Objective: Trigeminal nerve stimulation (TNS), a minimal risk, non-invasive neuromodulation method, has showed potential benefits for attention-deficit/hyperactivity disorder (ADHD) in an unblinded open study. This blinded sham-controlled trial was conducted to assess efficacy and safety of TNS for ADHD, as well as potential changes in brain spectral power using resting-state quantitative electroencephalography (qEEG). Method: 62 children aged 8-12 years, with full-scale IQ ≥ 85 and KSADS-diagnosed ADHD, were randomized to four weeks nightly treatment with active or sham TNS, followed by one-week without intervention. Assessments included weekly clinician-administered ADHD-Rating Scales (ADHD-RS) and Clinical Global Impression (CGI) scales, and qEEG at baseline and week 4. Results: ADHD-RS totals showed significant group-by-time interactions (F = 8.12, df = 1/228, p = .005); week 4 Cohen's d = .5. CGI-Improvement also favored active treatment (Chisq = 8.75, df = 1/168, p = .003); number-needed-to-treat (NNT) = 3. Resting-state qEEG showed increased spectral power in right frontal and frontal midline frequency bands with active TNS. Neither group had clinically meaningful adverse events. Conclusion: This study demonstrates TNS efficacy for ADHD in a blinded sham-controlled trial, with estimated treatment effect size similar to non-stimulants. TNS is well-tolerated and

Background: A growing body of research has identified abnormal visual information processing in attention-deficit hyperactivity disorder (ADHD). In particular, slow processing speed and increased reliance on visuo-perceptual strategies have become evident.Objective: The current study used recently developed fMRI methods to replicate and further examine abnormal rightward biased visual information processing in ADHD and to further characterize the nature of this effect; we tested its association with several large-scale distributed network systems.Method: We examined fMRI BOLD response during letter and location judgment tasks, and directly assessed visual network asymmetry and its association with large-scale networks using both a voxelwise and an averaged signal approach.Results: Initial within-group analyses revealed a pattern of left-lateralized visual cortical activity in controls but right-lateralized visual cortical activity in ADHD children. Direct analyses of visual network asymmetry confirmed atypical rightward bias in ADHD children compared to controls. This ADHD characteristic was atypically associated with reduced activation across several extra-visual networks, including the default mode network (DMN). We also found atypical associations between DMN activation and ADHD subjects’ inattentive symptoms and task performance.Conclusion: The current study demonstrated rightward VNA in ADHD during a simple letter discrimination task. This result adds an important novel consideration to the growing literature identifying abnormal visual processing in ADHD. We postulate that this characteristic reflects greater perceptual engagement of task-extraneous content, and that it may be a basic feature of less efficient top-down task-directed control over visual processing. We additionally argue that abnormal DMN function may contribute to this characteristic.

Background: Abundant work indicates ADHD abnormal posterior brain structure and function, including abnormal structural and functional asymmetries and reduced corpus callosum size. However, this literature has attracted considerably less research interest than fronto-striatal findings.Objective: To help address this imbalance, the current study replicates and extends our previous work showing abnormal parietal brain function in ADHD adults during the Conner’s Continuous Performance Test (CPT).Method: Our previous study found that ADHD adults had increased rightward EEG beta (16–21 Hz) asymmetry in inferior parietal brain regions during the CPT (p = 0.00001), and that this metric exhibited a lack of normal correlation (i.e., observed in controls) with beta asymmetry at temporal–parietal regions. We re-tested these effects in a new ADHD sample and with both new and old samples combined. We additionally examined: (a) EEG asymmetry in multiple frequency bands, (b) unilateral effects for all asymmetry findings, and (c) the association between EEG asymmetry and a battery of cognitive tests.Results: We replicated our original findings by demonstrating abnormal rightward inferior parietal beta asymmetry in adults with ADHD during the CPT, and again this metric exhibited abnormal reduced correlation to temporal–parietal beta asymmetry. Novel analyses also demonstrated a broader pattern of rightward beta and theta asymmetry across inferior, superior, and temporal–parietal brain regions, and showed that rightward parietal asymmetry in ADHD was atypically associated with multiple cognitive tests.Conclusion: Abnormal increased rightward parietal EEG beta asymmetry is an important feature of ADHD. We speculate that this phenotype may occur with any form of impaired capacity for top-down task-directed control over sensory encoding functions, and that it may reflect associated increase of attentional shifting and compensatory sustained/selective attention.

