Single-dose effects of methylphenidate and atomoxetine on functional connectivity during an n-back task in boys with ADHD.

RATIONALE: Working memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and atomoxetine improve working memory performance and increase activation of regions under-functioning in ADHD. Additionally, methylphenidate has been observed to modulate functional networks involved in working memory. No research, however, has examined the effects of atomoxetine or compared the two drugs. OBJECTIVES: This study aimed to test methylphenidate and atomoxetine effects on functional connectivity during working memory in boys with ADHD. METHODS: We tested comparative effects of methylphenidate and atomoxetine on functional connectivity during the n-back task in 19 medication-naïve boys with ADHD (10-15 years old) relative to placebo and assessed potential normalisation effects of brain dysfunctions under placebo relative to 20 age-matched neurotypical boys. Patients were scanned in a randomised, double-blind, cross-over design under single doses of methylphenidate, atomoxetine, and placebo. Controls were scanned once, unmedicated. RESULTS: Patients under placebo showed abnormally increased connectivity between right superior parietal gyrus (rSPG) and left central operculum/insula. This hyperconnectivity was not observed when patients were under methylphenidate or atomoxetine. Furthermore, under methylphenidate, patients showed increased connectivity relative to controls between right middle frontal gyrus (rMFG) and cingulo-temporo-parietal and striato-thalamic regions, and between rSPG and cingulo-parietal areas. Interrogating these networks within patients revealed increased connectivity between both rMFG and rSPG and right supramarginal gyrus under methylphenidate relative to placebo. Nonetheless, no differences across drug conditions were observed within patients at whole brain level. No drug effects on performance were observed. CONCLUSIONS: This study shows shared modulating effects of methylphenidate and atomoxetine on parieto-insular connectivity but exclusive effects of methylphenidate on connectivity increases in fronto-temporo-parietal and fronto-striato-thalamic networks in ADHD.

Reduced inferior fronto-insular-thalamic activation during failed inhibition in young adults with combined ASD and ADHD compared to typically developing and pure disorder groups.

Autism spectrum disorder (ASD) often co-occurs with attention-deficit/hyperactivity disorder (ADHD) and people with these conditions have frontostriatal functional atypicality during motor inhibition. We compared the neural and neurocognitive correlates of motor inhibition and performance monitoring in young adult males with "pure" and combined presentations with age-and sex-matched typically developing controls, to explore shared or disorder-specific atypicality. Males aged 20-27 years with typical development (TD; n = 22), ASD (n = 21), combined diagnoses ASD + ADHD (n = 23), and ADHD (n = 25) were compared using a modified tracking fMRI stop-signal task that measures motor inhibition and performance monitoring while controlling for selective attention. In addition, they performed a behavioural go/no-go task outside the scanner. While groups did not differ behaviourally during successful stop trials, the ASD + ADHD group relative to other groups had underactivation in typical performance monitoring regions of bilateral anterior insula/inferior frontal gyrus, right posterior thalamus, and right middle temporal gyrus/hippocampus during failed inhibition, which was associated with increased stop-signal reaction time. In the behavioural go/no-go task, both ADHD groups, with and without ASD, had significantly lower motor inhibition performance compared to TD controls. In conclusion, only young adult males with ASD + ADHD had neurofunctional atypicality in brain regions associated with performance monitoring, while inhibition difficulties on go/no-go task performance was shared with ADHD. The suggests that young people with ASD + ADHD are most severely impaired during motor inhibition tasks compared to ASD and ADHD but do not reflect a combination of the difficulties associated with the pure disorders.

