A psychophysiological analysis of inhibitory motor control in the stop-signal paradigm.

We examined two potential inhibitory mechanisms for stopping a motor response. Participants performed a standard visual two-choice task in which visual stop signals and no-go signals were presented on a small proportion of the trials. Psychophysiological measures were taken during task performance to examine the time course of response activation and inhibition. The results were consistent with a horse race model previously proposed to account for data obtained using a stop-signal paradigm. The pattern of psychophysiological responses was similar on stop-signal and no-go trials suggesting that the same mechanism may initiate inhibitory control in both situations. We found a distinct frontal brain wave suggesting that inhibitory motor control is instigated from the frontal cortex. The results are best explained in terms of a single, centrally located inhibition mechanism. Results are discussed in terms of current neurophysiological knowledge.     

Levodopa medication does not influence motor inhibition or conflict resolution in a conditional stop-signal task in Parkinson’s disease

Evidence from animal, clinical, and imaging studies suggests that the basal ganglia and their frontal connections mediate motor inhibition, but the role of dopamine remains unclear. The aim of our study was to investigate, for the first time, whether levodopa medication influences motor inhibition and conflict resolution on the conditional stop-signal reaction time task in patients with Parkinson’s disease (PD) tested on or off their medication. Sixteen PD patients and 17 healthy controls performed the conditional stop-signal reaction time (SSRT) task, which requires inhibition of responses when a stop signal is presented on “critical” trials. Additionally, on “non-critical” trials, participants are instructed to ignore the stop signal and respond, thus generating conflict between motor inhibition and initiation; and conflict-induced slowing (CIS) on these “non-critical” trials. Levodopa medication did not significantly influence response initiation, inhibition (SSRT) or the measure of conflict resolution (CIS). Compared to healthy controls, PD patients showed significantly worse response initiation and inhibition both on and off their levodopa medication. Our results suggest that motor inhibition or conflict-induced slowing on the conditional stop-signal RT task are not altered by dopamine replacement in PD. This conclusion is consistent with evidence from animal studies and clinical pharmacological investigations suggesting a role for noradrenaline in motor inhibition and impulsivity.     

Visual-tactile saccadic inhibition

In an eye movement countermanding paradigm it is demonstrated for the first time that a tactile stimulus can be an effective stop signal when human participants are to inhibit saccades to a visual target. Estimated stop signal processing times were 90-140 ms, comparable to results with auditory stop signals, but shorter than those commonly found for manual responses. Two of the three participants significantly slowed their reactions in expectation of the stop signal as revealed by a control experiment without stop signals. All participants produced slower responses in the shortest stop signal delay condition than predicted by the race model (Logan and Cowan 1984) along with hypometric saccades on stop failure trials, suggesting that the race model may need to be elaborated to include some component of interaction of stop and go signal processing.     

It's not too late: The onset of the frontocentral P3 indexes successful response inhibition in the stop‐signal paradigm

The frontocentral P3 event‐related potential has been proposed as a neural marker of response inhibition. However, this association is disputed: some argue that P3 latency is too late relative to the timing of action stopping (stop‐signal reaction time; SSRT) to index response inhibition. We tested whether P3 onset latency is a marker of response inhibition, and whether it coincides with the timing predicted by neurocomputational models. We measured EEG in 62 participants during the stop‐signal task, and used independent component analysis and permutation statistics to measure the P3 onset in each participant. We show that P3 onset latency is shorter when stopping is successful, that it is highly correlated with SSRT, and that it coincides with the purported timing of the inhibition process (towards the end of SSRT). These results demonstrate the utility of P3 onset latency as a noninvasive, temporally precise neural marker of the response inhibition process.     

Intracortical inhibition during volitional inhibition of prepared action

Volitional inhibition is the voluntary prevention of a prepared movement. Here we ask whether primary motor cortex (M1) is a site of convergence of cortical activity associated with movement preparation and volitional inhibition. Volitional inhibition was studied by presenting a stop signal before execution of an anticipated response that requires a key lift to intercept a revolving dial. Motor evoked potentials (MEPs) were elicited in intrinsic hand muscles by transcranial magnetic stimulation (TMS) to assess corticomotor excitability and short interval intracortical inhibition (sICI) during task performance. The closer the stop cue was presented to the anticipated response, the harder it was for subjects to inhibit their response. Corticomotor pathway excitability was temporally modulated during volitional inhibition. Using subthreshold TMS, corticomotor excitability was reduced for Stop trials relative to Go trials from 140 ms after the cue. sICI was significantly greater for Stop trials compared with Go trials at a time that preceded the onset of muscle activity associated with the anticipated response. These results provide evidence that volitional inhibition is exerted at a cortical level and that inhibitory networks within M1 contribute to volitional inhibition of prepared action.     

