Brain modular connectivity interactions can predict proactive inhibition in smokers when facing smoking cues.

Proactive inhibition is a critical ability for smokers who seek to moderate or quit smoking. It allows them to pre-emptively refrain from seeking and using nicotine products, especially when facing salient smoking cues in daily life. Nevertheless, there is limited knowledge on the impact of salient cues on behavioural and neural aspects of proactive inhibition, especially in smokers with nicotine withdrawal. Here, we seek to bridge this gap. To this end, we recruited 26 smokers to complete a stop-signal anticipant task (SSAT) in two separate sessions: once in the neutral cue condition and once in the smoking cue condition. We used graph-based modularity analysis to identify the modular structures of proactive inhibition-related network during the SSAT and further investigated how the interactions within and between these modules could be modulated by different proactive inhibition demands and salient smoking cues. Findings pointed to three stable brain modules involved in the dynamical processes of proactive inhibition: the sensorimotor network (SMN), cognitive control network (CCN) and default-mode network (DMN). With the increase in demands, functional connectivity increased within the SMN, CCN and between SMN-CCN and decreased within the DMN and between SMN-DMN and CCN-DMN. Salient smoking cues disturbed the effective dynamic interactions of brain modules. The profiles for those functional interactions successfully predicted the behavioural performance of proactive inhibition in abstinent smokers. These findings advance our understanding of the neural mechanisms of proactive inhibition from a large-scale network perspective. They can shed light on developing specific interventions for abstinent smokers.

Proactive inhibition is marked by differences in the pattern of motor cortex activity during movement preparation and execution.

Successful human behavior relies on the ability to flexibly alter movements depending on the context in which they are made. One such context-dependent modulation is proactive inhibition, a type of behavioral inhibition used when anticipating the need to stop or change movements. We investigated how the motor cortex might prepare and execute movements made under different contexts. We used transcranial magnetic stimulation (TMS) in different coil orientations [postero-anterior (PA) and antero-posterior (AP) flowing currents] and pulse widths (120 and 30 µs) to probe the excitability of different inputs to corticospinal neurons while participants performed two reaction time tasks: a simple reaction time task and a stop-signal task requiring proactive inhibition. We took inspiration from state space models to assess whether the pattern of motor cortex activity changed due to proactive inhibition (PA and AP neuronal circuits represent the x and y axes of a state space upon which motor cortex activity unfolds during motor preparation and execution). We found that the rise in motor cortex excitability was delayed when proactive inhibition was required. State space visualizations showed altered patterns of motor cortex activity (combined PA120 and AP30 activity) during proactive inhibition, despite adjusting for reaction time. Overall, we show that the pattern of neural activity generated by the motor cortex during movement preparation and execution is dependent upon the context under which the movement is to be made.NEW & NOTEWORTHY Using directional TMS, we find that the human motor cortex flexibly changes its pattern of neural activity depending on the context in which a movement is due to be made. Interestingly, this occurs despite adjusting for reaction time. We also show that state space and dynamical systems models of movement can be noninvasively visualized in humans using TMS, thereby offering a novel method to study these powerful models in humans.

Memory and Proactive Interference for spatially distributed items.

Our ability to briefly retain information is often limited. Proactive Interference (PI) might contribute to these limitations (e.g., when items in recognition tests are difficult to reject after having appeared recently). In visual Working Memory (WM), spatial information might protect WM against PI, especially if encoding items together with their spatial locations makes item-location combinations less confusable than simple items without a spatial component. Here, I ask (1) if PI is observed for spatially distributed items, (2) if it arises among simple items or among item-location combinations, and (3) if spatial information affects PI at all. I show that, contrary to views that spatial information protects against PI, PI is reliably observed for spatially distributed items except when it is weak. PI mostly reflects items that appear recently or frequently as memory items, while occurrences as test items play a smaller role, presumably because their temporal context is easier to encode. Through mathematical modeling, I then show that interference occurs among simple items rather than item-location combinations. Finally, to understand the effects of spatial information, I separate the effects of (a) the presence and (b) the predictiveness of spatial information on memory and its susceptibility to PI. Memory is impaired when items are spatially distributed, but, depending on the analysis, unaffected by the predictiveness of spatial information. In contrast, the susceptibility to PI is unaffected by either manipulation. Visual memory is thus impaired by PI for spatially distributed items due to interference from recent memory items (rather than test items or item-location combinations).