Task-Based Functional Connectivity in Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Altered neurocognitive functioning is a key feature of attention-deficit/hyperactivity disorder (ADHD), and increasing numbers of studies assess task-based functional connectivity in the disorder. We systematically reviewed and critically appraised functional magnetic resonance imaging (fMRI) task-based functional connectivity studies in ADHD. A systematic search conducted up to September 2020 found 34 studies, including 51 comparisons. Comparisons were divided into investigations of ADHD neuropathology (37 comparing ADHD and typical development, 2 comparing individuals with ADHD and their nonsymptomatic siblings, 2 comparing remitted and persistent ADHD, and 1 exploring ADHD symptom severity) and the effects of interventions (8 investigations of stimulant effects and 1 study of fMRI neurofeedback). Large heterogeneity in study methodologies prevented a meta-analysis; thus, the data were summarized as a narrative synthesis. Across cognitive domains, functional connectivity in the cingulo-opercular, sensorimotor, visual, subcortical, and executive control networks in ADHD consistently differed from neurotypical populations. Furthermore, literature comparing individuals with ADHD and their nonsymptomatic siblings as well as adults with ADHD and their remitted peers showed ADHD-related abnormalities in similar sensorimotor and subcortical (primarily striatal) networks. Interventions modulated those dysfunctional networks, with the most consistent action on functional connections with the striatum, anterior cingulate cortex, occipital regions, and midline default mode network structures. Although methodological issues limited many of the reviewed studies, the use of task-based functional connectivity approaches has the potential to broaden the understanding of the neural underpinnings of ADHD and the mechanisms of action of ADHD treatments.

Differential Brain Perfusion Changes Following Two Mind-Body Interventions for Fibromyalgia Patients: an Arterial Spin Labelling fMRI Study.

OBJECTIVES: Further mechanistic insight on mind-body techniques for fibromyalgia (FMS) is needed. Arterial spin labelling (ASL) imaging can capture changes in regional cerebral blood flow (rCBF) that relate to spontaneous pain. METHODS: We recruited FMS patients undergoing either mindfulness-based stress reduction training (MBSR, n = 14) or a psychoeducational programme (FibroQoL, n = 18), and a control FMS group with no add-on treatment (n = 14). We acquired whole-brain rCBF maps and self-report measures at baseline and following treatment and explored interaction effects in brain perfusion between the treatment group and session with a focus on the amygdala, the insula and the anterior cingulate cortex (ACC). RESULTS: We identified a significant interaction effect in the amygdala, which corresponded with rCBF decreases following FibroQoL specifically. At baseline, rCBF in the amygdala for the FibroQoL group correlated with pain catastrophizing and anxiety scores, but not after treatment, suggesting a decoupling between activity in the amygdala and negative emotional symptoms of FMS as a consequence of treatment. Baseline rCBF correlated positively with pain symptoms in the ACC and the anterior insula across all patients; moreover, the correlation between rCBF changes post intervention in the insula and pain improvement was negative for both treatments and significantly different from the control group. We suggest that there is disruption of the typical relationship between clinical pain and activity as a product of these two nonpharmacological therapies. CONCLUSIONS: We have demonstrated that different mind-to-body treatments correspond to differential changes in clinical symptoms and brain activity patterns, which encourages future research investigating predictors of treatment response. TRIAL REGISTRATION:  NCT02561416. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12671-021-01806-2.

A pilot study exploring the effect of repetitive transcranial magnetic stimulation (rTMS) treatment on cerebral blood flow and its relation to clinical outcomes in severe enduring anorexia nervosa.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN), but associated neurobiological changes are poorly understood. This study investigated the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. METHODS: As part of a randomised sham-controlled feasibility trial of 20 sessions of high-frequency rTMS to the left dorsolateral prefrontal cortex, 26 of 34 trial participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) to quantify regional and global resting state CBF before (pre-randomisation baseline) and after real or sham treatment (1-month post-randomisation). A group of healthy females (n = 30) were recruited for baseline comparison. Clinical outcomes, including BMI, and depression and anxiety symptoms, were assessed at baseline, 1-, 4-, and 18-months post-randomisation. RESULTS: No group differences in regional CBF were identified between the SE-AN and healthy comparison participants. A significant treatment-by-time interaction in a medial temporal lobe cluster with the maximal peak in the right amygdala was identified, reflecting a greater reduction in amygdala CBF following real rTMS compared to sham. Participants with the greatest rTMS-related reduction in amygdala CBF (i.e., between baseline and 1-month post-randomisation) showed the greatest sustained weight gain at 18-months post-randomisation. Higher baseline CBF in the insula predicted greater weight gain between baseline and 1-month post-randomisation and between baseline and 4-months post-randomisation. CONCLUSIONS: This exploratory pilot study identified rTMS treatment related changes in CBF in adults with SE-AN and these were associated with changes in weight. Our preliminary findings also suggest that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should employ longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment. TRIAL REGISTRATION: ISRCTN14329415 , registered 23rd July 2015.

