Comparison of online, offline, and hybrid hypotheses of motor sequence learning using a quantitative model that incorporate reactive inhibition.

Two hypotheses have been advanced for when motor sequence learning occurs: offline between bouts of practice or online concurrently with practice. A third possibility is that learning occurs both online and offline. A complication for differentiating between those hypotheses is a process known as reactive inhibition, whereby performance worsens over consecutively executed sequences, but dissipates during breaks. We advance a new quantitative modeling framework that incorporates reactive inhibition and in which the three learning accounts can be implemented. Our results show that reactive inhibition plays a far larger role in performance than is appreciated in the literature. Across four groups of participants in which break times and correct sequences per trial were varied, the best overall fits were provided by a hybrid model. The version of the offline model that does not account for reactive inhibition, which is widely assumed in the literature, had the worst fits. We discuss implications for extant hypotheses and directions for future research.

Enhanced reactive inhibition in adolescents with non-suicidal self-injury disorder.

AIM: To investigate whether the core of the pathophysiology underlying non-suicidal self-injury (NSSI) relates to poor impulse control due to impaired motor inhibition (i.e. the ability to inhibit a preplanned motor response). METHOD: We conducted a case-control study to compare the proficiency of two domains of motor inhibition, that is, reactive and proactive inhibition, by giving the reaching arm version of the stop-signal task and a go-only task to 28 drug-naive adolescents with NSSI disorder (NSSID) (mean age [SD] 15 years 8 months [1 year 4 months]; three males and 25 females) and 28 typically developing adolescents (mean age 15 years 8 months [1 year 5 months]; three males and 25 females). RESULTS: Reactive inhibition, as determined by the duration of the stop-signal reaction time, was enhanced in adolescents with NSSID compared to typically developing controls (194.2 [22.5 ms] vs 217.5 [17.3 ms], p < 0.001). By contrast, proactive inhibition was similar in both groups. Lastly, the level of impulsivity, assessed using the Barratt Impulsiveness Scale Version 11, did not differ between typically developing adolescents and adolescents with NSSID. However, adolescents with NSSID were more impulsive than controls in a subscale of the UPPS-P Impulsive Behavior Scale. INTERPRETATION: NSSID is not driven by heightened motor impulsivity. Instead, adolescents with NSSID exhibited greater proficiency in reactive inhibition, a proxy for motor impulsivity. We suggest that the enhancement of reactive inhibition strengthens action control, allowing adolescents to suppress their self-protection instinct and perform NSSI behaviours.

Imbalanced weighting of proactive and reactive control as a marker of risk-taking propensity.

According to the dual mechanisms of control (DMC), reactive and proactive control are involved in adjusting behaviors when maladapted to the environment. However, both contextual and inter-individual factors increase the weight of one control mechanism over the other, by influencing their cognitive costs. According to one of the DMC postulates, limited reactive control capacities should be counterbalanced by greater proactive control to ensure control efficiency. Moreover, as the flexible weighting between reactive and proactive control is key for adaptive behaviors, we expected that maladaptive behaviors, such as risk-taking, would be characterized by an absence of such counterbalance. However, to our knowledge, no studies have yet investigated this postulate. In the current study, we analyzed the performances of 176 participants on two reaction time tasks (Simon and Stop Signal tasks) and a risk-taking assessment (Balloon Analog Risk Taking, BART). The post-error slowing in the Simon task was used to reflect the spontaneous individuals' tendency to proactively adjust behaviors after an error. The Stop Signal Reaction Time was used to assess reactive inhibition capacities and the duration of the button press in the BART was used as an index of risk-taking propensity. Results showed that poorer reactive inhibition capacities predicted greater proactive adjustments after an error. Furthermore, the higher the risk-taking propensity, the less reactive inhibition capacities predicted proactive behavioral adjustments. The reported results suggest that higher risk-taking is associated with a smaller weighting of proactive control in response to limited reactive inhibition capacities. These findings highlight the importance of considering the imbalanced weighting of reactive and proactive control in the analysis of risk-taking, and in a broader sense, maladaptive behaviors.

