Scaffolding the attention-deficit/hyperactivity disorder brain using transcranial direct current and random noise stimulation: A randomized controlled trial.

OBJECTIVE: Improving symptomology and cognitive deficits in neurodevelopmental disorders is a crucial challenge. We examined whether neurostimulation protocols, which have been shown to yield long-term effects when combined with cognitive training, could benefit children with Attention-deficit/hyperactivity-disorder (ADHD), the most common neurodevelopmental disorder in childhood. METHODS: We used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD, who received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or random noise stimulation (tRNS) over the bilateral dlPFC, while completing executive functions training. RESULTS: For our primary outcome, tRNS yielded a clinical improvement as indicated by the reduced ADHD rating-scale score from baseline, and in comparison to the changes observed in tDCS. The effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, tRNS improved working memory compared to tDCS, and a larger tRNS effect on ADHD rating-scale was predicted for those who showed the greatest improvement in working memory. CONCLUSIONS: We found that our intervention can have a lasting effect, rather than a merely immediate effect as was shown for in previous medical interventions in ADHD. SIGNIFICANCE: Our results provide a promising direction toward a novel intervention in ADHD.

Homozygous mutation in MFSD2A, encoding a lysolipid transporter for docosahexanoic acid, is associated with microcephaly and hypomyelination.

The major facilitator superfamily domain-containing protein 2A (MFSD2A) is a constituent of the blood-brain barrier and functions to transport lysophosphatidylcholines (LPCs) into the central nervous system. LPCs such as that derived from docosahexanoic acid (DHA) are indispensable to neurogenesis and maintenance of neurons, yet cannot be synthesized within the brain and are dependent on MFSD2A for brain uptake. Recent studies have implicated MFSD2A mutations in lethal and non-lethal microcephaly syndromes, with the severity correlating to the residual activity of the transporter. We describe two siblings with shared parental ancestry, in whom we identified a homozygous missense mutation (c.1205C > A; p.Pro402His) in MFSD2A. Both affected individuals had microcephaly, hypotonia, appendicular spasticity, dystonia, strabismus, and global developmental delay. Neuroimaging revealed paucity of white matter with enlarged lateral ventricles. Plasma lysophosphatidylcholine (LPC) levels were elevated, reflecting reduced brain transport. Cell-based studies of the p.Pro402His mutant protein indicated complete loss of activity of the transporter despite the non-lethal, attenuated phenotype. The aggregate data of MFSD2A-associated genotypes and phenotypes suggest that additional factors, such as nutritional supplementation or modifying genetic factors, may modulate the severity of disease and call for consideration of treatment options for affected individuals.

The effect of environmental distractors incorporation into a CPT on sustained attention and ADHD diagnosis among adolescents.

BACKGROUND: Diagnosis of ADHD in adolescents involves specific challenges. Conventional CPT's may fail to consistently distinguish ADHD from non-ADHD due to insufficient cognitive demands. The aim of this study was to explore whether the incorporation of environmental distractors into a CPT would increase its ability to distinguish ADHD from non-ADHD adolescents. NEW METHOD: Using the rate of omission errors as a measure of difficulty in sustained attention, this study examined whether ADHD adolescents are more distracted than controls and which type of distractors is more effective in terms of ADHD diagnosis. The study employed the MOXO-CPT version which includes visual and auditory stimuli serving as distractors. Participants were 176 adolescents aged 13-18 years, 133 diagnosed with ADHD and 43 without ADHD. RESULTS AND COMPARISON WITH EXISTING METHODS: Results showed that ADHD adolescents produced significantly more omission errors in the presence of pure visual distractors and the combination of visual and auditory distractors than in no-distractors conditions. Distracting stimuli had no effect on CPT performance of non-ADHD adolescents. ROC analysis further demonstrated that the mere presence of distractors improved the utility of the test. CONCLUSIONS: This study provides evidence that incorporation of environmental distractors into a CPT is useful in term of ADHD diagnosis. ADHD adolescents were more distracted than controls by all types of environmental distractors. ADHD adolescents were more distracted by pure visual distractors and by the combination of distractors than by pure auditory ones.

A virtual reality system combined with biofeedback for treating pediatric chronic headache--a pilot study.

OBJECTIVE: Pediatric headache is highly widespread and is associated with distress and reduced quality of life. Pharmacological treatment of chronic headache in children has been only partially effective and, as in medication-overuse headache, can sometimes be counterproductive. Therefore, there is a substantial need to develop other effective methods of treatment. Here we present the rationale, feasibility, and preliminary results of a pilot study applying a novel system, combining virtual reality and biofeedback, aimed as an abortive treatment of pediatric chronic headache. DESIGN: A prospective single-arm open-label, pilot study. Ten children attending an outpatient pediatric neurology clinic were treated by the proposed system. Participants practiced relaxation with biofeedback and learned to associate successful relaxation with positive pain-free virtual images of themselves. RESULTS: Nine patients completed the 10-session intervention. Ratings of pain, daily functioning, and quality of life improved significantly at 1 and at 3 months posttreatment. Most patients reported applying their newly acquired relaxation and imagery skills to relieve headache outside the lab. CONCLUSION: This novel system, combining biofeedback and virtual reality, is feasible for pediatric use. Randomized controlled studies in larger populations are needed in order to determine the utility of the system in reducing headache, improving daily functioning, and elevating quality of life.