datta et al, 2010). Another concern could be the still unknown combined biological effects of tDCS with intracranial stimulation since both tDCS and DBS (Kim et al, 2015; Udupa et al, 2016) can induce cortical plasticity alterations.…”