Proactive and reactive response inhibition of individuals with high schizotypy viewing different facial expressions: An ERP study using an emotional stop-signal task.

The present study aimed to examine whether impairments in reactive (outright stopping) and proactive (preparation for stopping) response inhibition are affected by negative emotions in individuals with high schizotypy, a subclinical group at risk for schizophrenia, as well as the neural mechanisms underlying these processes. Twenty-seven participants with high schizotypy and 28 matched low-schizotypy individuals completed an emotional stop-signal task in which they responded to facial emotions (neutral or angry) or inhibited their responses (when the frame of the picture turned red). Electroencephalogram (EEG) data were also recorded during the task. At the neural level, analysis of go trials revealed that viewing angry faces impaired proactive inhibition. In addition, the high-schizotypy group exhibited a greater P3 amplitude in go trials in the neutral condition than the low-schizotypy group; however, no group difference was found in the angry condition. For stop trials (reactive inhibition), a smaller P3 amplitude was found in the angry condition than in the neutral condition. Moreover, high-schizotypy individuals showed smaller P3 amplitudes than low-schizotypy individuals. The current findings suggest that, at the neural level, viewing negative emotions impaired both proactive and reactive response inhibition. Individuals with high schizotypy exhibited impairments in proactive response inhibition in the neutral condition but not in the angry condition; they exhibited impaired reactive response inhibition in both emotion conditions. The present findings deepen our understanding of emotional response inhibition in individuals on the schizophrenia spectrum.

Prepared and reactive inhibition in smokers and non-smokers.

INTRODUCTION: Models of addiction have identified deficits in inhibitory control, or the ability to inhibit inappropriate or unwanted behaviors, as one factor in the development and maintenance of addictive behaviors. Current literature supports disruption of the prefrontal circuits that mediate reactive inhibitory control processes (i.e., inhibition in response to sudden, unplanned changes in environmental demands) in substance use disorders. However, the relationship between disorders of addiction, such as nicotine dependence, and planned inhibitory processes (i.e., inhibition that occurs after advance warning) is unclear. The goal of the present study was to examine the extent to which reactive and planned inhibitory processes are differentially disrupted in nicotine dependent individuals. METHOD: We employed an internet-based novel stop signal task wherein participants were instructed to stop a continuous movement at either a predictable or unpredictable time. This task explicitly separated planned and reactive inhibitory processes and assessed group differences in task performance between smokers (N = 281) and non-smokers (N = 164). The smoker group was defined as any participant that identified as a smoker and reported an average daily nicotine consumption of at least 2 mg. The non-smoker group was defined as any participant that identified as a non-smoker and had not been a former smoker that quit within the last year. The smoker group also completed a questionnaire regarding smoking behaviors which included the Fägerstrom Test of Nicotine Dependence (FTND). We used these data to assess the continuous relation between planned stopping, unplanned stopping, and smoking behaviors. RESULTS: We found significant differences in stop times for both reactive and planned stopping between groups as well as within the smoker group. Additionally, in the smoker group, dependence as measured by the FTND was associated with longer stop times on planned stop trials. Surprisingly, greater daily average consumption of nicotine was related to faster stopping for both trial types. CONCLUSION: These results indicate the relevance of measuring both reactive and planned inhibitory processes for elucidating the relationship between nicotine addiction and mechanisms of inhibitory control.

TMS reveals distinct patterns of proactive and reactive inhibition in motor system activity.

Response inhibition is our ability to suppress or cancel actions when required. Deficits in response inhibition are linked with a range of psychopathological disorders including addiction and OCD. Studies on response inhibition have largely focused on reactive inhibition-stopping an action when explicitly cued. Less work has examined proactive inhibition-preparation to stop ahead of time. In the current experiment, we studied both reactive and proactive inhibition by adopting a two-step continuous performance task (e.g., "AX"-CPT) often used to study cognitive control. By combining a dot pattern expectancy (DPX) version of this task with transcranial magnetic stimulation (TMS), we mapped changes in reactive and proactive inhibition within the motor system. Measured using motor-evoked potentials, we found modulation of corticospinal excitability at critical timepoints during the DPX when participants were preparing in advance to inhibit a response (at step 1: during the cue) and while inhibiting a response (at step 2: during the probe). Notably, motor system activity during early timepoints was predicted by a behavioural index of proactive capacity and could predict whether participants would later successfully inhibit their response. Our findings demonstrate that combining TMS with a two-step CPT such as the DPX can be useful for studying reactive and proactive inhibition, and reveal that successful inhibition is determined earlier than previously thought.

