Individual differences in intracortical inhibition during behavioural inhibition

doi:10.1016/j.neuropsychologia.2019.01.008

Neuropsychologia

Volume 124, 18 February 2019, Pages 55-65

https://doi.org/10.1016/j.neuropsychologia.2019.01.008 Get rights and content

Highlights

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Primary motor cortex (M1) inhibition was measured during a stop signal task
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Fast stoppers modulated M1 inhibition in accordance with responding and stopping
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Slow stoppers showed reduced M1 inhibition during both stopping and responding
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Inhibitory activity in M1 may explain individual differences in stopping ability

Abstract

The time required to abort an initiated response can be measured as the Stop Signal Reaction Time (SSRT). We determined whether GABAergic activity in the primary motor cortex (M1), measured using paired-pulse Transcranial Magnetic Stimulation (TMS) was related to SSRT. GABAergic activity in M1 was assessed by measuring Short-Interval Intracortical Inhibition (SICI). In two experiments, participants (males and females) completed the Stop Signal Task while we measured SICI from the first dorsal interosseous muscle. In Experiment 1, SICI was measured at fixed time points after Stop signal onset on Stop trials (50ms, 100ms, 150ms, 200ms), and at corresponding time points for Go trials. In Experiment 2 SICI was measured at fixed time points before the end of the SSRT interval (125ms, 75ms, 25ms) on Stop trials, and at corresponding time points for Go trials. In each experiment, 30 participants were classified as fast stoppers or slow stoppers based on a median split of their SSRTs. Fast stoppers had more SICI than slow stoppers, both when executing a response (Go trials) and when inhibiting a response (Stop trials). Indeed, the correlation between mean SICI and SSRT on successful Stop trials was 0.81. Experiment 2 showed that for fast stoppers (relative to baseline) there was reduced SICI on Go trials and recovery of SICI on Stop trials. Slow stoppers however, showed reduced SICI on Stop and Go trials relative to baseline. Our results show that individuals who are faster at stopping not only show more GABAergic activity in M1, but can more effectively control M1 GABAergic activity to inhibit motor cortical excitability when stopping a response and disinhibit excitability when executing a response.

Section snippets

Individual differences in intracortical inhibition during behavioural inhibition

An important aspect of our daily lives is our ability to abort an action after it has been initiated e.g. when a pedestrian must pull back from crossing the road on a green light if a passing car has failed to stop. Individuals vary greatly in the time it takes to stop an initiated response, as has been shown using the Stop Signal Task (Logan and Cowan, 1984), which estimates a subject's Stop Signal Reaction Time (SSRT). Slower SSRTs have been observed in clinical populations including

Participants

In Experiment 1, there were 30 participants (7 males, 29 right handed identified through self-report) in the final data set, with a mean age of 20.5 years (SD = 4.5). Participants were 26 undergraduate students and four postgraduate students from the University of Sydney, School of Psychology, one of which was the primary author, the only instance where another experienced experimenter conducted the session. We did not anticipate any biases on MEP and behavioural parameters with the first

Experiment 1 results

The aim of Experiment 1 was to determine whether fast and slow stoppers showed different levels of SICI at four time points relative to the onset of a stop signal: 50 ms, 100 ms, 150 ms and 200 ms. Participants were grouped as fast and slow stoppers based on a median split of the SSRTs from an initial calibration phase.

Discussion

We tested whether differences in SSRT were related to GABAergic activity in M1 during the stopping of a response. In two experiments, during response execution and inhibition, SICI was higher in individuals who were more efficient at stopping a response than those less efficient at stopping. Although Experiment 2 showed that slower stoppers showed evidence of inhibition at baseline (albeit weaker than faster stoppers), they showed little to no inhibitory response to ppTMS across the interval

Conclusion

Overall, we report an important finding of a relationship between GABAergic inhibitory activity in M1, measured as SICI, and the ability to stop an initiated response. This relationship was found during the inhibition of a response, building on our previous study (Chowdhury et al., 2018) where SICI was measured at rest. These results extend our understanding of the biological bases of behavioural control, and have important implications for approaches to investigate behavioural conditions that

Conflict of interest

None

Funding

This research was funded by a Discovery Project Grant DP160102871, from the Australian Research Council.