Context influences on the preparation and execution of reaching movements

The ability of rapidly adapting our motor behaviour in order to face the unpredictable changes in the surrounding environment is fundamental for survival. To achieve such a high level of efficiency our motor system has to assess continuously the context in which it acts, gathering all available information that can be relevant for planning goal-oriented movements. One still-debated aspect of movement organization is the nature and timing of motor planning. While motor plans are often taken to be concerned with the setting of kinematic parameters as a function of perceptual and motor factors, it has been suggested that higher level, cognitive factors may also affect planning. To explore this issue further, we asked 18 right-handed human participants to perform speeded hand-reaching movement toward a visual target in two different experimental settings, a reaction time (RT) paradigm (go-only task) and a countermanding paradigm. In both tasks participants executed the same movements, but in the countermanding task no-stop trials were randomly intermixed with stop trials. In stop trials participants were required to withhold the ongoing movement whenever a stop signal was shown. It is known that the presence of stop trials induces a consistent increase of the RTs of no-stop trials with respect to the RTs of go-only trials. However, nothing is known about a similar effect for movement times (MTs). We found that RTs and MTs exhibit opposing tendencies, so that a decrease in the RT correspond to an increase in the MT and vice versa. This tendency was present in all our participants and significant in 90% of them. Furthermore we found a moderate, but again very consistent, anticorrelation between RTs and MTs on a trial-by-trial base. These findings are consistent with strategic changes in movement programmes for the very same movements under different cognitive contexts, requiring different degrees of feedback-driven control during movement.     

Measurement of the extraocular spike potential during saccade countermanding

The stop signal task is used to investigate motor inhibition. Several groups have reported partial electromyogram (EMG) activation when subjects successfully withhold manual responses and have used this finding to define the nature of response inhibition properties in the spinal motor system. It is unknown whether subthreshold EMG activation from extraocular muscles can be detected in the saccadic response version of the stop signal task. The saccadic spike potential provides a way to examine extraocular EMG activation associated with eye movements in electroencephalogram (EEG) recordings. We used several techniques to isolate extraocular EMG activation from anterior electrode locations of EEG recorded from macaque monkeys. Robust EMG activation was present when eye movements were made, but no activation was detected when saccades were deemed canceled. This work highlights a key difference between the spinal motor system and the saccade system.     

Context influences on the preparation and execution of reaching movements

The ability of rapidly adapting our motor behaviour in order to face the unpredictable changes in the surrounding environment is fundamental for survival. To achieve such a high level of efficiency our motor system has to assess continuously the context in which it acts, gathering all available information that can be relevant for planning goal-oriented movements. One still-debated aspect of movement organization is the nature and timing of motor planning. While motor plans are often taken to be concerned with the setting of kinematic parameters as a function of perceptual and motor factors, it has been suggested that higher level, cognitive factors may also affect planning. To explore this issue further, we asked 18 right-handed human participants to perform speeded hand-reaching movement toward a visual target in two different experimental settings, a reaction time (RT) paradigm (go-only task) and a countermanding paradigm. In both tasks participants executed the same movements, but in the countermanding task no-stop trials were randomly intermixed with stop trials. In stop trials participants were required to withhold the ongoing movement whenever a stop signal was shown. It is known that the presence of stop trials induces a consistent increase of the RTs of no-stop trials with respect to the RTs of go-only trials. However, nothing is known about a similar effect for movement times (MTs). We found that RTs and MTs exhibit opposing tendencies, so that a decrease in the RT correspond to an increase in the MT and vice versa. This tendency was present in all our participants and significant in 90% of them. Furthermore we found a moderate, but again very consistent, anticorrelation between RTs and MTs on a trial-by-trial base. These findings are consistent with strategic changes in movement programmes for the very same movements under different cognitive contexts, requiring different degrees of feedback-driven control during movement.     

