Double-blind disruption of right inferior frontal cortex with TMS reduces right frontal beta power for action stopping.

Stopping action depends on the integrity of the right inferior frontal gyrus (rIFG). Electrocorticography from the rIFG shows an increase in beta power during action stopping. Scalp EEG shows a similar right frontal beta increase, but it is unknown whether this beta modulation relates to the underlying rIFG network. Demonstrating a causal relationship between the rIFG and right frontal beta in EEG during action stopping is important for putting this electrophysiological marker on a firmer footing. In a double-blind study with a true sham coil, we used fMRI-guided 1-Hz repetitive transcranial magnetic stimulation (rTMS) to disrupt the rIFG and to test whether this reduced right frontal beta and impaired action stopping. We found that rTMS selectively slowed stop signal reaction time (SSRT) (no effect on Go) and reduced right frontal beta (no effect on sensorimotor mu/beta related to Go); it also reduced the variance of a single-trial muscle marker of stopping. Surprisingly, sham stimulation also slowed SSRTs and reduced beta. Part of this effect, however, resulted from carryover of real stimulation in participants who received real stimulation first. A post hoc between-group comparison of those participants who received real first compared with those who received sham first showed that real stimulation reduced beta significantly more. Thus, real rTMS uniquely affected metrics of stopping in the muscle and resulted in a stronger erosion of beta. We argue that this causal test validates right frontal beta as a functional marker of action stopping.NEW & NOTEWORTHY Action stopping recruits the right inferior frontal gyrus (rIFG) and elicits increases in right frontal beta. The present study now provides causal evidence linking these stopping-related beta oscillations to the integrity of the underlying rIFG network. One-hertz transcranial magnetic stimulation (TMS) over the rIFG impaired stopping and reduced right frontal beta during a stop-signal task. Furthermore, the effect on neural oscillations was specific to stopping-related beta, with no change in sensorimotor mu/beta corresponding to the Go response.

Temporally-precise disruption of prefrontal cortex informed by the timing of beta bursts impairs human action-stopping.

Human action-stopping is thought to rely on a prefronto-basal ganglia-thalamocortical network, with right inferior frontal cortex (rIFC) posited to play a critical role in the early stage of implementation. Here we sought causal evidence for this idea in experiments involving healthy human participants. We first show that action-stopping is preceded by bursts of electroencephalographic activity in the beta band over prefrontal electrodes, putatively rIFC, and that the timing of these bursts correlates with the latency of stopping at a single-trial level: earlier bursts are associated with faster stopping. From this we reasoned that the integrity of rIFC at the time of beta bursts might be critical to successful stopping. We then used fMRI-guided transcranial magnetic stimulation (TMS) to disrupt rIFC at the approximate time of beta bursting. Stimulation prolonged stopping latencies and, moreover, the prolongation was most pronounced in individuals for whom the pulse appeared closer to the presumed time of beta bursting. These results help validate a model of the neural architecture and temporal dynamics of action-stopping. They also highlight the usefulness of prefrontal beta bursts to index an apparently important sub-process of stopping, the timing of which might help explain within- and between-individual variation in impulse control.

The Functional Role of Response Suppression during an Urge to Relieve Pain.

Being in the state of having both a strong impulse to act and a simultaneous need to withhold is commonly described as an "urge." Although urges are part of everyday life and also important to several clinical disorders, the components of urge are poorly understood. It has been conjectured that withholding an action during urge involves active response suppression. We tested that idea by designing an urge paradigm that required participants to resist an impulse to press a button and gain relief from heat (one hand was poised to press while the other arm had heat stimulation). We first used paired-pulse TMS over motor cortex (M1) to measure corticospinal excitability of the hand that could press for relief, while participants withheld movement. We observed increased short-interval intracortical inhibition, an index of M1 GABAergic interneuron activity that was maintained across seconds and specific to the task-relevant finger. A second experiment replicated this. We next used EEG to better "image" putative cortical signatures of motor suppression and pain. We found increased sensorimotor beta contralateral to the task-relevant hand while participants withheld the movement during heat. We interpret this as further evidence of a motor suppressive process. Additionally, there was beta desynchronization contralateral to the arm with heat, which could reflect a pain signature. Strikingly, participants who "suppressed" more exhibited less of a putative "pain" response. We speculate that, during urge, a suppressive state may have functional relevance for both resisting a prohibited action and for mitigating discomfort.