References (55)

R. Badry et al.
Suppression of human cortico-motoneuronal excitability during the Stop-signal task
Clin. Neurophysiol.
(2009)
W. Cai et al.
Stopping speech suppresses the task-irrelevant hand
Brain Lang.
(2012)
W.H. Chang et al.
Optimal number of pulses as outcome measures of neuronavigated transcranial magnetic stimulation
Clin. Neurophysiol.
(2016)
N.S. Chowdhury et al.
Variations in response control within At-Risk Gamblers and Healthy Controls explained by GABAergic activity in the motor cortex
Cortex
(2018)
M.R. Goldsworthy et al.
Minimum number of trials required for within- and between-session reliability of TMS measures of corticospinal excitability
Neuroscience
(2016)
B.D. Greenberg et al.
Decreased neuronal inhibition in cerebral cortex in obsessive-compulsive disorder on transcranial magnetic stimulation
Lancet
(1998)
A.M. Hermsen et al.
Test–retest reliability of single and paired pulse transcranial magnetic stimulation parameters in healthy subjects
J. Neurol. Sci.
(2016)
S. Ngomo et al.
Comparison of transcranial magnetic stimulation measures obtained at rest and under active conditions and their reliability
J. Neurosci. Methods
(2012)
I. Obeso et al.
Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition
Brain Stimul.
(2017)
G.M. Opie et al.
Modulation of short-and long-interval intracortical inhibition with increasing motor evoked potential amplitude in a human hand muscle
Clin. Neurophysiol.
(2014)

M. Orth et al.

The variability of intracortical inhibition and facilitation

Clin. Neurophysiol.

(2003)

S.H. Peurala et al.

Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF)

Clin. Neurophysiol.

(2008)

B.J. Poole et al.

Motor-evoked potentials reveal functional differences between dominant and non-dominant motor cortices during response preparation

Cortex

(2018)

S. Rossi et al.

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research

Clin. Neurophysiol.

(2009)

C.M. Stinear et al.

Primary motor cortex and movement prevention: where stop meets go

Neurosci. Biobehav. Rev.

(2009)

J. Valls-Solé et al.

Human motor evoked responses to paired transcranial magnetic stimuli

Electroencephalogr. Clin. Neurophysiol./Evoked Potentials Sect.

(1992)

F. Verbruggen et al.

Models of response inhibition in the stop-signal and stop-change paradigms

Neurosci. Biobehav. Rev.

(2009)

S.W. Wu et al.

Transcranial magnetic stimulation measures in attention-deficit/hyperactivity disorder

Pediatr. Neurol.

(2012)

A.R. Aron

The neural basis of inhibition in cognitive control

Neuroscientist

(2007)

M. Biabani et al.

The effects of transcranial direct current stimulation on short-interval intracortical inhibition and intracortical facilitation: a systematic review and meta-analysis

Rev. Neurosci.

(2018)

B. Boroojerdi et al.

Reproducibility of intracortical inhibition and facilitation using the paired‐pulse paradigm

Muscle Nerve

(2000)

H.H. Chao et al.

Activation of the pre-supplementary motor area but not inferior prefrontal cortex in association with short stop signal reaction time–an intra-subject analysis

BMC Neurosci.

(2009)

Y.C. Chiu et al.

Response suppression by automatic retrieval of stimulus–stop association: evidence from transcranial magnetic stimulation

J. Cogn. Neurosci.

(2012)

N.S. Chowdhury et al.

Pathological gambling and motor impulsivity: a systematic review with meta-analysis

J. Gambl. Stud.

(2017)

J. Cirillo et al.

Response inhibition activates distinct motor cortical inhibitory processes

J. Neurophysiol.

(2017)

J.P. Coxon et al.