Countermanding eye-head gaze shifts in humans: marching orders are delivered to the head first

The countermanding task requires subjects to cancel a planned movement on appearance of a stop signal, providing insights into response generation and suppression. Here, we studied human eye-head gaze shifts in a countermanding task with targets located beyond the horizontal oculomotor range. Consistent with head-restrained saccadic countermanding studies, the proportion of gaze shifts on stop trials increased the longer the stop signal was delayed after target presentation, and gaze shift stop-signal reaction times (SSRTs: a derived statistic measuring how long it takes to cancel a movement) averaged approximately 120 ms across seven subjects. We also observed a marked proportion of trials (13% of all stop trials) during which gaze remained stable but the head moved toward the target. Such head movements were more common at intermediate stop signal delays. We never observed the converse sequence wherein gaze moved while the head remained stable. SSRTs for head movements averaged approximately 190 ms or approximately 70-75 ms longer than gaze SSRTs. Although our findings are inconsistent with a single race to threshold as proposed for controlling saccadic eye movements, movement parameters on stop trials attested to interactions consistent with a race model architecture. To explain our data, we tested two extensions to the saccadic race model. The first assumed that gaze shifts and head movements are controlled by parallel but independent races. The second model assumed that gaze shifts and head movements are controlled by a single race, preceded by terminal ballistic intervals not under inhibitory control, and that the head-movement branch is activated at a lower threshold. Although simulations of both models produced acceptable fits to the empirical data, we favor the second alternative as it is more parsimonious with recent findings in the oculomotor system. Using the second model, estimates for gaze and head ballistic intervals were approximately 25 and 90 ms, respectively, consistent with the known physiology of the final motor paths. Further, the threshold of the head movement branch was estimated to be 85% of that required to activate gaze shifts. From these results, we conclude that a commitment to a head movement is made in advance of gaze shifts and that the comparative SSRT differences result primarily from biomechanical differences inherent to eye and head motion.     

Individual differences in decisiveness: ERP correlates of response inhibition and error monitoring

The aim of the current study was to examine whether and how self‐reported decisiveness is associated with response inhibition and performance monitoring. We hypothesized that these two cognitive control mechanisms, both of which are often associated with decision making, would differ in individuals varying in decisiveness. We focused on ERP correlates and behavioral measures of inhibition and error processing in the stop‐signal task. We expected a negative relationship between decisiveness and behavioral measures of inhibitory control. We also hypothesized that stop‐signal‐locked N1 and P3 components and response‐locked error‐related negativity (ERN) would be less pronounced when participants self‐reported higher levels of decisiveness. Correlation analysis identified an association between high decisiveness, long stop‐signal reaction time, and low inhibition rate. Analysis with mixed‐effects linear models revealed that stop signals evoked less pronounced N1 and P3 in individuals scoring higher on decisiveness in both successfully and unsuccessfully inhibited trials. Additionally, high decisiveness was linked to reduced error monitoring, as indicated by decreased ERNs. Importantly, we also found positive association between P3 onset latency and decisiveness, suggesting that individuals scoring higher on this measure have relatively less ability to rapidly engage the stopping process. Thus, our findings primarily indicate that decisiveness is negatively associated with the efficiency of both response inhibition and error monitoring. They also suggest that highly decisive people may share some characteristics of diminished cognitive control with impulsive individuals.     

Behavioral evaluation of movement cancellation

The countermanding saccade task has been used in many studies to investigate the neural mechanisms that underlie the decision to execute or restrain rapid eye movements. In this task, the presentation of a saccade target is sometimes followed by the appearance of a stop cue that indicates that the subject should cancel the planned movement. Performance has been modeled as a race between motor preparation and cancellation processes. The signal that reaches its activation threshold first determines whether a saccade is generated or cancelled. In these studies, an important parameter is the time required to process the stop cue, referred to as the stop signal reaction time (SSRT). The SSRT is estimated using statistical approaches, the validity of which has not been unequivocally established. A more direct measure of this parameter might be obtainable if a method was available to "unmask" the developing motor command. This can be accomplished by air-puff-evoked blinks, which inhibit pontine omnipause neurons that serve as an inhibitory gate for the saccadic system. In the present study, brief puffs of air were used to elicit blinks at various times while rhesus monkeys performed a countermanding saccade task. If the developing motor command has not yet been cancelled, this should trigger a saccade. When blinks occurred between approximately 50 and 200 ms after target onset, saccades were often evoked. Saccades were rarely evoked more than approximately 70 ms after stop cue onset; this value represents a behavioral evaluation of SSRT and was comparable to the estimates obtained using standard statistical approaches. When saccades occurred near the SSRT on blink trials, they were often hypometric. Furthermore, Monte Carlo simulations were performed to model the effects of blink time on the race model. Overall, the study supports the validity of the statistical methods currently in use.     

Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson��s disease

Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.     

ERP components associated with successful and unsuccessful stopping in a stop-signal task

The primary aim of this study was to examine how response inhibition is reflected in components of the event-related potential (ERP), using the stop-signal paradigm as a tool to manipulate response inhibition processes. Stop signals elicited a sequence of N2/P3 components that partly overlapped with ERP components elicited by the reaction stimulus. N2/P3 components were more pronounced on stop-signal trials than on no-stop-signal trials. At Cz, the stop-signal P3 peaked earlier on successful than on unsuccessful stop trials. This finding extends the horse race model by demonstrating that the internal response to the stop signal (as reflected in stop-signal P3) is not constant, but terminates at different moments in time on successful and unsuccessful stop trials. In addition, topographical distributions and dipole analysis of high density EEG recordings indicated that different cortical generators were involved in P3s elicited on successful and unsuccessful stop-signal trials. The latter results suggest that P3 on successful stop-signal trials not only reflects stop-signal processing per se, but also efficiency of inhibitory control.     

Fore-period effect and stop-signal reaction time

The effect of response readiness on the stop-signal reaction time (SSRT) in a stop-signal task was examined, with the stop-signal delay updated following a staircase procedure. We computed SSRT on the basis of a horse race model. A fore-period effect was computed, which described subjects’ readiness to respond to the GO signal. The results showed that the fore-period effect correlated positively with SSRT, providing evidence of the effect of response prepotency on stop signal processing. This finding suggests that response readiness needs to be accounted for in examining response inhibition in a stop-signal task.     

ERP correlates of response inhibition after-effects in the stop signal task

Several studies have found that response inhibition in the stop signal task is associated with a delay in subsequent response speed, which may result from the automatic retrieval of a conflicting stimulus-goal association. This study investigated the neurophysiological correlates of this sequence effect using event related potentials (ERPs). ERPs were recorded in 17 healthy people while they performed the stop signal task. We found reduced P3b amplitude for responses following successful inhibition, but only when the stimulus was repeated from the previous trial (repetition-after-effects). For responses following failed inhibition, P3b amplitude was reduced regardless of stimulus repetition status. We also found a general increase in frontal N2 amplitude on response trials following inhibition, regardless of stimulus repetition or behavioural slowing. The complex pattern of ERP findings, dependent on stimulus repetition and success of inhibition, suggests multiple sources of behavioural slowing in the present data. ERP findings suggest that a memory retrieval processes underlies the repetition component of inhibition after effects. These findings are considered within the broader context of ERP findings in the negative priming literature.     

Modulation of short intra-cortical inhibition during action reprogramming

Actions are selected in the context of environmental demands and internal goals. Since both change continuously it is often necessary to inhibit a prepared action plan in favour of an alternative, a process we refer to as action reprogramming. Previous studies have established that a frontal/basal ganglia network exerts top-down control over the primary motor cortex (M1) during action reprogramming. The current study focuses on the role of M1 itself during action reprogramming. Participants were asked to perform a behavioural task that required them to either execute a prepared response or to reprogram an alternative response. Paired-pulse TMS was used to investigate short-interval intra-cortical inhibition (SICI) during these action execution and action reprogramming trials. Normal action execution was associated with sustained SICI in the M1 during both trials in which the contralateral hand was to respond and trials in which the ipsilateral hand was to respond. In contrast, reprogramming towards an alternative action was associated with a progressive release of SICI in M1 involved in the execution of the novel response. This release started 125 ms after the cue telling the participants to reprogram their action. This time point is consistent with previous results showing a facilitatory influence of the pre-supplementary motor area (pre-SMA) on the M1 at the same delay. Hence, SICI might be a potential candidate mechanism through which frontal lobe areas could influence primary motor cortex output.     