Visual attraction in Drosophila larvae develops during a critical period and is modulated by crowding conditions.

The development of social behavior is poorly understood. Many animals adjust their behavior to environmental conditions based on a social context. Despite having relatively simple visual systems, Drosophila larvae are capable of identifying and are attracted to the movements of other larvae. Here, we show that Drosophila larval visual recognition is encoded by the movements of nearby larvae, experienced during a specific developmental critical period. Exposure to moving larvae, only during a specific period, is sufficient for later visual recognition of movement. Larvae exposed to wild-type body movements, during the critical period, are not attracted to the movements of tubby mutants, which have altered morphology. However, exposure to tubby, during the critical period, results in tubby recognition at the expense of wild-type recognition indicating that this is true learning. Visual recognition is not learned in excessively crowded conditions, and this is emulated by exposure, during the critical period, to food previously used by crowded larvae. We propose that Drosophila larvae have a distinct critical period, during which they assess both social and resource conditions, and that this irreversibly determines later visually guided social behavior. This model provides a platform towards understanding the regulation and development of social behavior.

Neural Correlates of Compulsive Alcohol Seeking in Heavy Drinkers.

BACKGROUND: Compulsive alcohol use, the tendency to continue alcohol seeking and taking despite negative consequences, is a hallmark of alcohol use disorder. Preclinical rodent studies have suggested a role for the medial prefrontal cortex, anterior insula, and nucleus accumbens in compulsive alcohol seeking. It is presently unknown whether these findings translate to humans. We used a novel functional magnetic resonance imaging paradigm and tested the hypothesis that heavy drinkers would compulsively seek alcohol despite the risk of an aversive consequence, and that this behavior would be associated with the activity of frontostriatal circuitry. METHODS: Non-treatment-seeking heavy and light drinkers (n = 21 per group) completed a functional magnetic resonance imaging paradigm in which they could earn alcohol or food points at various threat levels (i.e., various probabilities of incurring an aversive consequence). Brain function was evaluated when individuals had the opportunity to earn reward points at the risk of an aversive consequence, an electric shock on the wrist. RESULTS: Compared with light drinkers, heavy drinkers attempted to earn more aversion-paired alcohol points. Frontostriatal circuitry, including the medial prefrontal cortex, anterior insula, and striatum, was more active in this group when viewing threat-predictive alcohol cues. Heavy drinkers had increased connectivity between the anterior insula and the nucleus accumbens. Greater connectivity was associated with more attempts to earn aversion-paired alcohol points and self-reported compulsive alcohol use scores. CONCLUSIONS: Higher activation of frontostriatal circuitry in heavy drinkers may contribute to compulsive alcohol seeking. Treatments that disrupt this circuitry may result in a decrease in compulsive alcohol use.

Alcohol Dependence and Altered Engagement of Brain Networks in Risky Decisions.

Alcohol dependence is associated with heightened risk tolerance and altered decision-making. This raises the question as to whether alcohol dependent patients (ADP) are incapable of proper risk assessment. We investigated how healthy controls (HC) and ADP engage neural networks to cope with the increased cognitive demands of risky decisions. We collected fMRI data while 34 HC and 16 ADP played a game that included "safe" and "risky" trials. In safe trials, participants accrued money at no risk of a penalty. In risky trials, reward and risk simultaneously increased as participants were instructed to decide when to stop a reward accrual period. If the participant failed to stop before an undisclosed time, the trial would "bust" and participants would not earn the money from that trial. Independent Component Analysis was used to identify networks engaged during the anticipation and the decision execution of risky compared with safe trials. Like HC, ADP demonstrated distinct network engagement for safe and risky trials at anticipation. However, at decision execution, ADP exhibited severely reduced discrimination in network engagement between safe and risky trials. Although ADP behaviorally responded to risk they failed to appropriately modify network engagement as the decision continued, leading ADP to assume similar network engagement regardless of risk prospects. This may reflect disorganized network switching and a facile response strategy uniformly adopted by ADP across risk conditions. We propose that aberrant salience network (SN) engagement in ADP might contribute to ineffective network switching and that the role of the SN in risky decisions warrants further investigation.