Objective The pathophysiology of Chronic Tic Disorders (CTDs), including Tourette Syndrome, remains poorly understood. The goal of this study was to compare neural activity and connectivity during a voluntary movement (VM) paradigm that involved cued eye blinks among children with and without CTDs. Using the precise temporal resolution of electroencephalography (EEG), we used the timing and location of cortical source resolved spectral power activation and connectivity to map component processes such as visual attention, cue detection, blink regulation and response monitoring. We hypothesized that neural activation and connectivity during the cued eye blink paradigm would be significantly different in regions typically associated with effortful control of eye blinks, such as frontal, premotor, parietal, and occipital cortices between children with and without CTD. Method Participants were 40 children (23 with CTD, 17 age-matched Healthy Control [HC]), between the ages of 8–12 (mean age = 9.5) years old. All participants underwent phenotypic assessment including diagnostic interviews, behavior rating scales and 128-channel EEG recording. Upon presentation of a cue every 3 s, children were instructed to make an exaggerated blink. Results Behaviorally, the groups did not differ in blink number, latency, or ERP amplitude. Within source resolved clusters located in left dorsolateral prefrontal cortex, posterior cingulate, and supplemental motor area, children with CTD exhibited higher gamma band spectral power relative to controls. In addition, significant diagnostic group differences in theta, alpha, and beta band power in inferior parietal cortex emerged. Spectral power differences were significantly associated with clinical characteristics such as tic severity and premonitory urge strength. After calculating dipole density for 76 anatomical regions, the CTD and HC groups had 70% overlap of top regions with the highest dipole density, suggesting that similar cortical networks were used across groups to carry out the VM. The CTD group exhibited significant information flow increase and dysregulation relative to the HC group, particularly from occipital to frontal regions. Conclusion Children with CTD exhibit abnormally high levels of neural activation and dysregulated connectivity among networks used for regulation and effortful control of voluntary eye blinks.

Glucocorticoids serve as important therapeutic agents in diseases of inflammation, but clinical use, especially in advanced septic shock, remains controversial because of the unpredictable response. Prior studies correlate human glucocorticoid receptor (hGR) isoforms with a decreased response to steroid therapy. Further analysis of additional hGR isoforms may improve the understanding of the steroid response. Ninety-seven human volunteers' blood samples were surveyed for hGR isoforms. An isoform matching National Center for Biotechnology Informatics (NCBI) hGRα (hGR NCBI) served as a reference. Two isoforms were of particular interest-one isoform had three nonsynonymous single-nucleotide polymorphisms (SNPs) (hGR NS-1), and the second had a single-nucleotide deletion (hGR DL-1) resulting in a truncated protein. Transactivation potentials were measured using a luciferase reporter assay. Human glucocorticoid receptor NS-1 had activity more than twice of hGR NCBI, whereas hGR DL-1 demonstrated less than 10% of the activity of hGR NCBI. Cotransfection of two isoforms revealed that the presence of hGR NS-1 increased transactivation potential, whereas hGR DL-1 decreased activity. Synthetic constructs isolating individual and paired SNPs of hGR NS-1 were created to identify the SNP responsible for hyperactivity. Transactivation studies revealed a SNP within the ligand-binding domain exerted the greatest influence over hyperactivity. In evaluating the response to hydrocortisone, hGR NCBI and hGR NS-1 displayed an increased dose-dependent response, but hGR NS-1 had a response more than twice hGR NCBI. Characterization of the novel hyperactive hGR NS-1 provides insight into a possible mechanism underlying the unpredictable response to steroid treatment.