"Free won't" of food in overweight and normal-weight adults: Comparison of neurocognitive correlates of intentional and reactive inhibitions.

Food-related inhibition plays a critical role in the manifestation of overweight. Previous research has focused exclusively on stimulus-driven (reactive) inhibition, which is different from intentional inhibition that refers to an internally generated decision to "stop". This study investigated the food-related neurophysiological correlates of intentional and reactive inhibitions in overweight and normal-weight adults. We compared 35 overweight participants (OWs) and 34 normal-weight participants (NWs) on performance and electroencephalography-based measures during a food-related go/no-go/choose task. In this task, participants made reactive responses to an instructed go/no-go target or made intentional choices whether to execute or inhibit a keypress when presented with a free-choice target. Our results mainly showed, 1) for group-difference, N2a amplitudes of OWs were less negative than that of NWs in the intentional trials; 2) for source difference, N2a amplitudes were less negative in reactive condition than in intentional condition uniquely in OWs. Moreover, comparison across intentional responses revealed that P2 amplitudes in no-go trials were lower than in go trials. Additionally, a greater body mass index correlated with lower intentional no-go-P2 and reactive go/no-go-P2 amplitudes. These findings suggest that overweight is associated with deficits in food-related intentional inhibition, which is segregated from reactive inhibition. The individual differences in premotor inhibition during free-choice situations might provide an explanation for overeating behaviors in overweight adults' daily life. Further, our results refine the ERP marker of intentional inhibition from N2 to N2a, which could be an essential neural mechanism underlying the "free won't" of food in OWs.

Early response competition over the motor cortex underlies proactive control of error correction.

Response inhibition is a fundamental brain function that must be flexible enough to incorporate proactive goal-directed demands, along with reactive, automatic and well consolidated behaviors. However, whether proactive inhibitory processes can be explained by response competition, rather than by active top-down inhibitory control, remains still unclear. Using a modified version of the Eriksen flanker task, we examined the behavioral and electrophysiological correlates elicited by manipulating the degree of inhibitory control in a task that involved the fast amendment of errors. We observed that restraining or encouraging the correction of errors did not affect the behavioral and neural correlates associated to reactive inhibition. We rather found that an early, sustained and bilateral activation, of both the correct and the incorrect response, was required for an effective proactive inhibitory control. Selective unilateral patterns of response preparation were instead associated with defective response suppression. Our results provide behavioral and electrophysiological evidence of a simultaneous dual pre-activation of two motor commands, likely underlying a global operating mechanism suggesting competition or lateral inhibition to govern the amendment of errors. These findings are consistent with the response inhibitory processes already observed in speed-accuracy tradeoff studies, and hint at a decisive role of early response competition to determine the success of multiple-choice action selection.

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.

Effects of single-session transcranial direct current stimulation on reactive response inhibition.

Transcranial direct current stimulation (tDCS) is widely used to explore the role of various cortical regions for reactive response inhibition. In recent years, tDCS studies reported polarity-, time- and stimulation-site dependent effects on response inhibition. Given the large parameter space in which study designs, tDCS procedures and task procedures can differ, it is crucial to systematically explore the existing tDCS literature to increase the current understanding of potential modulatory effects and limitations of different approaches. We performed a systematic review on the modulatory effects of tDCS on response inhibition as measured by the Stop-Signal Task. The final dataset shows a large variation in methodology and heterogeneous effects of tDCS on performance. The most consistent result across studies is a performance enhancement due to anodal tDCS over the right prefrontal cortex. Partially sub-optimal choices in study design, methodology and lacking consistency in reporting procedures may impede valid conclusions and obscured the effects of tDCS on response inhibition in some previous studies. Finally, we outline future directions and areas to improve research.