Does testing enhance new learning because it insulates against proactive interference?

Taking a test on previously learned material can enhance new learning. One explanation for this forward testing effect is that retrieval inoculates learners from proactive interference (PI). Although this release-from-PI account has received considerable empirical support, most extant evidence is correlational rather than causal. We tested this account by manipulating the level of PI that participants experience as they studied several lists while receiving interpolated tests or not. In Experiments 1 and 2, we found that testing benefited new learning similarly regardless of PI level. These results contradict those from Nunes and Weinstein (Memory, 20(2), 138-154, 2012), who found no forward testing effect when encoding conditions minimized PI. In Experiments 3 and 4, we failed to replicate their results. Together, our data indicate that reduced PI might be a byproduct, rather than a causal factor, of the forward testing effect.

Magnitude and sources of proactive interference in visual memory.

Proactive interference - the disruptive effect of old memories on new learning - is a long-established forgetting mechanism, yet there are doubts about its impact on visual working memory and uncertainty about the kinds of information that cause proactive interference. The present study aimed to assess these issues in three experiments using a modified recent probes task. Participants encoded four target images on each trial and determined whether a probe matched one of those targets. In Experiment 1, probes matching targets from trial N-1 or N-3 damaged responding in relation to a novel probe. Proactive interference was also produced by probes differing in state to a previously experienced target. This was further assessed in Experiments 2 and 3. Here, probes differing in colour to a previous target, or matching the general target category only, produced little proactive interference. Conversely, probes directly matching a prior target, or differing in state information, hindered task performance. This study found robust proactive interference in visual working memory that could endure over multiple trials, but it was also produced by stimuli closely resembling an old target. This challenges the notion that proactive interference is produced by an exact representation of a previously encoded image.

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.

Intact Proactive Motor Inhibition after Unilateral Prefrontal Cortex or Basal Ganglia Lesions.

Previous research provided evidence for the critical importance of the PFC and BG for reactive motor inhibition, that is, when actions are cancelled in response to external signals. Less is known about the role of the PFC and BG in proactive motor inhibition, referring to preparation for an upcoming stop signal. In this study, patients with unilateral lesions to the BG or lateral PFC performed in a cued go/no-go task, whereas their EEG was recorded. The paradigm called for cue-based preparation for upcoming, lateralized no-go signals. Based on previous findings, we focused on EEG indices of cognitive control (prefrontal beta), motor preparation (sensorimotor mu/beta, contingent negative variation [CNV]), and preparatory attention (occipital alpha, CNV). On a behavioral level, no differences between patients and controls were found, suggesting an intact ability to proactively prepare for motor inhibition. Patients showed an altered preparatory CNV effect, but no other differences in electrophysiological activity related to proactive and reactive motor inhibition. Our results suggest a context-dependent role of BG and PFC structures in motor inhibition, being critical in reactive, unpredictable contexts, but less so in situations where one can prepare for stopping on a short timescale.

Proactive inhibition is not modified by deep brain stimulation for Parkinson's disease: An electrical neuroimaging study.