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN). However, little is known about the neurobiological effects of this treatment. This study explored the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. Participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) before and after receiving 20 sessions (over 4 weeks) of real or sham rTMS. We found a greater reduction in amygdala CBF following real rTMS compared to sham rTMS. Participants with the greatest rTMS-related reduction in amygdala CBF showed the greatest sustained weight gain at an 18-month follow-up. Higher baseline CBF in the insula predicted greater weight gain during treatment and at a 4-month follow-up. This suggests that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should use longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment.

Neural Correlates of Theory of Mind in Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, and the Comorbid Condition.

Theory of mind (ToM) or mentalizing difficulties is reported in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), but the mechanism underpinning these apparently shared deficits is relatively unknown. Eighty-three young adult males, 19 with ASD alone, 21 with ADHD alone, 18 with dual diagnosis of ASD and ADHD, and 25 typically developing (TD) controls completed the functional magnetic resonance imaging version of the Frith-Happé animated-triangle ToM task. We compared neural function during ToM with two non-ToM conditions, random and goal directed motions, using whole-brain and region-of-interest analysis of brain activation and functional connectivity analyses. The groups showed comparable ToM task performance. All three clinical groups lacked local connectivity increase shown by TD controls during ToM in the right temporoparietal cortex, a key mentalizing region, with a differentially increased activation pattern in both ASD and comorbid groups relative to ADHD. Both ASD groups also showed reduced connectivity between right inferior lateral prefrontal and posterior cingulate cortices that could reflect an atypical information transmission to the mentalizing network. In contrast, with mentalizing both ADHD groups showed decreasing connectivity between the medial prefrontal and left temporoparietal cortices when compared to TD controls. Therefore, despite the complex pattern of atypical brain function underpinning ToM across the three disorders, some neurofunctional abnormalities during ToM are associated with ASD and appeared differentiable from those associated with ADHD, with the comorbid group displaying combined abnormalities found in each condition.

Food related attention bias modification training for anorexia nervosa and its potential underpinning mechanisms.

Treatment outcomes in anorexia nervosa (AN) remain suboptimal, evidencing the need for better and more targeted treatments. Whilst the aetiology of AN is complex, cognitive processes such as attention bias (AB) have been proposed to contribute to maintaining food restriction behaviour. Attention bias modification raining (ABMT) has been investigated in other eating disorders (EDs) such as binge eating disorder (BED) as a means of modifying AB for food and of changing eating behaviour. Promising findings have been reported, but the mechanisms underlying ABMT are poorly understood. We hypothesise that in AN, ABMT has the potential to modify maladaptive eating behaviours related to anxiety around food and eating and propose two mechanistic models; (1) ABMT increases general attentional control (which will improve control over disorder-relevant thoughts) or (2) ABMT promotes stimulus re-evaluation. In this second case, the effects of ABMT might arise via changes in the subjective value of food stimuli (i.e. reward processing) or via habituation, with both resulting in a reduced threat response. Investigating the clinical potential of ABMT in AN holds the promise of a novel, evidence-based adjunctive treatment approach. Importantly, understanding ABMT's underlying mechanisms will help tailor treatment protocols and improve understanding of the cognitive characteristics of AN and other EDs.

