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Background: There is a need for improved understanding of why 20–30% of individuals with anorexia nervosa (AN) develop a severe and enduring form of illness (SE-AN). Previously, we reported differences in proactive inhibition (a pre-emptive slowing of responses) in individuals with AN compared to healthy controls (after controlling for intolerance of uncertainty). The present study is a preliminary exploration of proactive inhibition in which we compared women with SE-AN with healthy comparison (HC) women and explored its association with restrictive/avoidant eating behaviours. Methods: Thirty-four women with SE-AN (defined by >3 years of illness and a previous unsuccessful course of eating disorder treatment) and 30 HCs completed (a) a cued reaction time task, to assess proactive inhibition, and (b) questionnaires assessing restrictive/avoidant eating behaviours and intolerance of uncertainty. Results: Both SE-AN and HC participants showed slower reaction times under conditions of uncertainty, indicating proactive inhibition in both groups. There was a main effect of group, with SE-AN participants showing significantly slower reaction times compared to HC. There was no interaction between group and condition, suggesting that individuals with SE-AN did not differ in proactive inhibition compared to HCs. However, post-hoc analysis between-group tests for each trial type revealed that group differences were only present under conditions of uncertainty. Proactive inhibition was not significantly associated with self-reported restrictive/avoidant eating behaviours, including when taking intolerance of uncertainty into consideration. Conclusions: It is unlikely that proactive inhibition contributes to avoidant and restrictive eating behaviours seen in SE-AN. Our findings suggest that the SE-AN group are relatively more cautious when responding under conditions of uncertainty. Longitudinal studies and between-group comparisons of individuals across different stages of illness will be required to elucidate the way in which proactive inhibition is specifically implicated in SE-AN, rather than in AN more generally. Plain English Summary: Proactive inhibition refers to the pre-emptive slowing of responses. We assessed whether 34 women with severe and enduring anorexia nervosa (defined by greater than 3 years of illness and a previous unsuccessful course of treatment) differed from 30 healthy comparison women in proactive inhibition. We also explored if proactive inhibition was related to restrictive eating behaviours. All participants completed a cued reaction time task to assess proactive inhibition and questionnaires assessing restrictive/avoidant eating behaviours and intolerance of uncertainty. All participants showed proactive inhibition, i.e., slower reaction times under conditions of uncertainty. Participants with severe and enduring anorexia nervosa showed significantly slower reaction times compared to healthy comparison women. Proactive inhibition was not significantly associated with self-reported restrictive/avoidant eating behaviours. Our findings suggest that compared to the healthy comparison group of women, the severe and enduring anorexia nervosa group are more cautious when responding, specifically in the context of uncertainty. It is unlikely that proactive inhibition contributes to avoidant and restrictive eating behaviours in severe and enduring anorexia nervosa. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the huntingtin gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. Objective: In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression. Methods: Following MRI optimization in five healthy volunteers (cohort 1), we aim to recruit 108 participants of whom 72 are people with HD (PwHD) and 36 healthy volunteers (cohort 2). Pending interim analysis, these numbers could increase to 96 PwHD and 48 healthy controls. Participants will complete a total of 10 study visits, consisting of a screening visit followed by a clinical and MRI visit and PET visits at baseline, year 1, and year 2. PET targets include the cannabinoid 1, histamine 3, and serotonin 2A receptors, and phosphodiesterase 10A, whereas MRI will be multimodal, including, but not limited to, the assessment of cerebral blood flow, functional connectivity, and brain iron. Results: Recruitment is currently active and started in September 2022. Conclusions: By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Mind-body treatments can improve coping mechanisms to deal with pain, improve the quality of life of patients with fibromyalgia syndrome (FMS), and reduce perceived pain in some cases. However, responses to these treatments are highly variable, the mechanisms underpinning them remain unclear, and reliable predictors of treatment response are lacking. We employed resting-state blood oxygen level-dependent (rsBOLD) functional magnetic resonance imaging (fMRI) to examine changes in brain functional connectivity (FC) following mind-body treatment that may relate to and predict pain relief. Methods: We recruited patients with FMS who underwent either mindfulnessbased stress reduction (MBSR; n = 18) or a psychoeducational program (FibroQoL; n = 22) and a treatment-as-usual FMS group (TAU; n = 18). We collected rsBOLD