In predictable contexts, motor inhibitory control can be deployed before the actual need for response suppression. The brain functional underpinnings of proactive inhibition, and notably the role of basal ganglia, are not entirely identified. We investigated the effects of deep brain stimulation of the subthalamic nucleus or internal globus pallidus on proactive inhibition in patients with Parkinson's disease. They completed a cued go/no-go proactive inhibition task ON and (unilateral) OFF stimulation while EEG was recorded. We found no behavioural effect of either subthalamic nucleus or internal globus pallidus deep brain stimulation on proactive inhibition, despite a general improvement of motor performance with subthalamic nucleus stimulation. In the non-operated and subthalamic nucleus group, we identified periods of topographic EEG modulation by the level of proactive inhibition. In the subthalamic nucleus group, source estimation analysis suggested the initial involvement of bilateral frontal and occipital areas, followed by a right lateralized fronto-basal network, and finally of right premotor and left parietal regions. Our results confirm the overall preservation of proactive inhibition capacities in both subthalamic nucleus and internal globus pallidus deep brain stimulation, and suggest a partly segregated network for proactive inhibition, with a preferential recruitment of the indirect pathway.

Two sides of the same coin: ADHD affects reactive but not proactive inhibition in children.

Children with attention-deficit/hyperactivity disorder (ADHD) present a deficit in inhibitory control. Still, it remains unclear whether it comes from a deficit in reactive inhibition (ability to stop the action in progress), proactive inhibition (ability to exert preparatory control), or both.We compared the performance of 39 children with ADHD and 42 typically developing children performing a Simon choice reaction time task. The Simon task is a conflict task that is well-adapted to dissociate proactive and reactive inhibition. Beyond classical global measures (mean reaction time, accuracy rate, and interference effect), we used more sophisticated dynamic analyses of the interference effect and accuracy rate to investigate reactive inhibition. We studied proactive inhibition through the congruency sequence effect (CSE).Our results showed that children with ADHD had impaired reactive but not proactive inhibition. Moreover, the deficit found in reactive inhibition seems to be due to both a stronger impulse capture and more difficulties in inhibiting impulsive responses. These findings contribute to a better understanding of how ADHD affects inhibitory control in children.

Effects of motor restrictions on preparatory brain activity.

Modifying established motor skills is a challenging endeavor due to proactive interference from undesired old to desired new actions, calling for high levels of cognitive control. Motor restrictions may facilitate the modification of motor skills by rendering undesired responses physically impossible, thus reducing demands to response inhibition. Here we studied behavioral and EEG effects of rule changes to typing in skilled touch-typists. The respective rule change-typing without using the left index finger-was either implemented per instruction only or with an additional motor restriction. In both groups, the rule change elicited delays and more errors in typing, indicating the occurrence of proactive interference. While stimulus-locked ERPs did not exhibit prominent effects of rule change or group, response-locked ERPs revealed that the time courses of preparatory brain activity preceding typing responses depended on the presence of motor restriction. Although further research is necessary to corroborate our findings, they indicate a novel brain correlate that represents changes in inhibitory response preparation induced by short-term motor restrictions.

How Proactive Interference during New Associative Learning Impacts General and Specific Memory in Young and Old.

Some prior research has found that older adults are more susceptible to proactive interference than young adults. The current study investigated whether age-related deficits in pFC-mediated cognitive control processes that act to detect and resolve interference underlie increased susceptibility to proactive interference in an associative memory task. Young and older adults were scanned while tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high, low, or no proactive interference. After scanning, participants' memory was tested for varying levels of episodic detail about the pairings (i.e., target category vs. specific target category vs. specific target associate). Young and older adults were similarly susceptible to proactive interference. Memory for both the general target category and the specific target associate worsened as the level of proactive interference increased, with no robust age differences. For both young and older adults, the left ventrolateral pFC, which has been indicated in controlled retrieval of goal-relevant conceptual representations, was sensitive to increasing levels of interference during encoding but was insensitive to associative memory accuracy. Consistent with the Compensation-Related Utilization of Neural Circuits Hypothesis model of cognitive aging, the ventromedial pFC, which is involved in the monitoring of internally generated information, was recruited more by older than young adults to support the successful retrieval of target-object pairs at lower levels of proactive interference. Collectively, these results suggest that some older adults are able to engage in the cognitive control processes necessary to resolve proactive interference to the same extent as young adults.