Correction: Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala.

[This corrects the article DOI: 10.1371/journal.pone.0093955.].

Neural Correlates of Failed Inhibitory Control as an Early Marker of Disordered Eating in Adolescents.

BACKGROUND: Binge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB. METHODS: The study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172). RESULTS: At baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers. CONCLUSIONS: Greater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes.

Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms.

Objectives: Intragastric bitter tastants may decrease appetite and food intake. We aimed to investigate the gut-brain signaling and brain mechanisms underlying these effects.Methods: Brain responses to intragastric quinine-hydrochloride (QHCl, 10 µmol/kg) or placebo infusion were recorded using functional magnetic resonance imaging in 15 healthy women. Appetite-related sensations, plasma levels of gastrointestinal hormones and hedonic food intake (ad libitum drink test) were assessed.Results: Lower octanoylated ghrelin (P<0.04), total ghrelin (P<0.01), and motilin (P<0.01) plasma levels were found after QHCl administration, along with lower prospective food consumption ratings (P<0.02) and hedonic food intake (P<0.05). QHCl increased neural activity in the hypothalamus and hedonic (anterior insula, putamen, caudate, pallidum, amygdala, anterior cingulate cortex, orbitofrontal cortex, midbrain) regions, but decreased activity in the homeostatic medulla (all pFWE-corrected<0.05). Differential brain responses to QHCl versus placebo covaried with subjective and hormonal responses and predicted differences in hedonic food intake.Discussion: Intragastric QHCl decreases prospective and actual food intake in healthy women by interfering with homeostatic and hedonic brain circuits in a ghrelin- and motilin-mediated fashion. These findings suggest a potential of bitter tastants to reduce appetite and food intake, through the gut-brain axis.

Neural Correlates of Duration Discrimination in Young Adults with Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder and Their Comorbid Presentation.

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often co-occur and share neurocognitive deficits. One such shared impairment is in duration discrimination. However, no studies using functional magnetic resonance imaging (fMRI) have investigated whether these duration discrimination deficits are underpinned by the same or different underlying neurofunctional processes. In this study, we used fMRI to compare the neurofunctional correlates of duration discrimination between young adult males with ASD (n = 23), ADHD (n = 25), the comorbid condition of ASD+ADHD (n = 24), and typical development (TD, n = 26) using both region of interest (ROI) and whole brain analyses. Both the ROI and the whole-brain analyses showed that the comorbid ASD+ADHD group compared to controls, and for the ROI analysis relative to the other patient groups, had significant under-activation in right inferior frontal cortex (IFG) a key region for duration discrimination that is typically under-activated in boys with ADHD. The findings show that in young adult males with pure ASD, pure ADHD and comorbid ASD+ADHD with no intellectual disability, only the comorbid group demonstrates neurofunctional deficits in a typical duration discrimination region.

Randomised controlled feasibility trial of real versus sham repetitive transcranial magnetic stimulation treatment in adults with severe and enduring anorexia nervosa: the TIARA study.