Age, Sex, and Inhibitory Control: Identifying a Specific Impairment in Memorial, But Not Perceptual, Inhibition in Older Women.

OBJECTIVES: Declines in the ability to inhibit information, and the consequences to memory of unsuccessful inhibition, have been frequently reported to increase with age. However, few studies have investigated whether sex moderates such effects. Here, we examined whether inhibitory ability may vary as a function of age and sex, and the interaction between these two factors. METHOD: 202 older (mean age = 69.40 years) and younger (mean age =30.59 years) participants who had equivalent educational attainment and self-reported health completed 2 tasks that varied only in the time point at which inhibition should occur: either prior to, or after, encoding. RESULTS: While we did not find evidence for age or sex differences in inhibitory processes when information needed to be inhibited prior to encoding, when encoded information being actively held in working memory needed to be suppressed, we found that older women were particularly impaired relative to both younger women and men of either age group. DISCUSSION: These results provide further support for the presence of memorial inhibitory deficits in older age, but add nuance by implicating biological sex as an important mediator in this relationship, with it more difficult for older women to inhibit what was once relevant in memory.

An ERP study on proactive and reactive response inhibition in individuals with schizotypy.

Schizotypy, a subclinical group at risk for schizophrenia, has been found to show impairments in response inhibition. However, it remains unclear whether this impairment is accompanied by outright stopping (reactive inhibition) or preparation for stopping (proactive inhibition). We recruited 20 schizotypy and 24 non-schizotypy individuals to perform a modified stop-signal task with electroencephalographic (EEG) data recorded. This task consists of three conditions based on the probability of stop signal: 0% (no stop trials, only go trials), 17% (17% stop trials), and 33% (33% stop trials), the conditions were indicated by the colour of go stimuli. For proactive inhibition (go trials), individuals with schizotypy exhibited significantly lesser increase in go response time (RT) as the stop signal probability increasing compared to non-schizotypy individuals. Individuals with schizotypy also exhibited significantly increased N1 amplitude on all levels of stop signal probability and increased P3 amplitude in the 17% stop condition compared with non-schizotypy individuals. For reactive inhibition (stop trials), individuals with schizotypy exhibited significantly longer stop signal reaction time (SSRT) in both 17% and 33% stop conditions and smaller N2 amplitude on stop trials in the 17% stop condition than non-schizotypy individuals. These findings suggest that individuals with schizotypy were impaired in both proactive and reactive response inhibition at behavioural and neural levels.

Prefrontal Responses during Proactive and Reactive Inhibition Are Differentially Impacted by Stress in Anorexia and Bulimia Nervosa.

Binge eating is a distressing, transdiagnostic eating disorder symptom associated with impulsivity, particularly in negative mood states. Neuroimaging studies of bulimia nervosa (BN) report reduced activity in frontostriatal regions implicated in self-regulatory control, and an influential theory posits that binge eating results from self-regulation failures under stress. However, there is no direct evidence that psychological stress impairs self-regulation in binge-eating disorders, or that any such self-regulatory deficits generalize to binge eating in underweight individuals (i.e., anorexia nervosa bingeing/purging subtype; AN-BP). We therefore determined the effect of acute stress on inhibitory control in 85 women (BN, 33 women; AN-BP, 22 women; 30 control participants). Participants underwent repeated functional MRI scanning during performance of the Stop-signal anticipation task, a validated measure of proactive (i.e., anticipation of stopping) and reactive (outright stopping) inhibition. Neural and behavioral responses to induced stress and a control task were evaluated on 2 consecutive days. Women with BN had reduced proactive inhibition, while prefrontal responses were increased in both AN-BP and BN. Reactive inhibition was neurally and behaviorally intact in both diagnostic groups. Both AN-BP and BN groups showed distinct stress-induced changes in inferior and superior frontal activity during both proactive and reactive inhibition. However, task performance was unaffected by stress. These results offer novel evidence of reduced proactive inhibition in BN, yet inhibitory control deficits did not generalize to AN-BP. Our findings identify intriguing alterations of stress responses and inhibitory function associated with binge eating, but they counsel against stress-induced failures of inhibitory control as a comprehensive explanation for loss-of-control eating.SIGNIFICANCE STATEMENT Binge eating is a common psychiatric syndrome that feels uncontrollable to the sufferer. Theoretically, it has been related to reduced self-regulation under stress, but there remains no direct evidence for this link in binge-eating disorders. Here, we examined how experimentally induced stress affected response inhibition in control participants and women with anorexia nervosa and bulimia nervosa. Participants underwent repeated brain scanning under stressful and neutral conditions. Although patient groups had intact action cancellation, the slowing of motor responses was impaired in bulimia nervosa, even when the likelihood of having to stop increased. Stress altered brain responses for both forms of inhibition in both groups, yet performance remained unimpaired. These findings counsel against a simple model of stress-induced disinhibition as an adequate explanation for binge eating.

