The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis.

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34-0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36-0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.

The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS).

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 .

Enhanced amygdala-anterior cingulate white matter structural connectivity in Sahaja Yoga Meditators.

OBJECTIVE: To 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. DESIGN: Twenty 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. RESULTS: There 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. CONCLUSIONS: The 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.

Attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD; also known as hyperkinetic disorder) is a common neurodevelopmental condition that affects children and adults worldwide. ADHD has a predominantly genetic aetiology that involves common and rare genetic variants. Some environmental correlates of the disorder have been discovered but causation has been difficult to establish. The heterogeneity of the condition is evident in the diverse presentation of symptoms and levels of impairment, the numerous co-occurring mental and physical conditions, the various domains of neurocognitive impairment, and extensive minor structural and functional brain differences. The diagnosis of ADHD is reliable and valid when evaluated with standard diagnostic criteria. Curative treatments for ADHD do not exist but evidence-based treatments substantially reduce symptoms and/or functional impairment. Medications are effective for core symptoms and are usually well tolerated. Some non-pharmacological treatments are valuable, especially for improving adaptive functioning. Clinical and neurobiological research is ongoing and could lead to the creation of personalized diagnostic and therapeutic approaches for this disorder.

Mind and skin: Exploring the links between inflammation, sleep disturbance and neurocognitive function in patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronic, pruritic and inflammatory, dry skin condition with many known comorbidities. These include airway disease, food allergies, atopic eye disease and autoimmune conditions. Furthermore, there is often significant sleep disturbance as well as increased psychological distress and mental health problems. Severe AD therefore often has a significant impact on the quality of life of both patients and their families. In this review we discuss recent findings on the putative links between AD, its association with itch, sleep disturbance and neuropsychiatric morbidity, including the role of inflammation in these conditions. Itch was thought to predominantly drive sleep disruption in AD. We now understand changes in sleep influence immune cell distribution and the associated inflammatory cytokines, which suggests a bidirectional relationship between AD and sleep. We also increasingly recognize inflammation as a key driver in psychological symptoms and disorders. The link between cutaneous, systemic and possible brain inflammation could at least in part be driven by the sleep deprivation and itch-driven neuronal proliferation seen in AD.

Monitoring the neural activity associated with praying in Sahaja Yoga meditation.

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.

Clinical and cognitive effects of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders: a systematic review and meta-analysis.

This pre-registered (CRD42022322038) systematic review and meta-analysis investigated clinical and cognitive outcomes of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders. PubMed, OVID, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and VIP database for Chinese technical periodicals were searched (until 16/03/2022) to identify trials investigating cognitive and clinical outcomes of eTNS in neurological or psychiatric disorders. The Cochrane Risk of Bias 2.0 tool assessed randomized controlled trials (RCTs), while the Risk of Bias of Non-Randomized Studies (ROBINS-I) assessed single-arm trials. Fifty-five peer-reviewed articles based on 48 (27 RCTs; 21 single-arm) trials were included, of which 12 trials were meta-analyzed (N participants = 1048; of which ~3% ADHD, ~3% Epilepsy, ~94% Migraine; age range: 10-49 years). The meta-analyses showed that migraine pain intensity (K trials = 4, N = 485; SMD = 1.03, 95% CI[0.84-1.23]) and quality of life (K = 2, N = 304; SMD = 1.88, 95% CI[1.22-2.53]) significantly improved with eTNS combined with anti-migraine medication. Dimensional measures of depression improved with eTNS across 3 different disorders (K = 3, N = 111; SMD = 0.45, 95% CI[0.01-0.88]). eTNS was well-tolerated, with a good adverse event profile across disorders. eTNS is potentially clinically relevant in other disorders, but well-blinded, adequately powered RCTs must replicate findings and support optimal dosage guidance.

White matter alterations in Attention-Deficit/Hyperactivity Disorder (ADHD): a systematic review of 129 diffusion imaging studies with meta-analysis.

Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed, Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age, sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23 datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to consistency and comparability among studies, and should be addressed in future investigations.

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.

Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes.

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be "probably blinded" (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[-0.01 to -0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[-0.03 to-0.28]). These findings remained when analyses were restricted to trials (n: 5-13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02-0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04-0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09-0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24-0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31-0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5-15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5-7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms.

Transcranial direct current stimulation (tDCS) combined with cognitive training in adolescent boys with ADHD: a double-blind, randomised, sham-controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) could be a side-effect-free alternative to psychostimulants in attention-deficit/hyperactivity disorder (ADHD). Although there is limited evidence for clinical and cognitive effects, most studies were small, single-session and stimulated left dorsolateral prefrontal cortex (dlPFC). No sham-controlled study has stimulated the right inferior frontal cortex (rIFC), which is the most consistently under-functioning region in ADHD, with multiple anodal-tDCS sessions combined with cognitive training (CT) to enhance effects. Thus, we investigated the clinical and cognitive effects of multi-session anodal-tDCS over rIFC combined with CT in double-blind, randomised, sham-controlled trial (RCT, ISRCTN48265228). METHODS: Fifty boys with ADHD (10-18 years) received 15 weekday sessions of anodal- or sham-tDCS over rIFC combined with CT (20 min, 1 mA). ANCOVA, adjusting for baseline measures, age and medication status, tested group differences in clinical and ADHD-relevant executive functions at posttreatment and after 6 months. RESULTS: ADHD-Rating Scale, Conners ADHD Index and adverse effects were significantly lower at post-treatment after sham relative to anodal tDCS. No other effects were significant. CONCLUSIONS: This rigorous and largest RCT of tDCS in adolescent boys with ADHD found no evidence of improved ADHD symptoms or cognitive performance following multi-session anodal tDCS over rIFC combined with CT. These findings extend limited meta-analytic evidence of cognitive and clinical effects in ADHD after 1-5 tDCS sessions over mainly left dlPFC. Given that tDCS is commercially and clinically available, the findings are important as they suggest that rIFC stimulation may not be indicated as a neurotherapy for cognitive or clinical remediation for ADHD.

Double-Blind, Sham-Controlled Randomized Trial Testing the Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD.

OBJECTIVE: Functional MRI neurofeedback (fMRI-NF) could potentially be a novel, safe nonpharmacological treatment for attention deficit hyperactivity disorder (ADHD). A proof-of-concept randomized controlled trial of fMRI-NF of the right inferior frontal cortex (rIFC), compared to an active control condition, showed promising improvement of ADHD symptoms (albeit in both groups) and in brain function. However, comparison with a placebo condition in a larger trial is required to test efficacy. METHODS: This double-blind, sham-controlled randomized controlled trial tested the effectiveness and efficacy of fMRI-NF of the rIFC on symptoms and executive functions in 88 boys with ADHD (44 each in the active and sham arms). To investigate treatment-related changes, groups were compared at the posttreatment and 6-month follow-up assessments, controlling for baseline scores, age, and medication status. The primary outcome measure was posttreatment score on the ADHD Rating Scale (ADHD-RS). RESULTS: No significant group differences were found on the ADHD-RS. Both groups showed similar decreases in other clinical and cognitive measures, except for a significantly greater decrease in irritability and improvement in motor inhibition in sham relative to active fMRI-NF at the posttreatment assessment, covarying for baseline. There were no significant side effects or adverse events. The active relative to the sham fMRI-NF group showed enhanced activation in rIFC and other frontal and temporo-occipital-cerebellar self-regulation areas. However, there was no progressive rIFC upregulation, correlation with ADHD-RS scores, or transfer of learning. CONCLUSIONS: Contrary to the hypothesis, the study findings do not suggest that fMRI-NF of the rIFC is effective in improving clinical symptoms or cognition in boys with ADHD.

