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Background Childhood maltreatment and peer victimisation are common sources of early-life interpersonal stress. Childhood maltreatment is associated with atypical frontolimbic emotion processing and regulation, and increased vulnerability for self-harm/suicide. However, few studies have compared the neurofunctional correlates between caregiver- versus peer-inflicted mistreatment. Aims We compared the alterations of neurofunctional correlates of facial emotion processing in youths exposed to childhood maltreatment or peer victimisation, and explored their associations with self-harm. Method Functional magnetic resonance imaging data were collected from 114 age- and gender-matched youths (39 childhood maltreatment, 37 peer victimisation and 38 controls) during an emotion discrimination task. Region-of-interest (amygdala, insula) and whole-brain analyses were conducted. Results Groups differed significantly during disgust processing only. Both groups had lower activation in the right amygdala and bilateral posterior insula than controls; left insular underactivation was furthermore related to increased self-harm in maltreated youths. Compared with controls, at the whole-brain level, both groups also had underactivation in a cluster of bilateral limbic-thalamic-striatal, precuneus/posterior cingulate, temporal, fusiform/lingual and cerebellar regions, which was negatively associated with emotional problems in controls, as well as a cluster of somatosensory regions associated with increased self-harm in maltreated youths. Conclusions Early-life interpersonal stress from caregivers or peers is associated with common underactivation of limbic-thalamic-striatal, precuneus/posterior cingulate and somatosensory regions during disgust processing. The hypoactivation of key emotion and sensory processing and self-referential brain regions could be a potential suppressive mechanism to cope with the aversive emotion; however, it may also entail increased risk of affective psychopathology in seemingly healthy youths.

Abstract Background Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action. Methods A confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment. Discussion This multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD. Trial registration: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .

Abstract Background Sahaja Yoga Meditation draws on many religious traditions and uses a variety of techniques including Christian prayer to reach a state known as thoughtless awareness, or mental silence. While there are many studies on the neural correlates of meditation, few studies have focused on the neural correlates of praying. Thus, the aim of our research was to study the neural activity associated with the prayer practices in Sahaja Yoga Mediation, which have not been studied before, to explore effects beyond repetitive speech or “mantra effects”. Sixteen experienced Sahaja Yoga Meditation practitioners were scanned using task based functional Magnetic Resonance Imaging while performing formalised and improvised forms of praying and their equivalent secular tasks. Results Our results showed the deactivation of bilateral thalamus during both prayers compared to secular conditions and the activation in the medial prefrontal cortex that was reduced by religious and formalised secular speech conditions but increased during improvised secular speech; similarly, frontal regions were deactivated when comparing prayers to their secular equivalents. Discussion These results seem to depict two important factors related with praying in Sahaja Yoga Meditation merging inner concentration and social cognition. First, the perception of the surroundings mediated by the thalamus may be decreased during these prayers probably due to the establishment of inner concentration and, second, frontal deactivation effects could be related to reduced social judgement and ‘mentalizing’, particularly in the medial prefrontal cortex. Our findings suggest that praying by Sahaja Yoga Meditation practitioners is neurophenomenologically different from the social cognitive attempt of praying within Christian praying practices.

ObjectiveTo study the white matter connections between anterior cingulate cortex, anterior insula and amygdala as key regions of the frontal-limbic network that have been related to meditation.DesignTwenty experienced practitioners of Sahaja Yoga Meditation and twenty nonmeditators matched on age, gender and education level, were scanned using Diffusion Weighted Imaging, using a 3T scanner, and their white matter connectivity was compared using diffusion tensor imaging analyses.ResultsThere were five white matter fiber paths in which meditators showed a larger number of tracts, two of them connecting the same area in both hemispheres: the left and right amygdalae and the left and right anterior insula; and the other three connecting left anterior cingulate with the right anterior insula, the right amygdala and the left amygdala. On the other hand, non-meditators showed larger number of tracts in two paths connecting the left anterior insula with the left amygdala, and the left anterior insula with the left anterior cingulate.ConclusionsThe study shows that long-term practice of Sahaja Yoga Meditation is associated with larger white matter tracts strengthening interhemispheric connections between limbic regions and connections between cingulo-amygdalar and cingulo-insular brain regions related to top-down attentional and emotional processes as well as between top-down control functions that could potentially be related to the witness state perceived through the state of mental silence promoted with this meditation. On the other hand, reduced connectivity strength in left anterior insula in the meditation group could be associated to reduced emotional processing affecting top-down processes.