Intracortical inhibition during volitional inhibition of prepared action

J. Neurophysiol.

(2006)

X. Du et al.

Individualized brain inhibition and excitation profile in response to paired pulse TMS

J. Mot. Behav.

(2014)

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The phasic cardiovascular activity influences the central nervous system through the systolic baroreceptor inputs, inducing widespread inhibitory effects on behavior. Through transcranial magnetic stimulation (TMS) delivered during resting-state over the left primary motor cortex and across the different cardiac phases, we measured corticospinal excitability (CSE) and distinct indices of intracortical motor inhibition: short (SICI) and long (LICI) interval, corresponding to GABA_A and GABA_B neurotransmission, respectively. We found a significant effect of the cardiac phase on short-intracortical inhibition, without any influence on LICI. Specifically, SICI was stronger at systole compared to diastole. These results show a tight relationship between the cardiac cycle and the inhibitory neurotransmission within M1, and in particular with GABA_A-ergic-mediated motor inhibition. We hypothesize that this process requires greater motor control via the gating mechanism and that this, in turn, needs to be recalibrated through the modulation of intracortical inhibition.
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Motor functions and cognitive processes are closely associated with each other. In humans, this linkage is reflected in motor system state changes both when an action must be prepared and stopped. Single-pulse transcranial magnetic stimulation showed that both action preparation and action stopping are accompanied by a reduction of corticospinal excitability, referred to as preparatory and response inhibition, respectively. While previous efforts have been made to describe both phenomena extensively, an updated and comprehensive comparison of the two phenomena is lacking. To ameliorate such deficit, this review focuses on the role and interpretation of single-coil (single-pulse and paired-pulse) and dual-coil TMS outcome measures during action preparation and action stopping in humans. To that effect, it aims to identify commonalities and differences, detailing how TMS-based outcome measures are affected by states, traits, and psychopathologies in both processes. Eventually, findings will be compared, and open questions will be addressed to aid future research.
On the (un)reliability of common behavioral and electrophysiological measures from the stop signal task: Measures of inhibition lack stability over time
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Response inhibition, the intentional stopping of planned or initiated actions, is often considered a key facet of control, impulsivity, and self-regulation. The stop signal task is argued to be the purest inhibition task we have, and it is thus central to much work investigating the role of inhibition in areas like development and psychopathology. Most of this work quantifies stopping behavior by calculating the stop signal reaction time as a measure of individual stopping latency. Individual difference studies aiming to investigate why and how stopping latencies differ between people often do this under the assumption that the stop signal reaction time indexes a stable, dispositional trait. However, empirical support for this assumption is lacking, as common measures of inhibition and control tend to show low test-retest reliability and thus appear unstable over time. The reasons for this could be methodological, where low stability is driven by measurement noise, or substantive, where low stability is driven by a larger influence of state-like and situational factors. To investigate this, we characterized the split-half and test-retest reliability of a range of common behavioral and electrophysiological measures derived from the stop signal task. Across three independent studies, different measurement modalities, and a systematic review of the literature, we found a pattern of low temporal stability for inhibition measures and higher stability for measures of manifest behavior and non-inhibitory processing. This pattern could not be explained by measurement noise and low internal consistency. Consequently, response inhibition appears to have mostly state-like and situational determinants, and there is little support for the validity of conceptualizing common inhibition measures as reflecting stable traits.
Is cortical inhibition in primary motor cortex related to executive control?
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Recent research using paired-pulse transcranial magnetic stimulation (TMS) has shown that the speed with which people can stop an action is linked to GABAergic inhibitory activity in the motor system. Specifically, a significant proportion of the variance in stop signal reaction time (SSRT; a widely used measure of inhibitory control) is accounted for by short-interval cortical inhibition (SICI). It is still unclear whether this relationship reflects a broader link between GABAergic processes and executive functions, or a specific link between GABAergic processes and motor stopping ability. The current study sought to replicate the correlation between SSRT and SICI while investigating whether this association generalises to other measures of inhibitory control and working memory, and to long-interval cortical inhibition (LICI). Participants completed a battery of inhibition (Stop-Signal, Stroop, Flanker) and working memory (n-back, Digit Span, and Operation Span) tasks. We replicated the correlation between SICI and SSRT but found no other correlations between behavioural measures of executive control and the two cortical measures of inhibition. These findings indicate that the relationship between SSRT and SICI is specific to a particular property of response inhibition and likely reflects the function of local inhibitory networks mediated by GABA_A.
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Response inhibition is our ability to suppress or cancel actions when required. Deficits in response inhibition are linked with a range of psychopathological disorders including addiction and OCD. Studies on response inhibition have largely focused on reactive inhibition—stopping an action when explicitly cued. Less work has examined proactive inhibition—preparation to stop ahead of time. In the current experiment, we studied both reactive and proactive inhibition by adopting a two-step continuous performance task (e.g., “AX”-CPT) often used to study cognitive control. By combining a dot pattern expectancy (DPX) version of this task with transcranial magnetic stimulation (TMS), we mapped changes in reactive and proactive inhibition within the motor system. Measured using motor-evoked potentials, we found modulation of corticospinal excitability at critical timepoints during the DPX when participants were preparing in advance to inhibit a response (at step 1: during the cue) and while inhibiting a response (at step 2: during the probe). Notably, motor system activity during early timepoints was predicted by a behavioural index of proactive capacity and could predict whether participants would later successfully inhibit their response. Our findings demonstrate that combining TMS with a two-step CPT such as the DPX can be useful for studying reactive and proactive inhibition, and reveal that successful inhibition is determined earlier than previously thought.
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Citation Excerpt :
We suggest SSRT should be considered with caution when used as the only measurement of stopping – i.e., in the absence of neurophysiological measurements. Furthermore, because SSRT is directly related to RT (Huster et al., 2020), it might be preferable to directly relate neural signatures of inhibition with neural signatures of going (Wessel, 2018; Nguyen et al., 2019) or to signatures of physiological inhibition (Chowdhury et al., 2019a, 2019b, 2020; Hynd et al., 2021). If this two-stage account of stopping is accurate, researchers should take these limitations of SSRT as a measure of stopping into account when designing SST studies and interpreting results.
The ability to stop already-initiated actions is a key cognitive control ability. Recent work on human action-stopping has been dominated by two controversial debates. First, the contributions (and neural signatures) of attentional orienting and motor inhibition after stop-signals are near-impossible to disentangle. Second, the timing of purportedly inhibitory (neuro)physiological activity after stop-signals has called into question which neural signatures reflect processes that actually contribute to action-stopping. Here, we propose that a two-stage model of action-stopping – proposed by Schmidt and Berke (2017) based on subcortical rodent recordings – may resolve these controversies. Translating this model to humans, we first argue that attentional orienting and motor inhibition are inseparable because orienting to salient events like stop-signals automatically invokes broad motor inhibition, reflecting a fast-acting, ubiquitous Pause process. We then argue that inhibitory signatures after stop-signals differ in latency because they map onto two sequential stages: the salience-related Pause and a slower, stop-specific Cancel process. We formulate the model, discuss recent supporting evidence in humans, and interpret existing data within its context.