Contiguity of proactive and reactive inhibitory brain areas: a cognitive model based on ALE meta-analyses.

Cognitive control is a critical feature in adapting our behavior to environmental and internal demands with two types of inhibition having been identified, namely the proactive and the reactive. Aiming to shed light on their respective neural correlates, we decided to focus on the cerebral activity before or after presentation of the target demanding a subject's stop as a way to separate the proactive from the reactive components associated with the tasks. Accordingly, we performed three Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies exploring proactive and reactive inhibitory phases of cognitive control. For this purpose, we searched for fMRI studies investigating brain activity preceding or following target stimuli. Eight studies (291 subjects, 101 foci) were identified for the proactive analysis. Five of these studies and those previously analyzed by others (348 subjects, 199 foci) were meta-analyzed to explore the neural correlates of reactive inhibition. Overall, our results showed different networks for the two inhibitory components. Notably, we observed a contiguity between areas in the right inferior frontal gyrus pertaining to proactive inhibition and in the right middle frontal gyrus regarding reactive inhibition. These neural correlates allow proposal of a new comprehensive model of cognitive control.

Association between lack of functional connectivity of the frontal brain region and poor response inhibition in children with frontal lobe epilepsy.

PURPOSE: We investigated the relationship between electroencephalographic (EEG) functional connectivity and executive function in children with frontal lobe epilepsy (FLE). METHODS: We enrolled 24 children with FLE (mean age, 11.0 years; 13 boys) and 22 sex-, age-, and intelligence-matched typically developing children (TDC) to undergo 19-channel EEG during light sleep. We estimated functional connectivity using the phase lag index (PLI) that captures the synchronization of EEG. We also performed continuous performance tests (CPTs) on the children and obtained questionnaire responses on attention deficit hyperactivity disorder and oppositional defiant disorder (ODD). RESULTS: The average gamma PLI was lower in the FLE group than in the TDC group, especially between long-distance frontoparietal pairs, between interhemispheric frontal pairs, and between interhemispheric parietotemporal pairs. Gamma PLIs with long-distance frontoparietal and interhemispheric frontal pairs were positively associated with inattention, ODD scores, omission error, and reaction time in the FLE group but not in the TDC group. Conversely, they were negatively associated with age, hyperactivity score, and commission error. CONCLUSIONS: A lack of functional connectivity of the frontal brain regions in children with FLE was associated with poor response inhibition.

Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia.

Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive-compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.

Comparison of Intentional Inhibition and Reactive Inhibition in Adolescents and Adults: An ERP Study.

In contrast to reactive inhibition, intentional inhibition is the internally generated decision to "stop" without any external signals. Whether adults and adolescents' neural correlates on these two inhibitions have any differences is still unknown. We measured 20 adults and 21 adolescents' ERP-related N2 using a free-choice Go/Nogo task. The results of the adult's group showed that the mean amplitude and peak latency of intentional Nogo-N2 did not differ from the reactive Nogo-N2. In contrast, the mean amplitude and peak latency for reactive Nogo-N2 in the adolescent group was significantly greater than what was observed for the intentional Nogo-N2. Comparison across groups revealed that the mean amplitude and peak latency of reactive Nogo-N2 were significantly greater in adolescents than in adults, while intentional Nogo-N2 did not differ between groups. These findings may indicate that adolescents lack of self-control is more reflected in reactive inhibition, if adolescents decide whether to do, they will be as good as adults.

