The human subthalamic nucleus transiently inhibits active attentional processes.

The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson's disease, where modulating the STN via deep brain stimulation (DBS) can release excess inhibition of thalamocortical motor circuits. However, the STN is also anatomically connected to other thalamocortical circuits, including those underlying cognitive processes like attention. Notably, STN-DBS can also affect these processes. This suggests that the STN may also contribute to the inhibition of non-motor activity and that STN-DBS may cause changes to this inhibition. Here we tested this hypothesis in humans. We used a novel, wireless outpatient method to record intracranial local field potentials (LFP) from STN DBS implants during a visual attention task (Experiment 1, n = 12). These outpatient measurements allowed the simultaneous recording of high-density EEG, which we used to derive the steady state visual evoked potential (SSVEP), a well established neural index of visual attentional engagement. By relating STN activity to this neural marker of attention (instead of overt behaviour), we avoided possible confounds resulting from STN's motor role. We aimed to test whether the STN contributes to the momentary inhibition of the SSVEP caused by unexpected, distracting sounds. Furthermore, we causally tested this association in a second experiment, where we modulated STN via DBS across two sessions of the task, spaced at least 1 week apart (n = 21, no sample overlap with Experiment 1). The LFP recordings in Experiment 1 showed that reductions of the SSVEP after distracting sounds were preceded by sound-related γ-frequency (>60 Hz) activity in the STN. Trial-to-trial modelling further showed that this STN activity statistically mediated the sounds' suppressive effect on the SSVEP. In Experiment 2, modulating STN activity via DBS significantly reduced these sound-related SSVEP reductions. This provides causal evidence for the role of the STN in the surprise-related inhibition of attention. These findings suggest that the human STN contributes to the inhibition of attention, a non-motor process. This supports a domain-general view of the inhibitory role of the STN. Furthermore, these findings also suggest a potential mechanism underlying some of the known cognitive side effects of STN-DBS treatment, especially on attentional processes. Finally, our newly established outpatient LFP recording technique facilitates the testing of the role of subcortical nuclei in complex cognitive tasks, alongside recordings from the rest of the brain, and in much shorter time than peri-surgical recordings.

Common and Unique Inhibitory Control Signatures of Action-Stopping and Attentional Capture Suggest That Actions Are Stopped in Two Stages.

The ability to stop an already initiated action is paramount to adaptive behavior. Much scientific debate in the field of human action-stopping currently focuses on two interrelated questions. (1) Which cognitive and neural processes uniquely underpin the implementation of inhibitory control when actions are stopped after explicit stop signals, and which processes are instead commonly evoked by all salient signals, even those that do not require stopping? (2) Why do purported (neuro)physiological signatures of inhibition occur at two different latencies after stop signals? Here, we address both questions via two preregistered experiments that combined measurements of corticospinal excitability, EMG, and whole-scalp EEG. Adult human subjects performed a stop signal task that also contained "ignore" signals: equally salient signals that did not require stopping but rather completion of the Go response. We found that both stop- and ignore signals produced equal amounts of early-latency inhibition of corticospinal excitability and EMG, which took place ∼150 ms following either signal. Multivariate pattern analysis of the whole-scalp EEG data further corroborated that this early processing stage was shared between stop- and ignore signals, as neural activity following the two signals could not be decoded from each other until a later time period. In this later period, unique activity related to stop signals emerged at frontocentral scalp sites, reflecting an increased stop signal P3. These findings suggest a two-step model of action-stopping, according to which an initial, universal inhibitory response to the saliency of the stop signal is followed by a slower process that is unique to outright stopping.SIGNIFICANCE STATEMENT Humans often have to stop their ongoing actions when indicated by environmental stimuli (stop signals). Successful action-stopping requires both the ability to detect these salient stop signals and to subsequently inhibit ongoing motor programs. Because of this tight entanglement of attentional control and motor inhibition, identifying unique neurophysiological signatures of action-stopping is difficult. Indeed, we report that recently proposed early-latency signatures of motor inhibition during action-stopping are also found after salient signals that do not require stopping. However, using multivariate pattern analysis of scalp-recorded neural data, we also identified subsequent neural activity that uniquely distinguished action-stopping from saliency detection. These results suggest that actions are stopped in two stages: the first common to all salient events and the second unique to action-stopping.

Unexpected Sounds Nonselectively Inhibit Active Visual Stimulus Representations.

