Faculty Bibliography

Increased reaction time variability (RTV) is one of the most replicable behavioral correlates of attention-deficit/hyperactivity disorder (ADHD). However, this may not be specific to ADHD but a more general marker of psychopathology. Here we compare RT variability in individuals with ADHD and those with other childhood internalizing and externalizing conditions both in terms of standard (i.e., the standard deviation of reaction time) and alternative indices that capture low-frequency oscillatory patterns in RT variations over time thought to mark periodic lapses of attention in ADHD. A total of 667 participants (6-12 years old) were classified into non-overlapping diagnostic groups consisting of children with fear disorders (n = 91), distress disorders (n = 56), ADHD (n = 103), oppositional defiant or conduct disorder (ODD/CD; n = 40) and typically developing controls (TDC; n = 377). We used a simple two-choice reaction time task to measure reaction time. The strength of oscillations in RTs across the session was extracted using spectral analyses. Higher RTV was present in ADHD compared to all other disorder groups, effects that were equally strong across all frequency bands. Interestingly, we found that lower RTV to characterize ODD/CD relative to TDC, a finding that was more pronounced at lower frequencies. In general, our data support RTV as a specific marker of ADHD. RT variation across time in ADHD did not show periodicity in a specific frequency band, not supporting that ADHD RTV is the product of spontaneous periodic lapses of attention. Low-frequency oscillations may be particularly useful to differentiate ODD/CD from TDC.

A growing body of research suggests that symptoms of autism spectrum disorder (ASD) may present differently in males and females. This study examined gender differences in ASD symptoms and developmental functioning, using the Baby and Infant Screen for Children with aUtism Traits, Part 1 (BISCUIT-Part 1) and the Battelle Developmental Inventory, 2nd Edition (BDI-2), amongst children aged 17-37 months meeting ASD diagnostic criteria (n = 1317). No gender differences were found in regards to overall symptom severity or symptom domains on the BISCUIT-Part 1 when gender groups were matched by cognitive ability. Females with ASD had greater motor deficits and less communication impairment compared to their male counterparts as measured by the BDI-2. Secondary analyses examining item endorsement patterns were also conducted. Implications of the findings are discussed.

Introduction: Prior studies have shown beneficial effects of repetitive Transcranial Magnetic Stimulation (rTMS) on motor symptoms of Parkinson's disease (PD) [1]. In animal models, rTMS has also shown to enhance Brain-derived neurotrophic factor-Tropomyosin receptor kinase B (BDNF-TrkB) signaling by increasing the affinity of BDNF for its receptor [2]. Aerobic exercise (AEx) has demonstrated to improve motor symptoms of Parkinson's disease (PD) and BDNF-TrkB signaling has been proposed as a relevant contributing mechanism [3]. Objective(s): 1- To explore differences in BDNF-TrkB signaling between PD and healthy controls (HC). 2- To explore plasticity biomarkers and motor symptoms effects of AEx combined with repetitive TMS (rTMS) in PD (real Vs. sham). Method(s): First, we conducted a cross-sectional comparison of BDNF-TrkB signaling between HC and PD patients. Secondly, PD participants were assigned to a double-blind randomized study of AEx paired with rTMS or sham. AEx included 10 daily 40-minute sessions on a recumbent linear cross trainer. Immediately before each AEx session, PD participants receive a total of 3600 pulses of 5 Hz rTMS (real or sham) over primary motor cortex (left, right hands and lower limbs mid-line). Study outcomes were obtained at baseline, 1-day post-intervention (FU1) and 1-month post-intervention (FU2). BDNF-TrkB signaling was obtained from peripheral blood lymphocytes extracted between 9:00 to 10:00 am. Neurophysiological parameters were cortical silent period (cSP), motor threshold (MT) and paired-associative stimulation-25. Motor outcomes were measured with the Unified Parkinson's Disease Rating Scale (UPDRS) and Timed Up-and-Go (TUG) test. Result(s): Twenty one participants (16 PD and 5 HC) completed all study visits. All procedures were well tolerated. In the cross-sectional phase, analysis revealed that BDNF-TrkB signaling was 46.2% lower in PD compared to HC (p<0.01). In the prospective randomized phase, BDNF-TrkB signaling increased significantly compared to baseline in both study groups (FU1: real 43.3%, sham: 35.5%; FU2 real 30.8%, Sham 28.7%); however, there was no difference between groups. At FU2, cSP was significantly prolonged among PD participants receiving real rTMS vs sham (P=0.047). Secondary analysis per group showed that UPDRS III and TUG significantly improved at FU2 only in participants receiving real rTMS. Conclusion(s): Study showed that BDNF-TrkB signaling was clearly deficient in PD participants and partially restored after 2-week AEx (with/without rTMS). Prolongation of cSP in participant's receiving real rTMS could reflect more adequate restorative modulation. The addition of rTMS to AEx might improve motor benefits however does not provide additive effects over BDNF-TrkB signaling. Sponsor: Ofer Nemirovsky.