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.

Transcranial direct current stimulation (tDCS) is a possible alternative to psychostimulants in Attention-Deficit/Hyperactivity Disorder (ADHD), but its mechanisms of action in children and adolescents with ADHD are poorly understood. We conducted the first 15-session, sham-controlled study of anodal tDCS over right inferior frontal cortex (rIFC) combined with cognitive training (CT) in 50 children/adolescents with ADHD. We investigated the mechanisms of action on resting and Go/No-Go Task-based QEEG measures in a subgroup of 23 participants with ADHD (n, sham = 10; anodal tDCS = 13). We failed to find a significant sham versus anodal tDCS group differences in QEEG spectral power during rest and Go/No-Go Task performance, a correlation between QEEG and Go/No-Go Task performance, and changes in clinical and cognitive measures. These findings extend the non-significant clinical and cognitive effects in our sample of 50 children/adolescents with ADHD. Given that the subgroup of 23 participants would have been underpowered, the interpretation of our findings is limited and should be used as a foundation for future investigations. Larger, adequately powered randomized controlled trials should explore different protocols titrated to the individual and using comprehensive measures to assess cognitive, clinical, and neural effects of tDCS and its underlying mechanisms of action in ADHD.

Abstract Background Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. Method We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. Results Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case–control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. Limitations We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. Conclusions Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms.

BackgroundIn mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information.ObjectivesWe describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities.MethodsThe novel approach consists of a modification of Seed-based d Mapping—with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults.DiscussionThe novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools.

Adults with attention-deficit/hyperactivity disorder (ADHD) report increased spontaneous mind wandering (MW) compared to control adults. Since MW is associated with ADHD severity and functional impairment, elucidating the brain mechanisms underlying MW may inform new interventions targeting MW and point to neural markers to monitor their efficacy. Population-based electroencephalographic (EEG) studies suggest that weaker event-related decreases in occipital alpha power characterise periods of MW, but no study has examined event-related brain oscillations during MW in individuals with ADHD. Using an experience-sampling method, we compared adults with ADHD (N = 23) and controls (N = 25) on event-related EEG measures of power modulations and phase consistency during two tasks with high and low demands on working memory and sustained attention, and during periods of MW and task focus. Compared to controls, individuals with ADHD showed weaker alpha power decreases during high working memory demands and across sustained attention demands, weaker theta power increases and phase consistency across working memory demands and during low sustained attention demands, and weaker beta power decreases during low working memory demands. These EEG patterns suggest broadly deficient attentional and motor response processes in ADHD. During MW episodes, adults with ADHD showed weaker alpha power decreases in the sustained attention task and lower theta phase consistency in the working memory task compared to controls. These findings suggest that atypical EEG patterns thought to reflect reduced inhibition of task-irrelevant processes and inconsistent stimulus processing underlie increased MW in adults with ADHD and may be useful for future real-time monitoring of treatment effects.

Changes in brain structure asymmetry have been reported in autism spectrum disorder. Here the authors investigate this issue using a large-scale sample consisting of 54 data sets.

