Motor Task-Dependent Dissociated Effects of Transcranial Random Noise Stimulation in a Finger-Tapping Task Versus a Go/No-Go Task on Corticospinal Excitability and Task Performance

Background and Objective: Transcranial random noise stimulation (tRNS) is an emerging non-invasive brain stimulation technique to modulate brain function, with previous studies highlighting its considerable benefits in therapeutic stimulation of the motor system. However, high variability of results and bidirectional task-dependent effects limit more widespread clinical application. Task dependency largely results from a lack of understanding of the interaction between externally applied tRNS and the endogenous state of neural activity during stimulation. Hence, the aim of this study was to investigate the task dependency of tRNS-induced neuromodulation in the motor system using a finger-tapping task (FT) versus a go/no-go task (GNG). We hypothesized that the tasks would modulate tRNS’ effects on corticospinal excitability (CSE) and task performance in opposite directions.Methods: Thirty healthy subjects received 10 min of tRNS of the dominant primary motor cortex in a double-blind, sham-controlled study design. tRNS was applied during two well-established tasks tied to diverging brain states. Accordingly, participants were randomly assigned to two equally-sized groups: the first group performed a simple motor training task (FT task), known primarily to increase CSE, while the second group performed an inhibitory control task (go/no-go task) associated with inhibition of CSE. To establish task-dependent effects of tRNS, CSE was evaluated prior to- and after stimulation with navigated transcranial magnetic stimulation.Results: In an ‘activating’ motor task, tRNS during FT significantly facilitated CSE. FT task performance improvements, shown by training-related reductions in intertap intervals and increased number of finger taps, were similar for both tRNS and sham stimulation. In an ‘inhibitory’ motor task, tRNS during GNG left CSE unchanged while inhibitory control was enhanced as shown by slowed reaction times and enhanced task accuracy during and after stimulation.Conclusion: We provide evidence that tRNS-induced neuromodulatory effects are task-dependent and that resulting enhancements are specific to the underlying task-dependent brain state. While mechanisms underlying this effect require further investigation, these findings highlight the potential of tRNS in enhancing task-dependent brain states to modulate human behavior

Context-dependent representation and control of simple finger movements through motor surround inhibition in the primary motor cortex

Hintergrund: Im zentralen Nervesnsystem (ZNS) des Menschen sind sowohl sensorisch gewonnene, afferente Informationen über die Außenwelt als auch motorische, efferente Programme zur Manipulation der Außenwelt repräsentiert. Die physiologischen Korrelate der Repräsentation des menschlichen Bewegungsrepertoires unterliegen einer räumlichen und zeitlichen Variabilität, die aus einer kontextabhängigen Aktivität der Organe des motorischen Systems des Menschen resultiert. Es ist Gegenstand aktueller Forschung zur motorischen Kontrolle durch das menschliche ZNS, inwieweit der primärmotorische Kortex (M1) bloß eine passive Somatotopie möglicher Bewegungen abbildet oder auch eine aktive Steuerungsfunktion in der Bildung motorischer Programme inne hat. Ich untersuchte mittels navigierter transkranieller Magnetstimulation (nTMS) während einer Reaktionszeitaufgabe die Hypothese, dass im Kontext eines motorischen Befehls, induziert durch Motor Imagery, M1 aktiv an der dynamischen Kodierung motorischer Repräsentationen einfacher Fingerbewegungen beteiligt ist. Die Hauptzielstellung war, in Abhängigkeit von Motor Imagery die integrierte motorische Aktivität, definiert als die Wechselwirkung zwischen der räumlichen und zeitlichen Struktur kortikospinaler Erregbarkeit (CSE) und subliminaler muskulärer Aktivität, zu untersuchen. Als zentralen Steuerungsmechanismus nahm ich Umgebungsinhibition in primärmotorischen kortikalen Netzwerken an. Methoden: Ich setzte ein visuelles Stimulationsparadigma ein, um durch Motor Imagery induzierte Variabilität in den Erregbarkeitsgipfeln („Hot Spots“) über primärmotorischen Projektionen zu drei definierten Handmuskeln herauszuarbeiten. Mittels einer Mehrebenenanalyse wertete ich wiederholte Stichproben innerhalb von zehn Probanden in Form eines balancierten 4 × 4 × 4-faktoriellen Designs aus. Eine methodische Vorstudie an weiteren zehn Probanden diente zur Etablierung eines validen Kontrollverfahrens für den Einfluss von Vorinnervation als physiologiche Störgröße auf motorisch evozierte Potenziale (MEPs) im Elektromyogramm (EMG). Ergebnisse: Magnetstimulation über einem fixen Referenzpunkt zeigte eine funktionelle Umstrukturierung der erregten neuronalen Netzwerke in M1 in Abhängigkeit von Motor Imagery innerhalb von 100 ms vor einer motorischen Antwort. Die Interaktion von peripherer EMG-Aktivität und Motor Imagery zeigte eine Modulation der Repräsentationen durch funktionelle Umgebungsinhibition. Während einer motorischen Aufgabe kann Vorinnervation per Partialisierung mittels einer multiplen linearen Regressionsanalyse suffizient kontrolliert werden. Diskussion: Die vorliegende Arbeit charakterisiert die neurophysiologischen Mechanismen der aktiven Steuerung einfacher Fingerbewegungen durch das Handareal von M1. Grundlage dieser Funktion ist die dynamische Aktivität in umschriebenen kortikospinalen Netzwerken von M1, die im Kontext einer aktuellen Bewegung spezifisch das kortikofugale Ausgangssignal zu den getesteten Kennmuskeln kodiert. Die Auswahl einer motorischen Repräsentation wird von motorischer Umgebungsinhibition begleitet, deren qualitative und quantitative Ausprägung als Maß primärmotorischer Funktion in zukünftigen Studien dienen kann.Background: Representations of movement in the human motor system are highly dynamic in time and structure. Changes in the physiological correlates of these representations reflect context-dependency of representing neuronal networks. The question to which extent the primary motor cortex (M1) actively engages in these dynamics and how it is embedded in the top-down stream of motor control has remained central to neurosciences in the past and present. In this study with navigated transcranial magnetic stimulation, I tested the main hypothesis that M1 dynamically shapes representations in the primary motor hand area by means of motor surround inhibition. Methods: To access motor representations, I employed a motor imagery paradigm implemented in a purely instructive simple reaction time task of mentally rehearsing brisk finger flexions at four pre-defined latencies either relative to a visual go cue or a subject’s expected response onset. Navigated transcranial magnetic stimulation guaranteed a controlled experimental intervention over a constant “hot spot” as a highly circumscribed referential target site in the dominant primary motor hand knob. For additional control of physiological variability, I established a valid control method for the correction of pre-innervation possibly confounding motor evoked potentials (MEPs). Results: I find that imagery of simple finger movements facilitates motor evoked potentials recorded from the corresponding target muscles within a 100 ms time bin prior to a response and independent of the initially mapped somatotopy in the primary motor hand area. Functionally unrelated muscles were inhibited proportionally to subliminal motor output accompanying imagery. During a motor task, confounding of MEPs can be diminished by partitioning pre-innervation using a multilinear regression analysis. Discussion: This study provides novel insight into mechanisms of context-dependent on-demand modulations of representations of simple finger movements in M1. Engangement of a motor representation is possibly stabilized by motor surround inhibition, which can serve as a measure of primary motor functioning in future studies

