Context Regulation of Mind Wandering in ADHD

OBJECTIVE: We aimed to understand the association between MW frequency and clinical measures, context regulation of MW and group differences in task performance. METHOD: 27 adults with ADHD and 29 controls performed tasks manipulating demand on working memory and sustained attention, and recorded their MW frequency using probes. RESULTS: A significant association between MW frequency and the clinical measures was demonstrated. Along with increased MW frequency, individuals with ADHD reported decreasing MW frequency during increasing demands on working memory (context regulation), but not on sustained attention (deficient context regulation). Controls, however, maintained continuous task focus across all conditions. Group differences in task performance were no longer significant after adding MW frequency as a covariate. CONCLUSION: Deficient context regulation during increasing demands on sustained attention suggests that sustained attention deficits may play a more important role in regulation of MW in ADHD. MW frequency might also underpin performance deficits in ADHD

Cell lineage-specific mitochondrial resilience during mammalian organogenesis

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments

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

An in vitro toxicological assessment of two electronic cigarettes: E-liquid to aerosolisation

Interest in the toxicological assessment of iterations of e-cigarette devices, e-liquid formulations and flavour use is increasing. Here, we describe a multiple test matrix and in vitro approach to assess the biological impact of differing e-cigarette activation mechanism (button vs. puff-activated) and heating technology (cotton vs. ceramic wick). The e-liquids selected for each device contained the same nicotine concentration and flavourings. We tested both e-liquid and aqueous extract of e-liquid aerosol using a high throughput cytotoxicity and genotoxicity screen. We also conducted whole aerosol assessment both in a reconstituted human airway lung tissue (MucilAir) with associated endpoint assessment (cytotoxicity, TEER, cilia beat frequency and active area) and an Ames whole aerosol assay with up to 900 consecutive undiluted puffs. Following this testing it is shown that the biological impact of these devices is similar, taking into consideration the limitations and capturing efficiencies of the different testing matrices. We have contextualised these responses against previous published reference cigarette data to establish the comparative reduction in response consistent with reduced risk potential of the e-cigarette products tested in this study as compared to conventional cigarettes

The effect of transcranial direct current stimulation (tDCS) combined with cognitive training on EEG spectral power in adolescent boys with ADHD

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