A Single Mechanism for Global and Selective Response Inhibition under the Influence of Motor Preparation.

In our everyday behavior, we frequently cancel one movement while continuing others. Two competing models have been suggested for the cancellation of such specific actions: (1) the abrupt engagement of a unitary global inhibitory mechanism followed by reinitiation of the continuing actions; or (2) a balance between distinct global and selective inhibitory mechanisms. To evaluate these models, we examined behavioral and physiological markers of proactive control, motor preparation, and response inhibition using a combination of behavioral task performance measures, electromyography, electroencephalography, and motor evoked potentials elicited with transcranial magnetic stimulation. Healthy human participants of either sex performed two versions of a stop signal task with cues incorporating proactive control: a unimanual task involving the initiation and inhibition of a single response, and a bimanual task involving the selective stopping of one of two prepared responses. Stopping latencies, motor evoked potentials, and frontal ß power (13-20 Hz) did not differ between the unimanual and bimanual tasks. However, evidence for selective proactive control before stopping was manifest in the bimanual condition as changes in corticomotor excitability, µ (9-14 Hz), and ß (15-25 Hz) oscillations over sensorimotor cortex. Together, our results favor the recruitment of a single inhibitory stopping mechanism with the net behavioral output depending on the levels of action-specific motor preparation.SIGNIFICANCE STATEMENT Response inhibition is a core function of cognitive flexibility and movement control. Previous research has suggested separate mechanisms for selective and global inhibition, yet the evidence is inconclusive. Another line of research has examined the influence of preparation for action stopping, or what is called proactive control, on stopping performance, yet the neural mechanisms underlying this interaction are unknown. We combined transcranial magnetic stimulation, electroencephalography, electromyography, and behavioral measures to compare selective and global inhibition models and to investigate markers of proactive control. The results favor a single inhibitory mechanism over separate selective and global mechanisms but indicate a vital role for preceding motor activity in determining whether and which actions will be stopped.

Frontal-midline theta reflects different mechanisms associated with proactive and reactive control of inhibition.

Reactive control of response inhibition is associated with a right-lateralised cortical network, as well as frontal-midline theta (FM-theta) activity measured at the scalp. However, response inhibition is also governed by proactive control processes, and how such proactive control is reflected in FM-theta activity and associated neural source activity remains unclear. To investigate this, simultaneous recordings of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data was performed while participants performed a cued stop-signal task. The cues (0%, 25% or 66%) indicated the likelihood of an upcoming stop-signal in the following trial. Results indicated that participants adjusted their behaviour proactively, with increasing go-trial reaction times following increasing stop-signal probability, as well as modulations of both go-trial and stop-trial accuracies. Target-locked theta activity was higher in stop-trials than go-trials and modulated by probability. At the single-trial level, cue-locked theta was associated with shorter reaction-times, while target-locked theta was associated with both faster reaction times and higher probability of an unsuccessful stop-trial. This dissociation was also evident at the neural source level, where a joint ICA revealed independent components related to going, stopping and proactive preparation. Overall, the results indicate that FM-theta activity can be dissociated into several mechanisms associated with proactive control, response initiation and response inhibition processes. We propose that FM-theta activity reflects both heightened preparation of the motor control network, as well as stopping-related processes associated with a right lateralized cortical network.

The P300 as marker of inhibitory control - Fact or fiction?

Inhibitory control, i.e., the ability to stop or suppress actions, thoughts, or memories, represents a prevalent and popular concept in basic and clinical neuroscience as well as psychology. At the same time, it is notoriously difficult to study as successful inhibition is characterized by the absence of a continuously quantifiable direct behavioral marker. It has been suggested that the P3 latency, and here especially its onset latency, may serve as neurophysiological marker of inhibitory control as it correlates with the stop signal reaction time (SSRT). The SSRT estimates the average stopping latency, which itself is unobservable since no overt response is elicited in successful stop trials, based on differences in the distribution of go reaction times and the delay of the stop-relative to the go-signal in stop trials. In a meta-analysis and an independent electroencephalography (EEG) experiment, we found that correlations between the P3 latency and the SSRT are indeed replicable, but also unspecific. Not only does the SSRT also correlate with the N2 latency, but both P3 and N2 latency measures show similar or even higher correlations with other behavioral parameters such as the go reaction time or stopping accuracy. The missing specificity of P3-SSRT correlations, together with the general pattern of associations, suggests that these manifest effects are driven by underlying latent processes other than inhibition, such as behavioral adaptations in context of performance monitoring operations.

tDCS over the inferior frontal gyri and visual cortices did not improve response inhibition.

The ability to cancel an already initiated response is central to flexible behavior. While several different behavioral and neural markers have been suggested to quantify the latency of the stopping process, it remains unclear if they quantify the stopping process itself, or other supporting mechanisms such as visual and/or attentional processing. The present study sought to investigate the contributions of inhibitory and sensory processes to stopping latency markers by combining transcranial direct current stimulation (tDCS), electroencephalography (EEG) and electromyography (EMG) recordings in a within-participant design. Active and sham tDCS were applied over the inferior frontal gyri (IFG) and visual cortices (VC), combined with both online and offline EEG and EMG recordings. We found evidence that neither of the active tDCS condition affected stopping latencies relative to sham stimulation. Our results challenge previous findings suggesting that anodal tDCS over the IFG can reduce stopping latency and demonstrates the necessity of adequate control conditions in tDCS research. Additionally, while the different putative markers of stopping latency showed generally positive correlations with each other, they also showed substantial variation in the estimated latency of inhibition, making it unlikely that they all capture the same construct exclusively.

Strategy switches in proactive inhibitory control and their association with task-general and stopping-specific networks.

Prior information about the likelihood of a stop-signal pre-activates networks associated with response inhibition in both go- and stop-trials. How such prior information modulates the neural mechanisms enacting response inhibition is only poorly understood. To investigate this, a cued stop-signal task (with cues indicating stopping probabilities of 0%, 25% or 66%) was implemented in combination with functional magnetic resonance imaging (fMRI) data acquisition. Specifically, we focused on the effect of proactive inhibitory control as reflected in the activity of regions known to regulate response inhibition. Further, modulatory activity profiles in three different sub-regions of the right inferior frontal area were investigated. Behavioural results revealed an adaptation of task strategies through proactive control, with a possible gain for efficient inhibition at high stopping probabilities. The imaging data indicate that this adaption was supported by different regions traditionally involved in the stopping network. While the right inferior parietal cortex (IPC), right middle frontal gyrus (MFG), right inferior frontal gyrus (rIFG) pars triangularis, and left anterior insula all showed increased go-trial activity in the 0% condition compared to the 25% condition, the pre-supplementary motor area (pre-SMA), anterior midcingulate cortex (aMCC), right anterior insula, and the rIFG pars opercularis showed a more stopping-specific pattern, with stronger stop-trial activity in the 66% condition than in the 25% condition. Furthermore, activity in inferior frontal sub-regions correlated with behavioural changes, where more pronounced response slowing was associated with stronger activity increases from low to high stopping probabilities. Notably, the different right inferior frontal sub-regions showed different activity patterns in response to proactive inhibitory control modulations, supporting the idea of a functional dissociation within this area. Specifically, while the pars opercularis and the right insula showed stopping-related modulations of activity, the rIFG pars triangularis exhibited modulations only in go-trials with strong adaptions to fast responding or proactive slowing. Overall, the results indicate that proactive inhibitory control results in the switching of task or strategy modes, either favouring fast responding or stopping, and that these strategical adaptations are governed by an interplay of different regions of the stopping network.