data, alongside subjective pain, anxiety, depression, and catastrophizing measures prior to and following treatments. We examined behavioral changes and FC changes in the salience network (SN) and sensorimotor network (SMN) and performed regression analyses to identify predictors for treatment response. Results: The MBSR and FibroQoL groups experienced significant reductions in pain catastrophizing. After treatment, the FC of the sensorimotor cortex with the rest of the SMN became significantly reduced in the MBSR group compared to the TAU group. The FC between the SN and the SMN at baseline was negatively correlated with pain reductions following MBSR but positively correlated with pain reductions in the FibroQoL group. These results yielded large to very large effect sizes. Following MBSR, only for those patients with lower baseline SMN-SN FC, minutes of mindfulness practice were positively associated with clinical improvement (small to medium effect size). Conclusions: Different mind-body treatments are underpinned by discrete brain networks. Measures of the functional interplay between SN and SMN have the potential as predictors of mind-body treatment response in patients with FMS. [ABSTRACT FROM AUTHOR]

Introduction: Startle habituation and prepulse inhibition (PPI) are distinct measures of different sensory information processes, yet both result in the attenuation of the startle reflex. Identifying startle habituation and PPI neural mechanisms in humans has mostly evolved from acoustic-focused rodent models. Human functional magnetic resonance imaging (fMRI) studies have used tactile startle paradigms to avoid the confounding effects of gradient-related acoustic noise on auditory paradigms and blood-oxygen-level-dependent (BOLD) measures. This study aimed to examine the neurofunctional basis of acoustic startle habituation and PPI in humans with silent fMRI. Methods: Using silent fMRI and simultaneous electromyography (EMG) to measure startle, the neural correlates of acoustic short-term startle habituation and PPI [stimulus onset asynchronies (SOA) of 60  ms and 120  ms] were investigated in 42 healthy adults (28 females). To derive stronger inferences about brain-behaviour correlations at the group-level, models included EMGassessed measures of startle habituation (regression slope) or PPI (percentage) as a covariate. A linear temporal modulator was modelled at the individual-level to characterise functional changes in neural activity during startle habituation. Results: Over time, participants showed a decrease in startle response (habituation), accompanied by decreasing thalamic, striatal, insula, and brainstem activity. Startle habituation was associated with the linear temporal modulation of BOLD response amplitude in several regions, with thalamus, insula, and parietal lobe activity decreasing over time, and frontal lobe, dorsal striatum, and posterior cingulate activity increasing over time. The paradigm yielded a small amount of PPI (9–13%). No significant neural activity for PPI was detected. Discussion: Startle habituation was associated with the thalamus, putamen, insula, and brainstem, and with linear BOLD response modulation in thalamic, striatal, insula, parietal, frontal, and posterior cingulate regions. These findings provide insight into the mediation and functional basis of the acoustic primary startle circuit. Instead, whilst reduced compared to conventional MRI, scanner noise may have disrupted prepulse detection and processing, resulting in low PPI and impacting our ability to map its neural signatures. Our findings encourage optimisation of the MRI environment for acoustic PPI-based investigations in humans. Combining EMG and functional neuroimaging methods shows promise for mapping short-term startle habituation in healthy and clinical populations. [ABSTRACT FROM AUTHOR]

Background: The mechanisms underlying the antipsychotic potential of cannabidiol (CBD) remain unclear but growing evidence indicates that dysfunction in the insula, a key brain region involved in the processing of motivationally salient stimuli, may have a role in the pathophysiology of psychosis. Here, we investigate whether the antipsychotic mechanisms of CBD are underpinned by their effects on insular activation, known to be involved in salience processing. Methods: A within-subject, crossover, double-blind, placebo-controlled investigation of 19 healthy controls and 15 participants with early psychosis was conducted. Administration of a single dose of CBD was compared with placebo in psychosis participants while performing the monetary incentive delay task, an fMRI paradigm. Anticipation of reward and loss were used to contrast motivationally salient stimuli against a neutral control condition. Results: No group differences in brain activation between psychosis patients compared with healthy controls were observed. Attenuation of insula activation was observed following CBD, compared to placebo. Sensitivity analyses controlling for current cannabis use history did not affect the main results. Conclusion: Our findings are in accordance with existing evidence suggesting that CBD modulates brain regions involved in salience processing. Whether such effects underlie the putative antipsychotic effects of CBD remains to be investigated. [ABSTRACT FROM AUTHOR]