Inhibitory control of reaching movements in humans

Behavioral flexibility provides a very large repertoire of actions and strategies, however, it carries a cost: a potential interference between different options. The voluntary control of behavior starts exactly with the ability of deciding between alternatives. Certainly inhibition plays a key role in this process. Here we examined the inhibitory control of reaching arm movements with the countermanding paradigm. Right-handed human subjects were asked to perform speeded reaching movements toward a visual target appearing either on the same or opposite side of the reaching arm (no-stop trials), but to withhold the commanded movement whenever an infrequent stop signal was presented (stop trials). As the delay between go and stop signals increased, subjects increasingly failed to inhibit the movement. From this inhibitory function and the reaction times of movements in no-stop trials, we estimated the otherwise unobservable duration of the stopping process, the stop signal reaction time (SSRT). We found that the SSRT for reaching movements was, on average, 206 ms and that it varied with the reaching arm and the target position even though the stop signal was a central stimulus. In fact, subjects were always faster to withhold reaching movements toward visual targets appearing on the same side of the reaching arm. This behavior strictly parallels the course of the reaction times of no-stop trials. These data show that the stop and go processes interacting in this countermanding task are independent, but most likely influenced by a common factor when under the control of the same hemisphere. In addition, we show that the point beyond which the response cannot be inhibited, the so-called point-of-no-return that divides controlled and ballistic phases of movement processing, lies after the inter-hemispheric transfer.     

How does temporal preparation speed up response implementation in choice tasks? Evidence for an early cortical activation

We investigated the influence of temporal preparation on information processing. Single‐pulse transcranial magnetic stimulation (TMS) of the primary motor cortex was delivered during a between‐hand choice task. The time interval between the warning and the imperative stimulus varied across blocks of trials was either optimal (500 ms) or nonoptimal (2500 ms) for participants' performance. Silent period duration was shorter prior to the first evidence of response selection for the optimal condition. Amplitude of the motor evoked potential specific to the responding hand increased earlier for the optimal condition. These results revealed an early release of cortical inhibition and a faster integration of the response selection‐related inputs to the corticospinal pathway when temporal preparation is better. Temporal preparation may induce cortical activation prior to response selection that speeds up the implementation of the selected response.     

Timing of anticipatory muscle tensing control: responses before and after expected impact

It is widely accepted that human motor control is anticipatory in nature. Previous studies have used electromyography (EMG) to examine muscle responses to falling objects and identified anticipatory muscle tensing (AMT) as a spike in activation that occurs prior to object impact. Some studies have suggested that humans use an internal model of gravity to mediate precisely timed AMT responses. The present study further examines predictive motor control through the analysis of AMT during an object catching task. For some trials, participants watched an object falling toward the hand; for other trials, their eyes were closed. For some trials, the object fell downward and impacted the hand; for other randomly selected trials, the object abruptly stopped 12 cm above the hand, enabling an assessment of the effect of impact anticipation independent of the reflexive tactile response associated with an actual impact. In Experiment 1, AMT did not shift for approximately 113 ms after the abrupt stop of the ball. In Experiment 2, we randomly varied the start height of the object and found well-timed AMT with a 129-ms lag time. A control system based on simple memory for fall time duration cannot explain these findings. We argue that an AMT control system with a lag time of approximately 121 ms could not perform with human levels of accuracy without accounting for the acceleration of downward moving objects.     

The Temporal Dynamics of Response Inhibition and their Modulation by Cognitive Control

Behavioral adjustments require interactions between distinct modes of cognitive control and response inhibition. Hypothetically, fast and global inhibition is exerted in the reactive control mode, whereas proactive control enables the preparation of inhibitory pathways in advance while relying on the slower selective inhibitory system. We compared the temporal progression of inhibition in the reactive and proactive control modes using simultaneous electroencephalography (EEG) and electromyography (EMG) recordings. A selective stop signal task was used where go stimuli required bimanual responses, but only one hand’s response had to be suppressed in stop trials. Reactive and proactive conditions were incorporated by non-informative and informative cues, respectively. In 47% of successful stop trials, subthreshold EMG activity was detected that was interrupted as early as 150 ms after stop stimulus presentation, indicating that inhibition occurs much earlier than previously thought. Inhibition latencies were similar across the reactive and proactive control modes. The EMG of the responding hand in successful selective stop trials indicated a global suppression of ongoing motor actions in the reactive condition, and less inhibitory interference on the ongoing actions in the proactive condition. Group-level second order blind separation (SOBI) was applied to the EEG to dissociate temporally overlapping event-related potentials. The components capturing the N1 and N2 were larger in the reactive than the proactive condition. P3 activity was distributed across four components, three of which were augmented in the proactive condition. Thus, although EEG indices were modulated by the control mode, the inhibition latency remained unaffected.