Neuroscience research has shown that meditation practices have effects on brain structure and function. However, few studies have combined information on the effects on structure and function in the same sample. Long-term daily meditation practice produces repeated activity of specific brain networks over years of practice, which may induce lasting structural and functional connectivity (FC) changes within relevant circuits. The aim of our study was therefore to identify differences in FC during the resting state between 23 Sahaja Yoga Meditation experts and 23 healthy participants without meditation experience. Seed-based FC analysis was performed departing from voxels that had shown structural differences between these same participants. The contrast of connectivity maps yielded that meditators showed increased FC between the left ventrolateral prefrontal cortex and the right dorsolateral prefrontal cortex but reduced FC between the left insula and the bilateral mid-cingulate as well as between the right angular gyrus and the bilateral precuneus/cuneus cortices. It thus appears that long-term meditation practice increases direct FC between ventral and dorsal frontal regions within brain networks related to attention and cognitive control and decreases FC between regions of these networks and areas of the default mode network.

We recently reported increased mind wandering (MW) frequency in adults with attention-deficit/hyperactivity disorder (ADHD) relative to controls during high demands on sustained attention, reflecting deficient context regulation of MW. Studies on community samples previously linked context regulation of MW with attenuation in brain sensory processes, reflecting perceptual decoupling, and attentional processes during MW compared to task focus. However, the association between deficient context regulation of MW and these neural processes has not been studied in ADHD. We addressed this question by comparing adults with ADHD (N = 23) and controls (N = 25) on event-related potentials of early sensory processes (P1) and attention allocation (P3) during tasks manipulating cognitive demands (high vs low) on working memory and sustained attention, and during periods of MW and task focus measured through experience-sampling. Compared to controls, adults with ADHD showed reduced P1 during high sustained attention demands, as well as reduced P3 during high working memory demands. These group differences were no longer significant after adding MW frequency as a covariate. Across tasks, adults with ADHD showed no differences from controls on the P1 during MW episodes, but attenuated P1 during task focus. P3 was reduced in adults with ADHD compared to controls during MW, but not during task focus during the sustained attention task. These findings converge to indicate that impairments in early sensory processing in individuals with ADHD seem parallel to increased MW frequency and might reflect inefficient adjustments from periods of MW to task focus.

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.

ObjectivesOur previous study showed that long-term practitioners of Sahaja Yoga Meditation (SYM) had around 7% larger grey matter volume (GMV) in the whole brain compared with healthy controls; however, when testing individual regions, only 5 small brain areas were statistically different between groups. Under the hypothesis that those results were statistically conservative, with the same dataset, we investigated in more detail the regional differences in GMV associated with the practice of SYM, with a different statistical approach.DesignTwenty-three experienced practitioners of SYM and 23 healthy non-meditators matched on age, sex and education level, were scanned using structural magnetic resonance imaging (MRI). Their GMV were extracted and compared using Voxel-Based Morphometry (VBM). Using a novel ad-hoc general linear model, statistical comparisons were made to observe if the GMV differences between meditators and controls were statistically significant.ResultsIn the 16 lobe area subdivisions, GMV was statistically significantly different in 4 out of 16 areas: in right hemispheric temporal and frontal lobes, left frontal lobe and brainstem. In the 116 AAL area subdivisions, GMV difference was statistically significant in 11 areas. The GMV differences were statistically more significant in right hemispheric brain areas.ConclusionsThe study shows that long-term practice of SYM is associated with larger GMV overall, and with significant differences mainly in temporal and frontal areas of the right hemisphere and the brainstem. These neuroplastic changes may reflect emotional and attentional control mechanisms developed with SYM. On the other hand, our statistical ad-hoc method shows that there were more brain areas with statistical significance compared to the traditional methodology which we think is susceptible to conservative Type II errors.