Transcranial Direct Current Stimulation vs Sham for the Treatment of Inattention in Adults With Attention-Deficit/Hyperactivity Disorder: The TUNED Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) may improve symptoms of inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, previous trials are characterized by small sample sizes, heterogeneous methodologies, and short treatment periods using clinic-based tDCS. Objective: To determine the efficacy and safety of home-based tDCS in treating inattention symptoms in adult patients with ADHD. Design, Setting, and Participants: Randomized, double-blind, parallel, sham-controlled clinical trial (tDCS for the Treatment of Inattention Symptoms in Adult Patients With ADHD [TUNED]), conducted from July 2019 through July 2021 in a single-center outpatient academic setting. Of 277 potential participants screened by phone, 150 were assessed for eligibility on site, and 64 were included. Participants were adults with ADHD, inattentive or combined subtype. Exclusion criteria included current stimulant drug treatment, current moderate to severe symptoms of depression or anxiety, diagnosis of bipolar disorder with a manic or depressive episode in the last year, diagnosis of schizophrenia or another psychotic disorder, and diagnosis of autism spectrum disorder; 55 of participants completed follow-up after 4 weeks. Interventions: Thirty-minute daily sessions of home-based tDCS for 4 weeks, 2 mA anodal-right and cathodal-left prefrontal stimulation with 35-cm2 carbon electrodes. Main Outcomes and Measures: Inattentive scores in the clinician-administered version of the Adult ADHD Self-report Scale version 1.1 (CASRS-I). Results: Included in this trial were 64 participants with ADHD (31 [48%] inattentive presentation and 33 [52%] combined presentation), with a mean (SD) age of 38.3 (9.6) years. Thirty participants (47%) were women and 34 (53%) were men. Fifty-five finished the trial. At week 4, the mean (SD) inattention score, as measured with CASRS-I, was 18.88 (5.79) in the active tDCS group and 23.63 (3.97) in the sham tDCS group. Linear mixed-effects models revealed a statistically significant treatment by time interaction for CASRS-I (ßinteraction = -3.18; 95% CI, -4.60 to -1.75; P < .001), showing decreased symptoms of inattention in the active tDCS group over the 3 assessments compared to the sham tDCS group. Mild adverse events were more frequent in the active tDCS group, particularly skin redness, headache, and scalp burn. Conclusions and Relevance: In this randomized clinical trial, daily treatment with a home-based tDCS device over 4 weeks improved attention in adult patients with ADHD who were not taking stimulant medication. Home-based tDCS could be a nonpharmacological alternative for patients with ADHD. Trial Registration: ClinicalTrials.gov Identifier: NCT04003740.

Event-related brain dynamics during mind wandering in attention-deficit/hyperactivity disorder: An experience-sampling approach.

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.

The effect of transcranial direct current stimulation (tDCS) combined with cognitive training on EEG spectral power in adolescent boys with ADHD: A double-blind, randomized, sham-controlled trial.

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.

Neurotherapeutics for ADHD: Do they work?

This paper reflects on the use of neurotherapeutics for attention-deficit/hyperactivity disorder (ADHD). ADHD is the most imaged child psychiatric disorder, with over 3 decades of magnetic resonance imaging (MRI) research. Findings are relatively homogeneous compared to other psychiatric conditions with consistent evidence for differences, albeit small, relative to healthy controls in the structure and function of several frontal, parietotemporal, and striatal brain regions as well as their inter-regional structural and functional connections. The functional deficits have been targeted with modern neurotherapeutics, including neurofeedback (using most commonly electroencephalography and more recently functional near-infrared spectroscopy and functional MRI) and non-invasive brain stimulation (such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation, or external trigeminal nerve stimulation). Except for electroencephalography-neurofeedback, the majority of neurotherapeutic studies have been relatively small, with very heterogenous research protocols and outcome measures and-likely as a consequence-inconsistent findings. Furthermore, most brain stimulation studies have tested effects on cognitive functions rather than clinical symptoms. So far, findings have not been very promising. Future studies require systematic testing of optimal protocols in large samples or homogenous subgroups to understand response prediction that could lead to individualized treatment.

Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium.

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.