The Nature and Time Course of Cortical Activation Following Subthalamic Stimulation in Parkinson's Disease

Abstract

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.

Neuromuscular correlates of subthalamic stimulation and upper limb freezing in Parkinson’s disease

“…Another interesting aspect is the long-range synchronization of cortex and muscle at the individual tapping frequency itself. Our data show that cortical synchronization with the spinal agonist motor neurons is increased at tapping frequency with StimOn compared to StimOff and this adds to previous findings on increased corticospinal contributions resulting from subthalamic stimulation Kuriakose et al, 2010;Salenius et al, 2002;Weiss et al, 2012). To summarize, we identified two distinct network processes that parallel motor impairment in the PD 'off state': (i) decrease of corticomuscular synchrony at individual tapping frequency, and (ii) emergence of intermuscular synchronization around 8 Hz without coupling to the cortex.…”

“…As such, subthalamic neurostimulation modulated cortical activity in terms of movement-related desynchronization (Devos et al, 2004;Weiss et al, 2015). Moreover, STN-DBS increased motor cortex excitability (Kuriakose et al, 2010). Similarly, there is evidence for both defective corticospinal interactions and muscle activation at abnormally low frequencies <10 Hz in the clinical 'off' state (Salenius et al, 2002;Weiss et al, 2012).…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…STN stimulation has also been found to influence directly cortical neurons via antidromic activation of the corticosubthalamic pathway [298][299][300][301]. In fact, optogenetic studies in rodents have suggested that the antidromic activation of motor cortical input may be responsible for the clinical effects of STN DBS [299,302].…”

“…In fact, optogenetic studies in rodents have suggested that the antidromic activation of motor cortical input may be responsible for the clinical effects of STN DBS [299,302]. While antidromic stimulation of cortex has also been shown in nonhuman primates and in patients, based on short-latency cortical-evoked potentials [298,301,[303][304][305], it is not clear what role they play in the overall behavioral response to STN DBS in patients with movement disorders. Antidromic effects are not likely to play a prominent role in the case of GPi DBS [297,298], which achieves the same motor result as STN DBS.…”

Transcranial Magnetic Stimulation Treatment for Motor Symptoms in Parkinson’s Disease: A Review of Two Decades of Studies

“…All adverse events attributed to rTMS were minor and no studies reported the need for medical care in response an event: given the low rate of occurrence and the transient nature of the events, the authors concluded that rTMS does not carry significant risk of adverse events in the PD population. Moreover, TMS has also been used in patients with DBS implants: of 15 studies [73][74][75][76][77][78][79][80][81][82][83][84][85][86][87], only three [73,75,76] employed rTMS, while all the other employed single pulse TMS paradigms. No adverse events were reported in all 122 patients, so that preliminary evidence suggests that rTMS do not carry significant risk in this population [72].…”