Is there a proactive and a reactive mechanism of inhibition? Towards an executive account of the attentional inhibitory control model.

In cognitive neuroscience, an extensive debate concerns the mechanisms of inhibition and the relationship between inhibitory and behavioural control. Since the proactive mode of inhibition was first described, several studies have aimed to distinguish this form of inhibitory control from the reactive one. In fact, according to the dualistic models of cognitive control, the two forms of inhibition regulate the action control. However, most of the studies in this field neglected the role of attention in response inhibition, as well as the role of inhibition as an executive function. In the present article, emerging evidence in favour of a unitary mechanism of inhibition is reviewed: recent observations suggest that inhibition represents a default mode of the human brain, and that inhibitory control should not be dissociated from attentional control. Accordingly, the so-called proactive and reactive inhibition might reflect the contribution of the sustained and selective attention in the implementation of the default inhibitory control, which might be more properly termed as attentional inhibitory control (AIC). Evidence of the integrated perspective of the AIC model is reviewed from the neural, cognitive and neuropsychological point of view. Theoretical and clinical implications are discussed.

Neural correlates of proactive and reactive inhibition of saccadic eye movements.

Although research on goal-directed, proactive inhibitory control (IC) and stimulus-driven, reactive IC is growing, no previous study has compared proactive IC in conditions of uncertainty with regard to upcoming inhibition to conditions of certain upcoming IC. Therefore, we investigated effects of certainty and uncertainty on behavior and blood oxygen level dependent (BOLD) signal in proactive and reactive IC. In two studies, healthy adults performed saccadic go/no-go and prosaccade/antisaccade tasks. The certainty manipulation had a highly significant behavioral effect in both studies, with inhibitory control being more successful under certain than uncertain conditions on both tasks (p ≤ 0.001). Saccadic go responses were significantly less efficient under conditions of uncertainty than certain responding (p < 0.001). Event-related functional magnetic resonance imaging (fMRI) (one study) revealed a dissociation of certainty- and uncertainty-related proactive inhibitory neural correlates in the go/no-go task, with lateral and medial prefrontal and occipital cortex showing stronger deactivations during uncertainty than during certain upcoming inhibition, and lateral parietal cortex being activated more strongly during certain upcoming inhibition than uncertainty or certain upcoming responding. In the antisaccade task, proactive BOLD effects arose due to stronger deactivations in uncertain response conditions of both tasks and before certain prosaccades than antisaccades. Reactive inhibition-related BOLD increases occurred in inferior parietal cortex and supramarginal gyrus (SMG) in the go/no-go task only. Proactive IC may imply focusing attention on the external environment for encoding salient or alerting events as well as inhibitory mechanisms that reduce potentially distracting neural processes. SMG and inferior parietal cortex may play an important role in both proactive and reactive IC of saccades.

Enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.

Chronic pain in persons living with HIV (PLWH) may be related to alterations in endogenous pain modulatory processes (e.g., high facilitation and low inhibition of nociception) that promote exaggerated pain responses, known as hyperalgesia, and central nervous system (CNS) sensitization. This observational study examined differences in endogenous pain modulatory processes between 59 PLWH with chronic pain, 51 PLWH without chronic pain, and 50 controls without HIV or chronic pain. Quantitative sensory testing for temporal summation (TS) of mechanical and heat pain as well as conditioned pain modulation (CPM) were used to assess endogenous pain facilitatory and inhibitory processes, respectively. Associations among TS, CPM, and self-reported clinical pain severity were also examined in PLWH with chronic pain. Findings demonstrated significantly greater TS of mechanical and heat pain for PLWH with chronic pain compared to PLWH without chronic pain and controls. CPM effects were present in controls, but not in either PLWH with or without chronic pain. Among PLWH with chronic pain, greater TS of mechanical pain was significantly associated with greater average clinical pain severity. Results of this study suggest that enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.