OBJECTIVE: Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromodulation is a promising emerging intervention. Our study is a feasibility randomised controlled trial of repetitive transcranial magnetic stimulation (rTMS) in individuals with SE-AN, which aims to inform the design of a future large-scale trial. DESIGN: Double-blind, parallel group, two-arm, sham-controlled trial. SETTING: Specialist eating disorders centre. PARTICIPANTS: Community-dwelling people with anorexia nervosa, an illness duration of ≥3 years and at least one previous completed treatment. INTERVENTIONS: Participants received 20 sessions (administered over 4 weeks) of MRI-guided real or sham high-frequency rTMS to the left dorsolateral prefrontal cortex in addition to treatment-as-usual. OUTCOMES: Primary outcomes were recruitment, attendance and retention rates. Secondary outcomes included body mass index (BMI), eating disorder symptoms, mood, quality of life and rTMS safety and tolerability. Assessments were conducted at baseline, post-treatment and follow-up (ie, at 0 month, 1 month and 4 months post-randomisation). RESULTS: Thirty-four participants (17 per group) were randomly allocated to real or sham rTMS. One participant per group was withdrawn prior to the intervention due to safety concerns. Two participants (both receiving sham) did not complete the treatment. rTMS was safe and well tolerated. Between-group effect sizes of change scores (baseline to follow-up) were small for BMI (d=0.2, 95% CI -0.49 to 0.90) and eating disorder symptoms (d=0.1, 95% CI -0.60 to 0.79), medium for quality of life and moderate to large (d=0.61 to 1.0) for mood outcomes, all favouring rTMS over sham. CONCLUSIONS: The treatment protocol is feasible and acceptable to participants. Outcomes provide preliminary evidence for the therapeutic potential of rTMS in SE-AN. Largest effects were observed on variables assessing mood. This study supports the need for a larger confirmatory trial to evaluate the effectiveness of multi-session rTMS in SE-AN. Future studies should include a longer follow-up period and an assessment of cost-effectiveness. TRIAL REGISTRATION NUMBER: ISRCTN14329415; Pre-results.

Tracking emotions in the brain - Revisiting the Empathic Accuracy Task.

Many empathy tasks lack ecological validity due to their use of simplistic stimuli and static analytical approaches. Empathic accuracy tasks overcome these limitations by using autobiographical emotional video clips. Usually, a single measure of empathic accuracy is computed by correlating the participants' continuous ratings of the narrator's emotional state with the narrator's own ratings. In this study, we validated a modified empathic accuracy task. A valence-independent rating of the narrator's emotional intensity was added to provide comparability between videos portraying different primary emotions and to explore changes in neural activity related to variations in emotional intensity over time. We also added a new neutral control condition to investigate general emotional processing. In the scanner, 34 healthy participants watched 6 video clips of people talking about an autobiographical event (2 sad, 2 happy and 2 neutral clips) while continuously rating the narrator's emotional intensity. Fluctuation in perceived emotional intensity correlated with activity in brain regions previously implicated in cognitive empathy (bilateral superior temporal sulcus, temporoparietal junction, and temporal pole) and affective empathy (right anterior insula and inferior frontal gyrus). When emotional video clips were compared to neutral video clips, we observed higher activity in similar brain regions. Empathic accuracy, on the other hand, was only positively related to activation in regions that have been implicated in cognitive empathy. Our modified empathic accuracy task provides a new method for studying the underlying components and dynamic processes involved in empathy. While the task elicited both cognitive and affective empathy, successful tracking of others' emotions relied predominantly on the cognitive components of empathy. The fMRI data analysis techniques developed here may prove valuable in characterising the neural basis of empathic difficulties observed across a range of psychiatric conditions.

Proactive and reactive inhibitory control in eating disorders.

Altered inhibitory control has been implicated in the development and maintenance of eating disorders (ED), however it is unclear how different types of inhibitory control are affected across the EDs. We explored whether individuals with bulimia nervosa (BN), binge eating disorder (BED) and anorexia nervosa (AN) differed from healthy individuals (HC) on two types of motor inhibitory control: proactive inhibition (related to the preparation/initiation of a response) and reactive inhibition (withholding a response in reaction to a signal). Ninety-four women (28 AN, 27 BN, 11 BED, 28 HC) completed two neuropsychological tasks (a cued reaction time task and a stop signal task), and questionnaires assessing clinical variables, mood, anxiety, and inhibitory control. Self-reported inhibitory control was poorer in women with BN compared to the HC and AN groups, but greater in women with AN compared to all other groups. However, no group differences in reactive inhibition were observed. Proactive inhibition was augmented in women with AN compared to HC, and this was related to self-reported intolerance of uncertainty. The findings suggest that proactive inhibition may be a relevant target for behavioural interventions for AN, and call for further research into the relationship between intolerance of uncertainty and proactive inhibition.