The brain's capacity to process unexpected events is key to cognitive flexibility. The most well-known effect of unexpected events is the interruption of attentional engagement (distraction). We tested whether unexpected events interrupt attentional representations by activating a neural mechanism for inhibitory control. This mechanism is most well characterized within the motor system. However, recent work showed that it is automatically activated by unexpected events and can explain some of their nonmotor effects (e.g., on working memory representations). Here, human participants attended to lateralized flickering visual stimuli, producing steady-state visual evoked potentials (SSVEPs) in the scalp electroencephalogram. After unexpected sounds, the SSVEP was rapidly suppressed. Using a functional localizer (stop-signal) task and independent component analysis, we then identified a fronto-central EEG source whose activity indexes inhibitory motor control. Unexpected sounds in the SSVEP task also activated this source. Using single-trial analyses, we found that subcomponents of this source differentially relate to sound-induced SSVEP changes: While its N2 component predicted the subsequent suppression of the attended-stimulus SSVEP, the P3 component predicted the suppression of the SSVEP to the unattended stimulus. These results shed new light on the processes underlying fronto-central control signals and have implications for phenomena such as distraction and the attentional blink.

Adjustments to Proactive Motor Inhibition without Effector-Specific Foreknowledge Are Reflected in a Bilateral Upregulation of Sensorimotor ß-Burst Rates.

Classic work using the stop-signal task has shown that humans can use inhibitory control to cancel already initiated movements. Subsequent work revealed that inhibitory control can be proactively recruited in anticipation of a potential stop-signal, thereby increasing the likelihood of successful movement cancellation. However, the exact neurophysiological effects of proactive inhibitory control on the motor system are still unclear. On the basis of classic views of sensorimotor ß-band activity, as well as recent findings demonstrating the burst-like nature of this signal, we recently proposed that proactive inhibitory control is implemented by influencing the rate of sensorimotor ß-bursts during movement initiation. Here, we directly tested this hypothesis using scalp EEG recordings of ß-band activity in 41 healthy human adults during a bimanual RT task. By comparing motor responses made in two different contexts-during blocks with or without stop-signals-we found that premovement ß-burst rates over both contralateral and ipsilateral sensorimotor areas were increased in stop-signal blocks compared to pure-go blocks. Moreover, the degree of this burst rate difference indexed the behavioral implementation of proactive inhibition (i.e., the degree of anticipatory response slowing in the stop-signal blocks). Finally, exploratory analyses showed that these condition differences were explained by a significant increase in ß bursting that was already present during baseline period before the movement initiation signal. Together, this suggests that the strategic deployment of proactive inhibitory motor control is implemented by upregulating the tonic inhibition of the motor system, signified by increased sensorimotor ß-bursting both before and after signals to initiate a movement.

Paired-pulse TMS and scalp EEG reveal systematic relationship between inhibitory GABAa signaling in M1 and fronto-central cortical activity during action stopping.

By stopping actions even after their initiation, humans can flexibly adapt ongoing behavior to changing circumstances. The neural processes underlying the inhibition of movement during action stopping are still controversial. In the 90s, a fronto-central event-related potential (ERP) was discovered in the human EEG response to stop signals in the classic stop-signal task, alongside a proposal that this "stop-signal P3" reflects an inhibitory process. Indeed, both amplitude and onset of the stop-signal P3 relate to overt behavior and movement-related EEG activity in ways predicted by the dominant models of action-stopping. However, neither EEG nor behavior allow direct inferences about the presence or absence of neurophysiological inhibition of the motor cortex, making it impossible to definitively relate the stop-signal P3 to inhibition. Here, we therefore present a multimethod investigation of the relationship between the stop-signal P3 and GABAergic signaling in primary motor cortex, as indexed by paired-pulse transcranial magnetic stimulation (TMS). In detail, we measured short-interval intracortical inhibition (SICI), a marker of inhibitory GABAa activity in M1, in a group of 41 human participants who also performed the stop-signal task while undergoing EEG recordings. In line with the P3-inhibition hypothesis, we found that subjects with stronger inhibitory GABA activity in M1 also showed both faster onsets and larger amplitudes of the stop-signal P3. This provides direct evidence linking the properties of this ERP to a true physiological index of motor system inhibition. We discuss these findings in the context of recent theoretical developments and empirical findings regarding the neural implementation of motor inhibition.NEW & NOTEWORTHY The neural mechanisms underlying rapid action stopping in humans are subject to intense debate, in part because recordings of neural signals purportedly reflecting inhibitory motor control are hard to directly relate to the true, physiological inhibition of motor cortex. For the first time, the current study combines EEG and transcranial magnetic stimulation (TMS) methods to demonstrate a direct correspondence between fronto-central control-related EEG activity following signals to cancel an action and the physiological inhibition of primary motor cortex.