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View full text

Individual differences in intracortical inhibition during behavioural inhibition

Highlights

Abstract

Section snippets

Individual differences in intracortical inhibition during behavioural inhibition

Participants

Experiment 1 results

Discussion

Conclusion

Conflict of interest

Funding

Clin. Neurophysiol.

Brain Lang.

Clin. Neurophysiol.

Cortex

Neuroscience

Lancet

J. Neurol. Sci.

J. Neurosci. Methods

Brain Stimul.

Clin. Neurophysiol.

Clin. Neurophysiol.

Clin. Neurophysiol.

Cortex

Clin. Neurophysiol.

Neurosci. Biobehav. Rev.

Electroencephalogr. Clin. Neurophysiol./Evoked Potentials Sect.

Neurosci. Biobehav. Rev.

Pediatr. Neurol.

The neural basis of inhibition in cognitive control

Neuroscientist

The effects of transcranial direct current stimulation on short-interval intracortical inhibition and intracortical facilitation: a systematic review and meta-analysis

Rev. Neurosci.

Reproducibility of intracortical inhibition and facilitation using the paired‐pulse paradigm

Muscle Nerve

Activation of the pre-supplementary motor area but not inferior prefrontal cortex in association with short stop signal reaction time–an intra-subject analysis

BMC Neurosci.

Response suppression by automatic retrieval of stimulus–stop association: evidence from transcranial magnetic stimulation

J. Cogn. Neurosci.

Pathological gambling and motor impulsivity: a systematic review with meta-analysis

J. Gambl. Stud.

Response inhibition activates distinct motor cortical inhibitory processes

J. Neurophysiol.

Intracortical inhibition during volitional inhibition of prepared action

J. Neurophysiol.

Individualized brain inhibition and excitation profile in response to paired pulse TMS

J. Mot. Behav.