Functional Magnetic Resonance Imaging Neurofeedback (fMRI-NF) targeting brain areas/networks shown to be dysfunctional by previous fMRI research is a promising novel neurotherapy for ADHD. Our pioneering study in 31 adolescents with ADHD showed that fMRI-NF of the right inferior frontal cortex (rIFC) and of the left parahippocampal gyrus (lPHG) was associated with clinical improvements. Previous studies using electro-encephalography-NF have shown, however, that not all ADHD patients learn to self-regulate, and the predictors of fMRI-NF self-regulation learning are not presently known. The aim of the current study was therefore to elucidate the potential predictors of fMRI-NF learning by investigating the relationship between fMRI-NF learning and baseline inhibitory brain function during an fMRI stop task, along with clinical and cognitive measures. fMRI-NF learning capacity was calculated for each participant by correlating the number of completed fMRI-NF runs with brain activation in their respective target regions from each run (rIFC or lPHG); higher correlation values were taken as a marker of better (linear) fMRI-NF learning. Linear correlations were then conducted between baseline measures and the participants’ capacity for fMRI-NF learning. Better fMRI-NF learning was related to increased activation in left inferior fronto-striatal regions during the fMRI stop task. Poorer self-regulation during fMRI-NF training was associated with enhanced activation in posterior temporo-occipital and cerebellar regions. Cognitive and clinical measures were not associated with general fMRI-NF learning across all participants. A categorical analysis showed that 48% of adolescents with ADHD successfully learned fMRI-NF and this was also not associated with any baseline clinical or cognitive measures except that faster processing speed during inhibition and attention tasks predicted learning. Taken together, the findings suggest that imaging data are more predictive of fMRI-NF self-regulation skills in ADHD than behavioural data. Stronger baseline activation in fronto-striatal cognitive control regions predicts better fMRI-NF learning in ADHD.

This review focuses on the evidence for neurotherapeutics for attention deficit/hyperactivity disorder (ADHD). EEG-neurofeedback has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly the dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has been shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share problems with sustained attention, and are proposed to share deficits in switching between default mode and task positive networks. The aim of this study was to investigate shared and disorder-specific brain activation abnormalities during sustained attention in the two disorders. Twenty boys with ADHD, 20 boys with OCD and 20 age-matched healthy controls aged between 12 and 18years completed a functional magnetic resonance imaging (fMRI) version of a parametrically modulated sustained attention task with a progressively increasing sustained attention load. Performance and brain activation were compared between groups. Only ADHD patients were impaired in performance. Group by sustained attention load interaction effects showed that OCD patients had disorder-specific middle anterior cingulate underactivation relative to controls and ADHD patients, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus (IFG). ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network relative to controls, but had disorder-specific overactivation in anterior default mode regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. In sum, ADHD and OCD patients showed mostly disorder-specific patterns of brain abnormalities in both task positive salience/ventral attention networks with lateral frontal deficits in ADHD and middle ACC deficits in OCD, as well as in their deactivation patterns in medial frontal DMN regions. The findings suggest that attention performance in the two disorders is underpinned by disorder-specific activation patterns. Keywords: ADHD, DMN, fMRI, OCD, Vigilance

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide 12 easy-to-implement consensus recommendations and point out the problems that can arise when they are not followed. Furthermore, we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.

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.

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment.

Childhood maltreatment is associated with error hypersensitivity. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA) interaction on functional brain connectivity during error processing in medication/drug-free adolescents. Functional connectivity was compared, using generalized psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 22 age- and gender-matched medication-naïve and substance abuse-free adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed an individually adjusted tracking stop-signal task, designed to elicit 50% inhibition failures. During inhibition failures, abused participants relative to healthy controls exhibited reduced connectivity between right and left putamen, bilateral caudate and anterior cingulate cortex (ACC), and between right supplementary motor area (SMA) and right inferior and dorsolateral prefrontal cortex. Abuse-related connectivity abnormalities were associated with longer abuse duration. No group differences in connectivity were observed for successful inhibition. The findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-cingulo-striatal networks during error processing. Furthermore that the severity of connectivity abnormalities increases with abuse duration. Reduced connectivity of error detection networks in maltreated individuals may be linked to constant monitoring of errors in order to avoid mistakes which, in abusive contexts, are often associated with harsh punishment.

