Evolution of Premotor Cortical Excitability after Cathodal Inhibition of the Primary Motor Cortex: A Sham-Controlled Serial Navigated TMS Study

Abstract

BackgroundPremotor cortical regions (PMC) play an important role in the orchestration of motor function, yet their role in compensatory mechanisms in a disturbed motor system is largely unclear. Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex (M1). Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion. Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1. These studies have contributed to our understanding of how M1 responds to changes in PMC neural activity. Yet, the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear. Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation (tDCS).PurposeThe primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance.HypothesisCathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability.MethodsWe enrolled 16 healthy participants in this randomized, double-blind, sham-controlled, crossover design study. All participants underwent navigated transcranial magnetic stimulation (nTMS) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical, intracortical and interhemispheric excitability. Cortical M1 excitability was inhibited using cathodal tDCS. Finger-tapping speeds were used to examine motor function.ResultsCathodal tDCS successfully reduced M1 excitability and motor performance speed. PMC excitability was increased for longer and was the only significant predictor of motor performance.ConclusionThe PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance.

Low-Frequency Repetitive Transcranial Magnetic Stimulation Targeted to Premotor Cortex Followed by Primary Motor Cortex Modulates Excitability Differently Than Premotor Cortex or Primary Motor Cortex Stimulation Alone

“…Although 80% of RMT was reported as the optimal conditioning intensity for SICI and ICF , this optimal value may be differentially modulated based upon in the specific rTMS parameters. As demonstrated by previous studies, both ISI and conditioning intensity significantly affect the responses of SICI and ICF . Following low‐frequency rTMS, some subjects may respond with inhibited responses while others are facilitated to the same test .…”

“…The differences between outcome excitability assessment measures (SICI, ICF, and CSP) in response to low‐frequency rTMS may be due to the different cortical inhibitory mechanisms measured and the sensitivity of each outcome, which has been reported to be interrelated . The LTD‐like effect induced by low‐frequency rTMS with the present parameters might affect these three mechanisms differentially , suggesting that CSP is the most sensitive to the modulations performed, but other modulations may affect other measures differently. One consideration regarding the paired‐pulse assessments is that the ISIs and conditioning pulse intensity of SICI and ICF were not optimized for individual participants.…”

“…However, M1 is still receiving excitatory projections from PMC, which may mitigate some of the inhibitory effects due to rTMS. Furthermore, recent evidence suggests this excitatory projection may be facilitated as a compensatory effect when M1 is inhibited . During the combined PMC + M1 stimulation, PMC excitatory projections may be initially weakened by rTMS targeted over PMC.…”

Increasing human leg motor cortex excitability by transcranial high frequency random noise stimulation

“…Baudewig et al, 2001;Kim et al, 2012;Lang et al, 2005;Polania et al, 2011)). On this line, it was recently observed that the downregulation of cortical excitability in the hand M1 increased the excitability in the ipsilateral premotor cortex (Schmidt et al, 2013). Therefore, we cannot exclude the possibility that by applying the stimulation over the leg M1 the supplementary and premotor areas were also indirectly stimulated.…”

Directed connectivity between primary and premotor areas underlying ankle force control in young and older adults

“…The PMC has been previously highlighted as a key region for adaptive processes in the motor system, particularly in the case of reduced M1 function. Behaviorally meaningful adaptations have been demonstrated in PMC after M1 lesions in animals and humans (62) and non-invasive brain stimulation suppressing M1 excitability (63), indicating that functional compensation may depend on PMC activity. Further, other studies have demonstrated age-related increases in PMC activation during motor tasks (5,9,64), and some of this work has additionally suggested that this activation may become increasingly useful with aging (64).…”