Temporal Discounting and the Tendency to Delay Gratification across the Eating Disorder Spectrum.

Bulimia nervosa (BN) and binge eating disorder (BED) have been associated with poorer reward-related inhibitory control, reflected by a reduced tendency to delay gratification. The opposite has been reported in anorexia nervosa (AN), but differences have not been directly compared across eating disorders (EDs). This study investigated self-reported (Delaying Gratification Inventory) and task-based (temporal discounting) inhibitory control in 66 women with an ED and 28 healthy controls (HCs). Poorer task-based inhibitory control was observed in the BN compared with the AN group and poorer self-reported inhibitory control in the BN and in the BED groups compared with the AN and the HC groups, suggesting that reward-related inhibitory control varies across EDs. Symptom severity correlated with poorer self-reported (but not task-based) inhibitory control across the EDs. These data provide some support for transdiagnostic mechanisms and highlight the importance of addressing perceived loss of control in the treatment of EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Identifying disordered eating behaviours in adolescents: how do parent and adolescent reports differ by sex and age?

This study investigated the prevalence of disordered eating cognitions and behaviours across mid-adolescence in a large European sample, and explored the extent to which prevalence ratings were affected by informant (parent/adolescent), or the sex or age of the adolescent. The Development and Well-Being Assessment was completed by parent-adolescent dyads at age 14 (n = 2225) and again at age 16 (n = 1607) to explore the prevalence of 7 eating disorder symptoms (binge eating, purging, fear of weight gain, distress over shape/weight, avoidance of fattening foods, food restriction, and exercise for weight loss). Informant agreement was assessed using kappa coefficients. Generalised estimating equations were performed to explore the impact of age, sex and informant on symptom prevalence. Slight to fair agreement was observed between parent and adolescent reports (kappa estimates between 0.045 and 0.318); however, this was largely driven by agreement on the absence of behaviours. Disordered eating behaviours were more consistently endorsed amongst girls compared to boys (odds ratios: 2.96-5.90) and by adolescents compared to their parents (odds ratios: 2.71-9.05). Our data are consistent with previous findings in epidemiological studies. The findings suggest that sex-related differences in the prevalence of disordered eating behaviour are established by mid-adolescence. The greater prevalence rates obtained from adolescent compared to parent reports may be due to the secretive nature of the behaviours and/or lack of awareness by parents. If adolescent reports are overlooked, the disordered behaviour may have a greater opportunity to become more entrenched.

Proactive inhibition: An element of inhibitory control in eating disorders.

The aetiology of eating disorders (EDs) is unclear, but many hypotheses implicate alterations in behavioural control. Specifically and because of its relevance to symptomatology, there has been much interest in inhibitory control, i.e., the ability to inhibit inappropriate/unwanted behaviours. This has been studied in relation to reactive motor inhibition (withholding a response in reaction to a signal), reward-based inhibition (e.g., temporal discounting paradigms) and to reversal learning (e.g., set shifting tasks assessing cognitive flexibility and compulsivity). However, there has been less explicit exploration of proactive inhibitory control, i.e., a preparatory form of inhibitory control where responses are pre-emptively suppressed to improve performance either in terms of a dynamic strategy (e.g., post-error slowing) or as a more general suppression in the context of uncertainty (e.g., when the appropriateness of a response is less certain). This review considers proactive inhibition within the context of broader conceptual considerations of inhibitory control in EDs, discusses the existing behavioural and neural evidence, and concludes that this is a construct worthy of further exploration.

Task-Based and Questionnaire Measures of Inhibitory Control Are Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in Healthy Adults.

