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

Abstract 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

Clinical outcomes and neural correlates of 20 sessions of repetitive transcranial magnetic stimulation in severe and enduring anorexia nervosa (the TIARA study): study protocol for a randomised controlled feasibility trial

BACKGROUND: Anorexia nervosa (AN) is a serious mental disorder with multiple comorbidities and complications. In those with a severe and enduring form of the illness (SEED-AN), treatment responsivity is poor and the evidence base limited. Thus, there is a need for novel treatment strategies. This paper describes the theoretical background and protocol of a feasibility randomised controlled trial (RCT) of real versus sham (placebo) therapeutic repetitive transcranial magnetic stimulation (rTMS) in SEED-AN. The aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of rTMS in this group of patients, and also to assess the preliminary efficacy and neural correlates of rTMS treatment. DESIGN: Forty-four adults from the community with a DSM-5 diagnosis of AN, an illness duration >3 years and a previous course of unsuccessful treatment will be randomly allocated to receive 20 sessions of either real or sham rTMS, in a parallel group design. As this is a feasibility study, no primary outcome has been defined and a broad range of outcome variables will be examined. These include weight/body mass index (BMI), eating disorder psychopathology, other psychopathology (for example, depression, anxiety), quality of life, neuropsychological processes (such as self-regulation, attentional bias and food choice behaviour), neuroimaging measures (that is, changes in brain structure or function), tolerability and acceptability of rTMS, and additional service utilisation. The feasibility of conducting a large-scale RCT of rTMS and the appropriateness of rTMS as a treatment for SEED-AN will be evaluated through: assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up assessments). The acceptability and tolerability of the treatment will be assessed via semi-structured interviews. DISCUSSION: The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. Additionally, results from this study will provide a preliminary indication of the efficacy of rTMS treatment for AN, the neural correlates of the illness, and potential biomarkers of clinical response. TRIAL REGISTRATION: ISRCTN14329415. Date of registration: 23 July 2015. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-1069-3) contains supplementary material, which is available to authorized users

Significant Group × Session interaction (p<0.05, corrected) during the anticipation phase of our gambling task (left panel).

<p>To illustrate the nature of the interaction effect, the middle panel shows parameter estimates (in the order placebo at scan 1, placebo at scan 2, AS at scan 1 (before sensitisation), AS at scan 2 (after sensitisation) from the mean response within an associative striatal ROI. The graph on the right shows the correlation between sensitisation-related change in striatal BOLD signal during anticipation and the change in subjective response to amphetamine. All parameter estimates reflect the mean response in arbitrary BOLD units. Results are shown with the standard error of the mean.</p

Upper Panel: Brain regions identified as displaying sensitivity to the task phases (i.e. decision, anticipation, wins and losses) in the placebo group (left panel).

<p>Parameter estimates for key dopaminergic and reward-related areas showing a significant main effect of task (right panel). Lower Panel: Brain regions where BOLD signal was modulated by reward probability the placebo group (left panel). Parameter estimates from the occipital cortex and precuneus, regions that display a significant main effect of reward probability. All parameter estimates reflect the mean response in arbitrary BOLD units. Results are shown with the standard error of the mean.</p

Exploring psychotic symptoms:a comparison of motor related neuronal activation during and after acute psychosis

BACKGROUND: Delusions and hallucinations are classic positive symptoms of schizophrenia. A contemporary cognitive theory called the ‘forward output model’ suggests that the misattribution of self-generated actions may underlie some of these types of symptoms, such as delusions of control – the experience of self-generated action being controlled by an external agency. In order to examine the validity of this suggestion, we performed a longitudinal functional magnetic resonance imaging (fMRI) study examining neuronal activation associated with motor movement during acute psychosis. METHODS: We studied brain activation using fMRI during a motor task in 11 patients with schizophrenia and 9 healthy controls. The patient group was tested at two time points separated by 6–8 weeks. RESULTS: At initial testing, the patient group had a mean Positive and Negative Syndrome Scale score of 56.3, and showed significantly increased activation within the left inferior parietal lobe (IPL) compared to controls. Patients reported significantly decreased positive symptoms at 6–8 week followup and IPL activation had returned to normal. Our results demonstrate that first-rank positive symptoms are associated with hyperactivation in the secondary somatosensory cortex (IPL). CONCLUSIONS: These findings lend further credence to the theory that a dysfunction in the sensory feedback system located in the IPL, and which is thought to underlie our sense of agency, may contribute to the aetiology of delusions of control

A link between FTO, ghrelin, and impaired brain food-cue responsivity

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