Early-stage Parkinson's patients show selective impairment in reactive but not proactive inhibition.

BACKGROUND: It is well known that a deficit in inhibitory control is a hallmark of Parkinson's disease (PD). However, inhibition is not a unitary construct, and it is unclear whether patients in the early stage of the disease (Hoehn and Yahr stage 1) exhibit a deficit in outright stopping (reactive inhibition), a deficit in the ability to shape their response strategies according to the context (proactive inhibition), or both. OBJECTIVE: We assessed whether PD patients at Hoehn and Yahr stage 1 show a global or selective impairment in inhibitory control. As it has been suggested that inhibition relies upon a right-lateralized pathway, we tested whether left-dominant PD patients suffered from a more severe deficit in this executive function than right-dominant PD patients. METHODS: Via a reaching stop-signal task, we assessed both proactive and reactive inhibition in 17 left-dominant PD and 17 right-dominant PD patients and in 24 age-matched participants. RESULTS: We found that reactive inhibition was more impaired in PD patients than in healthy participants. However, proactive inhibition was not affected. Furthermore, we found no differences between left-dominant PD and right-dominant PD patients. CONCLUSIONS: For the first time, we found evidence for a deficit of reactive inhibition in the early-stage PD patients in the absence of evidence for deficits in proactive inhibition. These findings have clinical relevance as they provide critical insights on the time course of the disease. In addition, we confirmed, on a population of PD patients at Hoehn and Yahr stage 1, previous results showing that the onset of the disease does not affect inhibition. © 2019 International Parkinson and Movement Disorder Society.

The role of attentional fluctuation during study in recollecting episodic changes at test.

Changes in stimulus features across episodes can lead to proactive interference. One potential way to avoid such interference is to detect and later recollect changes. The Memory-for-Change framework assumes that attention during encoding is necessary for detecting and later recollecting change. We tested this assumption in the current experiment by assessing the covariation of attention and change recollection in a large undergraduate sample (N=132). Participants studied a list of word pairs comprised of four seamless blocks. Some word pairs repeated across all four blocks (A-B4), some were unique to each block (C-D), and some pairs repeated across the first three blocks with a changed response in the fourth block (A-B3, A-D). To measure attention during study, participants periodically responded to probes asking whether they were on- or off-task. Participants then completed a cued recall test of responses from the fourth study block. To measure change recollection, participants were asked to identify which pairs changed during study and to report the earlier responses for pairs they identified as changed. Replicating prior findings, recollecting change was associated with proactive facilitation in recall of the most recent responses. Extending these findings, the frequency of on-task reports was positively associated with cued recall accuracy and change recollection in both within- and between-subjects comparisons. Together, these findings implicate a critical role for self-reported attention during study in change recollection, which is associated with proactive facilitation in recall of changed responses.

Too much of a good thing: frequent retrieval can impair immediate new learning.

Interpolated testing can reduce mind-wandering and proactive interference, and improve note-taking. However, recent research using face-name-profession triads, has also shown that interpolated testing can impair new learning (Davis, Chan, & Wilford, 2017). In the current study, we further examined the impact of switching from testing to new learning, but with objectively-true materials. The study employed a 2 (Interpolated task: Test vs. Restudy) × 3 (Task-switch frequency: 0, 11, 35) between-participants design. In two experiments, participants restudied or retrieved originally-learned flag-country associations and learned new flag-capital (Experiment 1) or flag-export (Experiment 2) associations. Task-switch frequency varied such that participants switched to new learning trial(s) after every restudy/test trial (35-switches), after every three restudy/test trials (11-switches), or did not switch at all (0-switch). The results further demonstrate that retrieving previously-learned material can impair learning of new associations by replicating Davis et al. (2017) with objectively-true materials.

Impulsivity trait and proactive cognitive control: An fMRI study.