Adaptive eating behaviors are dependent on an interaction between motivational states (e.g., hunger) and the ability to control one's own behavior (inhibitory control). Indeed, behavioral paradigms are emerging that seek to train inhibitory control to improve eating behavior. However, inhibitory control is a multifaceted concept, and it is not yet clear how different types (e.g., reactive motor inhibition, proactive motor inhibition, reward-related inhibition) are affected by hunger. Such knowledge will provide insight into the contexts in which behavioral training paradigms would be most effective. The present study explored the impact of promoting a "need" state (hunger) together with motivationally salient distracting stimuli (food/non-food images) on inhibitory control in 46 healthy adults. Participants attended two study sessions, once after eating breakfast as usual and once after acute food restriction on the morning of the session. In each session, participants completed questionnaires on hunger, mood and inhibitory control, and undertook task-based measures of inhibitory control, and had physiological measurements (height, weight, and blood glucose) obtained by a researcher. Acute food restriction influenced task-based assessments but not questionnaire measures of inhibitory control, suggesting that hunger affects observable behavioral control but not self-reported inhibitory control. After acute food restriction, participants showed greater temporal discounting (devaluation of future rewards), and subjective hunger and these were inversely correlated with stop accuracy on the stop signal task. Finally, participants generally responded faster when food-related distractor images were presented, compared to non-food images, independent of state. This suggests that although food stimuli motivate approach behavior, stimulus relevance does not impact inhibitory control in healthy individuals, nor interact with motivational state. These findings may provide some explanation for poorer inhibitory control often reported in studies of individuals who practice restraint over eating.

Increased temporal discounting in bulimia nervosa.

OBJECTIVE: There is evidence that people with eating disorders display altered intertemporal choice behavior (the degree of preference for immediate rewards over delayed rewards). Compared to healthy controls (HC), individuals with anorexia nervosa and binge-eating disorder show decreased and increased rates of temporal discounting (TD; the devaluation of delayed rewards), respectively. This is the first study to investigate TD in people with bulimia nervosa (BN). METHOD: Thirty-nine individuals with BN (2 men) and 53 HC (9 men) completed a hypothetical monetary TD task. Over 80 binary choices, participants chose whether they would prefer to receive a smaller amount of money available immediately or a larger amount available in 3 months. Self-reported ability to delay gratification (the behavioral opposite of TD) was also measured. RESULTS: Individuals with BN showed greater TD (i.e., a preference for smaller-sooner rewards) and a decreased self-reported capacity to delay gratification relative to HC. Experimental groups did not differ in age, gender ratio, or BMI. DISCUSSION: Increased rates of TD may contribute to some of the core symptoms of BN that appear to involve making choices between immediate and delayed rewards (i.e., binge-eating and compensatory behaviors). Altered intertemporal choice behavior could therefore be a relevant target for intervention in this patient group. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1077-1081).

A systematic review of the relationship between eating, weight and inhibitory control using the stop signal task.

Altered inhibitory control (response inhibition, reward-based inhibition, cognitive inhibition, reversal learning) has been implicated in eating disorders (EDs) and obesity. It is unclear, however, how different types of inhibitory control contribute to eating and weight-control behaviours. This review evaluates the relationship between one aspect of inhibitory control (a reactive component of motor response inhibition measured by the stop signal task) and eating/weight in clinical and non-clinical populations. Sixty-two studies from 58 journal articles were included. Restrained eaters had diminished reactive inhibitory control compared to unrestrained eaters, and showed greatest benefit to their eating behaviour from manipulations of inhibitory control. Obese individuals may show less reactive inhibitory control but only in the context of food-specific inhibition or after executive resources are depleted. Of the limited studies in EDs, the majority found no impairment in reactive inhibitory control, although findings are inconsistent. Thus, altered reactive inhibitory control is related to some maladaptive eating behaviours, and hence may provide a therapeutic target for behavioural manipulations and/or neuromodulation. However, other types of inhibitory control may also contribute. Methodological and theoretical considerations are discussed.