The dorsal medial frontal cortex mediates automatic motor inhibition in uncertain contexts: evidence from combined fMRI and EEG studies

Abstract

Response inhibition is commonly thought to rely on voluntary, reactive, selective, and relatively slow prefrontal mechanisms. In contrast, we suggest here that response inhibition is achieved automatically, nonselectively, within very short delays in uncertain environments. We modified a classical go/nogo protocol to probe context-dependent inhibitory mechanisms. Because no single neuroimaging method can definitely disentangle neural excitation and inhibition, we combined fMRI and EEG recordings in healthy humans. Any stimulus (go or nogo) presented in an uncertain context requiring action restraint was found to evoke activity changes in the supplementary motor complex (SMC) with respect to a control condition in which no response inhibition was required. These changes included: (1) An increase in event-related BOLD activity, (2) an attenuation of the early (170 ms) event related potential generated by a single, consistent source isolated by advanced blind source separation, and (3) an increase in the evoked-EEG Alpha power of this source. Considered together, these results suggest that the BOLD signal evoked by any stimulus in the SMC when the situation is unpredictable can be driven by automatic, nonselective, context-dependent inhibitory activities. This finding reveals the paradoxical mechanisms by which voluntary control of action may be achieved. The ability to provide controlled responses in unpredictable environments would require setting-up the automatic self-inhibitory circuitry within the SMC. Conversely, enabling automatic behavior when the environment becomes predictable would require top-down control to deactivate anticipatorily and temporarily the inhibitory set.

Keywords: Alpha oscillations; EEG; automaticity; executive control; fMRI; go/nogo; response inhibition; task setting.

Figure 1

Protocol (A), models' predictions (B), and behavioral results (C). (A) Subjects were asked to react as fast as possible to a go stimulus (diamond) by means of a button press with the right thumb, and to withhold responses to an equiprobable nogo stimulus (X). In a control condition requiring no hypothetical inhibitory setting, only go stimuli were presented (go_control). In classical go/nogo tasks, go and nogo signals are scrambled within the same block of trials (standard mixed block design), assuming classically that inhibition is triggered by the nogo but not by the go stimulus. In contrast, an alternative view suggests that both stimuli induce automatic response inhibition in order to prevent premature responding. In other words, the usual nogo vs. go contrast would be incomplete to evidence all response inhibition mechanisms. To this aim, a control condition in which response inhibition is definitely not involved would be necessary (go trials for which subjects know in advance that there is no need to refrain from reacting). In the present experiment, this control condition was set by manipulating the color of the central fixation point (FP) of the display. A green FP indicated that not any nogo stimulus would be presented, enabling subjects to react automatically to any upcoming event (go_control condition). Conversely, a red FP was not informative of the identity of the upcoming target. (B) Strong, specific, predictions are attached to each hypothesis. The late, selective, account predicts that stimuli that have to be withheld (nogo) should induce specific brain activations with respect to stimuli that require a motor response (go). Conversely, the early, nonselective, account predicts that all stimuli presented in a context of uncertainty (both nogo and go) should induce inhibition‐related brain activations with respect to stimuli presented in a predictable environment (go_control). At the behavioral level, the standard model does not predict RT differences between go and go_control conditions. Conversely, the alternative model predicts that inhibition of automatic responses to any visual stimulus should lengthen RT in the red FP with respect to the green FP condition [e.g., Criaud et al., 2012]. (C) Normalized RT for go and go_control trials, pooled for all subjects. Distributions are best fitted by ex‐Gaussian functions. The RT difference between go and go_control trials reflects the effect of fast automatic response inhibition, a prerequisite for giving appropriate slow volitional response. Consistent with recent investigations using comparable methods and providing similar data and conclusions [Chiu and Aron, 2014], this major behavioral result fits the predictions of the automatic, nonselective, account of response inhibition.

Figure 2

(A) Topographic mapping of dMF170 activity at peak time, back‐projected on the scalp after source separation (upper left side), as compared with topographic mapping of all mixed components before source separation (upper right side). Time‐series of the net activity at C23 are presented for each condition (lower part; red: dMF170; blue: overall activity). The whole topography is strongly influenced by powerful visual activity around 170 ms to the extent that the dMF170 component remains invisible without filtering all interferent sources by means of advanced source separation. (B) Source localization of the dMF170 component with sLoreta. The probability map is presented on the MNI atlas. It extends across the SMC. Combined fMRI results are superimposed. BOLD imaging reveals an overlapping region that is more activated by the stimulus when the situation requires response inhibition (go and nogo conditions pooled together for analysis) than when it does not (go_control condition).

Figure 3

Psychophysiological characteristics of the dMF170 component. (A) Cumulated distributions of RT (go and go_control trials merged for analysis). Data are Vincentized with unequal‐sized subsets to compensate for RT distribution inhomogeneity in order to better assess what accounts for these differences in RT (quantiles are displayed with color code). (B) Time series of dMF170 activity (back‐projected on electrode C23/Fcz) (t0 = target presentation). The component peaks negatively approximately 170 ms after stimulus presentation, identically for go and nogo trials (means), but shows larger amplitude for the go_control condition. The mean evoked potential is displayed for each quantile. (C) The mean evoked potential for each quantile is referred to the corresponding mean RT. The amplitude of the dMF170 closely predicts RT. (D) Fast Fourier transform of the dMF170 ERP.

Figure 4

Spectral analyses of the “dMF170” component. (A) Mean evoked activity within each frequency band of interest (power is normalized with respect to the prestimulus period). Only delta/theta and Alpha bands show evoked activity. (B) Single‐trial modulations in spectral power within each frequency band of interest. Trials are sorted according to RT (black line). Only the Alpha band shows power evoked modulations consistent with the BOLD increase observed within the same region (more powerful evoked activity for longer RT). Correlation analysis shows that the higher the Alpha power at peak time, the smaller the amplitude of the dMF170. In contrast, the delta/theta band shows less powerful evoked activity for longer RT, reflecting possibly the evoked excitatory activity driving SMC efference (more powerful evoked activity for shorter RT, i.e., for noninhibited responses). No activity evoked by the stimulus is observed in upper frequency bands.