The ability to flexibly regulate our behavior is a fundamental feature of human cognition and requires efficient functioning of cognitive control. During movement preparation, proactive inhibitory control plays a crucial role in regulating the excitatory activity carried out by alertness. The balance between alertness and proactive inhibition could be altered in people with motor impulsivity trait, determining the typical failure in the inhibition of prepotent motor responses. To test this hypothesis, 36 young adults were administered the Barratt Impulsiveness Scale to assess motor impulsivity trait and underwent fMRI acquisition during the execution of an event-related Go/Nogo task. To investigate motor preparation processes, we analyzed the "readiness" period, in which subjects were waiting and preparing for the upcoming stimulus (Go or Nogo). We found a positive significant correlation between motor impulsivity scores and the activation of left sensorimotor cortices. This result indicates that motor impulsivity trait might be associated with a disinhibition of the motor system, characterized by a diminished reactivity threshold and a reduced control over covert urges. Furthermore, we observed a positive significant correlation between motor impulsivity scores and the activation in left inferior and superior parietal lobule, which might be related to a more pronounced proactive control, probably reflecting a compensatory mechanism implemented by participants with a higher degree of motor impulsivity trait to reach a correct inhibition. Current findings provide a rationale for further studies aiming to better understand proactive control functioning in healthy impulsive subjects and under clinical conditions.

Using subjective expectations to model the neural underpinnings of proactive inhibition.

Proactive inhibition - the anticipation of having to stop a response - relies on objective information contained in cue-related contingencies in the environment, as well as on the subjective interpretation derived from these cues. To date, most studies of brain areas underlying proactive inhibition have exclusively considered the objective predictive value of environmental cues, by varying the probability of stop-signals. However, by only taking into account the effect of different cues on brain activation, the subjective component of how cues affect behavior is ignored. We used a modified stop-signal response task that includes a measurement for subjective expectation, to investigate the effect of this subjective interpretation. After presenting a cue indicating the probability that a stop-signal will occur, subjects were asked whether they expected a stop-signal to occur. Furthermore, response time was used to retrospectively model brain activation related to stop-expectation. We found more activation during the cue period for 50% stop-signal probability, when contrasting with 0%, in the mid and inferior frontal gyrus, inferior parietal lobe and putamen. When contrasting expected vs. unexpected trials, we found modest effects in the mid frontal gyrus, parietal, and occipital areas. With our third contrast, we modeled brain activation during the cue with trial-by-trial variances in response times. This yielded activation in the putamen, inferior parietal lobe, and mid frontal gyrus. Our study is the first to use the behavioral effects of proactive inhibition to identify the underlying brain regions, by employing an unbiased task-design that temporally separates cue and response.

Proactive inhibition deficits with normal perfusion after pediatric mild traumatic brain injury.

Although much attention has been generated in popular media regarding the deleterious effects of pediatric mild traumatic brain injury (pmTBI), a paucity of empirical evidence exists regarding the natural course of biological recovery. Fifty pmTBI patients (12-18 years old) were consecutively recruited from Emergency Departments and seen approximately 1 week and 4 months post-injury in this prospective cohort study. Data from 53 sex- and age-matched healthy controls (HC) were also collected. Functional magnetic resonance imaging was obtained during proactive response inhibition and at rest, in conjunction with independent measures of resting cerebral blood flow. High temporal resolution imaging enabled separate modeling of neural responses for preparation and execution of proactive response inhibition. A priori predictions of failed inhibitory responses (i.e., hyperactivation) were observed in motor circuitry (pmTBI>HC) and sensory areas sub-acutely and at 4 months post-injury. Paradoxically, pmTBI demonstrated hypoactivation (HC>pmTBI) during target processing, along with decreased activation within prefrontal cognitive control areas. Functional connectivity within motor circuitry at rest suggested that deficits were limited to engagement during the inhibitory task, whereas normal resting cerebral perfusion ruled out deficits in basal perfusion. In conclusion, current results suggest blood oxygen-level dependent deficits during inhibitory control may exceed commonly held beliefs about physiological recovery following pmTBI, potentially lasting up to 4 months post-injury.