Evolution of premotor cortical excitability after cathodal inhibition of the primary motor cortex: a sham-controlled serial navigated TMS study.

BACKGROUND: Premotor 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). PURPOSE: The 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. HYPOTHESIS: Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability. METHODS: We 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. RESULTS: Cathodal tDCS successfully reduced M1 excitability and motor performance speed. PMC excitability was increased for longer and was the only significant predictor of motor performance. CONCLUSION: The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance

Diagram illustrating the randomization of parameters to be examined in one exemplary subject.

<p>Parameters of motor cortical excitability and function were assessed at two time intervals (early or late) following transcranial direct current stimulation (indicated by a flash symbol). Changes in measures recorded 0–40 minutes after discontinuation of the stimulation were considered to be due to early aftereffects. Changes recorded in the successive 40 minutes were considered to be due to late aftereffects. Aftereffects which occured in only one recording period were considered to be short-lasting; others were considered to be long-lasting. Immediately before and after tDCS, 20 stimuli were applied at a fixed intensity (see methods section for details) over M1 to examine tDCS-induced changes of corticospinal excitability. Afterwards, the five neurophysiological or functional parameters being evaluated were randomly assigned to one of four time slots in the overall 80-minute post-stimulation period. IO  =  input-output curve, TAP  =  finger-tapping, ICE  =  intracortical excitability (Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), IHI  =  interhemispheric inhibition, MT  =  motor threshold; Pos1 – Pos4: Random position in time for each parameter.</p

Summary of experimental results.

<p>ANOVA results have been categorized with respect to whether data was compared between brain <i>region</i>s (i.e. primary motor cortex (M1) and dorsal premotor cortex (PMC)) or <i>intervention</i>s (i.e. cathodal and sham stimulation) and whether they examine functional performance or electrophysiological properties. The test of MEP latency contains the two-level factor <i>muscle</i> for forearm and hand muscles. The two-level factor <i>time</i> distinguishes between early(<40 min) and late (>40 min) period aftereffects. The four-level factor <i>TMS intensity</i> refers to 10% increments of the individual resting motor threshold (RMT) used as stimulation intensities to assess input-output curves. Paired-pulse stimulation sequences contain the two-level factor ISI reflecting SICI and ICF protocols. Please refer to the methods section for further details. * p<0.05.</p

Input-output curves over PMC. MEP average amplitudes defined by stimulation at 110% through 140% RMT.

<p>In contrast to sham tDCS, cathodal tDCS significantly enhanced cortical excitability. Significant results were found at 130% (late period) and 140% (both periods) RMT. Error bars represent the standard error of the mean. * p<0.05</p

Results and comparison of electrophysiological responses to either cathodal or sham stimulation in the primary motor area.

<p>A) Cortical excitability estimates. MEP average amplitude in the early and later period. In contrast to sham tDCS, cathodal tDCS significantly diminished mean MEP amplitudes by about 50%. B) Input-output curves. MEP average amplitudes at 110% through 140% RMT. In contrast to sham tDCS, cathodal tDCS significantly diminished mean MEP amplitudes at stimulation strengths of 130% and 140% RMT. C) Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Average amplitudes of the test MEP at 2 and 5 ms ISI. SICI is enhanced in the early and significantly reduced in the late post-stimulation period after cathodal stimulation. ICF is not significantly affected by the cathodal stimulation. The time periods in all figures correspond to the definition of time intervals in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057425#pone-0057425-g001" target="_blank">Figure 1</a>. Error bars represent the standard error of the mean. * p<0.05</p

Maximum finger-tapping frequency reached in 30 seconds before and after 40 minutes (see Figure 1).

<p>Error bars represent the standard error of the mean. Finger-tapping speed is significantly slowed directly after cathodal stimulation as compared to sham stimulation or the late period. * p<0.05</p