Childhood maltreatment is associated with attention deficits. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA, FKBP5) interaction on functional brain connectivity during sustained attention in medication/drug-free adolescents. Functional connectivity was compared, using generalised psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 21 age-and gender-matched adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed a parametrically modulated vigilance task requiring target detection with a progressively increasing load of sustained attention. Behaviourally, participants exposed to childhood abuse had increased omission errors compared to healthy controls. During the most challenging attention condition abused participants relative to controls exhibited reduced connectivity, with a left-hemispheric bias, in typical fronto-parietal attention networks, including dorsolateral, rostromedial and inferior prefrontal and inferior parietal regions. Abuse-related connectivity abnormalities were exacerbated in individuals homozygous for the risky C-allele of the single nucleotide polymorphism rs3800373 of the FK506 Binding Protein 5 (FKBP5) gene. Findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-parietal attention networks and that the FKBP5 genotype moderates neurobiological vulnerability to abuse. These findings represent a first step towards the delineation of abuse-related neurofunctional connectivity abnormalities, which hopefully will facilitate the development of specific treatment strategies for victims of childhood maltreatment.

Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse.

OBJECTIVES:To investigate regional differences in grey matter volume associated with the practice of Sahaja Yoga Meditation. DESIGN:Twenty three experienced practitioners of Sahaja Yoga Meditation and twenty three non-meditators matched on age, gender and education level, were scanned using structural Magnetic Resonance Imaging and their grey matter volume were compared using Voxel-Based Morphometry. RESULTS:Grey matter volume was larger in meditators relative to non-meditators across the whole brain. In addition, grey matter volume was larger in several predominantly right hemispheric regions: in insula, ventromedial orbitofrontal cortex, inferior temporal and parietal cortices as well as in left ventrolateral prefrontal cortex and left insula. No areas with larger grey matter volume were found in non-meditators relative to meditators. CONCLUSIONS:The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger grey matter volume overall, and with regional enlargement in several right hemispheric cortical and subcortical brain regions that are associated with sustained attention, self-control, compassion and interoceptive perception. The increased grey matter volume in these attention and self-control mediating regions suggests use-dependent enlargement with regular practice of this meditation.

BACKGROUND:Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC). METHODS:In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms. OUTCOMES:The primary outcome measure was 'core AN symptoms', a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed. RESULTS:Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well-tolerated and was considered an acceptable intervention. CONCLUSIONS:This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy. TRIAL REGISTRATION:www.Controlled-Trials.com ISRCTN22851337.

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, but diagnosed by subjective clinical and rating measures. The study's aim was to apply Gaussian process classification (GPC) to grey matter (GM) volumetric data, to assess whether individual ADHD adolescents can be accurately differentiated from healthy controls based on objective, brain structure measures and whether this is disorder-specific relative to autism spectrum disorder (ASD).Twenty-nine adolescent ADHD boys and 29 age-matched healthy and 19 boys with ASD were scanned. GPC was applied to make disorder-specific predictions of ADHD diagnostic status based on individual brain structure patterns. In addition, voxel-based morphometry (VBM) analysis tested for traditional univariate group level differences in GM.The pattern of GM correctly classified 75.9% of patients and 82.8% of controls, achieving an overall classification accuracy of 79.3%. Furthermore, classification was disorder-specific relative to ASD. The discriminating GM patterns showed higher classification weights for ADHD in earlier developing ventrolateral/premotor fronto-temporo-limbic and stronger classification weights for healthy controls in later developing dorsolateral fronto-striato-parieto-cerebellar networks. Several regions were also decreased in GM in ADHD relative to healthy controls in the univariate VBM analysis, suggesting they are GM deficit areas.The study provides evidence that pattern recognition analysis can provide significant individual diagnostic classification of ADHD patients and healthy controls based on distributed GM patterns with 79.3% accuracy and that this is disorder-specific relative to ASD. Findings are a promising first step towards finding an objective differential diagnostic tool based on brain imaging measures to aid with the subjective clinical diagnosis of ADHD.