Children with ADHD symptoms show deficits in reactive but not proactive inhibition, irrespective of their formal diagnosis.

BACKGROUND: Attenuated inhibitory control is one of the most robust findings in the neuropsychology of attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether this represents a deficit in outright stopping (reactive inhibition), whether it relates to a deficit in anticipatory response slowing (proactive inhibition), or both. In addition, children with other development disorders, such as autism spectrum disorder (ASD), often have symptoms of inattention, impulsivity, and hyperactivity similar to children with ADHD. These may relate to similar underlying changes in inhibitory processing. METHODS: In this study, we used a modified stop-signal task to dissociate reactive and proactive inhibition. We included not only children with ADHD, but also children primarily diagnosed with an ASD and high parent-rated levels of ADHD symptoms. RESULTS: We replicated the well-documented finding of attenuated reactive inhibition in children with ADHD. In addition, we found a similar deficit in children with ASD and a similar level of ADHD symptoms. In contrast, we found no evidence for deficits in proactive inhibition in either clinical group. CONCLUSIONS: These findings re-emphasize the role of reactive inhibition in children with ADHD and ADHD symptoms. Moreover, our findings stress the importance of a trans-diagnostic approach to the relationship between behavior and neuropsychology.

Evaluating Proactive Strategy in Patients With OCD During Stop Signal Task.

OBJECTIVES: The aim of the present study was to investigate "Proactive-Adjustment hypothesis" (PA) during the Stop Signal Task (SST). The PA is implied in the highly inconsistent literature, and it deals with the role of response inhibition (RI) in obsessive-compulsive disorder (OCD). This hypothesis assumed that participants would balance stopping and going by adjusting the response threshold (RT) in the go task. We verified whether the PA strategy was also implemented in our clinical group. METHODS: To reach this goal, we analyzed SST performances in a group of 36 patients with OCD and 36 healthy controls (HCs). To identify different participants' behaviors during the task, without preconceived notions regarding the diagnosis, we performed a cluster analysis. Furthermore, we analyzed the influence of drug therapy and we investigated whether the rule and reversal acquisition investigated with the Intra-Extra Dimensional Set Shift, differed in the two clusters. RESULTS: We did not find any difference relative to the number of patients with OCD and HCs included in the two clusters. Furthermore, we found that only Not Proactive participants performed the task as fast as possible, while Proactive participants consistently slowed down their RTs and showed a lower number of Direction Errors, higher Stop Signal Delay, and worse cognitive flexibility. CONCLUSIONS: Our results show that among patients with OCD the use of PA is changeable and does not differ from HCs. This finding supports the idea that the RI heterogeneity concerning patients with OCD could be related to PA. (JINS, 2018, 24, 703-714).

Blocked vs. interleaved presentation and proactive interference in episodic memory.

Although a number of theoretical accounts of proactive interference (PI) in episodic memory have been proposed, existing empirical evidence does not support conclusively a single view yet. In two experiments we tested the predictions of the temporal discrimination theory of PI against alternative accounts by manipulating the presentation schedule of study materials (lists blocked by category vs. interleaved). In line with the temporal discrimination theory, we observed a clear buildup of (and release from) PI in the blocked condition, in which all the lists of the same category were presented sequentially. In the interleaved condition, with alternating lists of different categories, a more gradual and smoother buildup of PI was observed. When participants were left free to choose their presentation schedule, they spontaneously adopted an interleaved schedule, resulting again in more gradual PI. After longer delays, we observed recency effects at the list level in overall recall and, in the blocked condition, PI-related effects. The overall pattern of findings agrees with the predictions of the temporal discrimination theory of PI, complemented with categorical processing of list items, but not with alternative accounts, shedding light on the dynamics and underpinnings of PI under diverse presentation schedules and over different time scales.