Introduction: Fatigue is one of the most prevalent and largely under-assessed non-motor symptoms in PD. Current potential therapies have limited effectiveness. Presently, tDCS has shown potential to improve certain symptoms of PD. We designed an RS-tDCS protocol to allow study participation from a patient's home while maintaining clinical trial standards. We utilized a live video-conferencing platform and specially designed equipment that 'unlocks' one session at a time.Study objective: to assess feasibility and explore the therapeutic potential of remotely supervised tDCS (RS-tDCS) paired with cognitive training (CT) for Parkinson's disease (PD) related fatigue: preliminary results. Method(s): Preliminary analysis of eighteen PD patients, age 35-89 that participated in a double-blind, randomized, sham controlled study with RS-tDCS paired with CT. Each participant completed 10 tDCS sessions (20-minute, 2.0-mA, bi-frontal DLPFC montage, left anodal), over a span of two weeks. After completion, 10 additional open label sessions were offered. Tolerability, safety and compliance were evaluated. Preliminary clinical effects were measured with the fatigue severity scale (FSS). Result(s): A total of 18 participants completed 330 RS-tDCS sessions (Table1); one subject did not complete 10 optional sessions and one withdrew consent. Tolerability of 2.0 mA stimulation with <=6 on visual analog scale for pain (VAS-Pain) was 100%. Systematically recorded side effects were: tingling 22.4%, itching 8.2%, burning sensation 11.5%, dizziness 0.3%, headache 3.3%, sleepiness 0.3%, and nausea 0.9% (Figure1). No serious AEs were reported. Compliance was 100% as subjects completed all required visits with no attrition or interruptions. Preliminary fatigue clinical effects of 10 sessions showed a significant decrease of FSS (p < 0.05) only in the real RS-tDCS group (Figure2). Further analysis of 20 real RS-tDCS sessions (10 Rand_real +10 Open_label) showed a greater significant decrease in FSS (p < 0.05) (Figure2). Responders (>30% FSS improvement) were 44% after 10 RS-tDCS sessions and 62% after 20 sessions. Conclusion(s): At-home RS-tDCS therapy paired with CT is safe and well-tolerated by PD patients, with the advantages of ease of recruitment and subject compliance. Acceptability was achieved by easy setup and intuitive design of the device. At-home RS-tDCS therapy paired with CT shows potential to remediate fatigue symptoms in PD but the small sample size limits efficacy conclusions. Our paradigm may be influential in designing future studies that will facilitate clinical trials with a larger subject population and extended trial duration. Supported by Grant No. PDF-TRG-1722 from the Parkinson's Foundation.

BACKGROUND:, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. METHODS:, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. RESULTS:, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. CONCLUSIONS:Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.

The aim of this study was to conduct a systematic review of the literature and meta-analysis to estimate the association between psychophysiological activity and reactivity at baseline or after a psychological task with CP among children and adolescents. We systematically reviewed published studies reporting autonomic nervous system activity in youth with CP and meta-analyzed the relationship between CP and autonomic baseline as well as task-related reactivity in 66 studies (N = 10,227). Across 34 included case-control studies that were based on CP cut-off scores, we found a significant pooled effect for task related Skin-Conductance, Respiratory Sinus Arrhythmia, and cardiac Pre-Ejection Period, but no significant group differences for Heart Rate nor for any baseline measures. Findings suggested reduced parasympathetic and sympathetic reactivity to emotional tasks, pointing to co-inhibition of the two systems. However, across 32 studies with correlational design we only found a significant negative correlation of baseline and task-related heart rate with CP. The present meta-analysis derived several conclusions that have the potential to inform biological vulnerability models and biologically driven interventions.

The findings of neuroimaging studies in children/adolescents with ADHD, and even those of previous meta-analyses, are divergent. Here, Activation Likelihood Estimation meta-analysis, following the current best-practice guidelines, was conducted. We searched multiple databases and traced the references up to June 2018. Then, we extracted the reported coordinates reflecting group comparison between ADHD and healthy subjects from 96 eligible studies, containing 1914 unique participants. The analysis of pooled structural and functional, sub-analyses restricted to modality, and in-/decreased contrast did not yield any significant findings. However, further sub-analyses in the task-fMRI experiments (neutral stimuli only) led to aberrant activity in the left pallidum/putamen and decreased activity (male subjects only) in the left inferior frontal gyrus. The overall findings indicate a lack of regional convergence in children/adolescents with ADHD, which might be due to heterogeneous clinical populations, various experimental design, preprocessing, statistical procedures in individual publications. Our results highlight the need for further high-powered investigations, but may also indicate ADHD pathophysiology might rest in network interactions rather than just regional abnormality.

BACKGROUND:Body dysmorphic disorder (BDD) is a common disorder which is associated with a high rate of comorbidity and functional impairment. Although research shows that cognitive-behavioral therapy can be an efficacious treatment for BDD, there is growing evidence that dysregulated emotion is a core deficit. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders (UP) is a transdiagnostic, emotion focused cognitive-behavioral therapy protocol that has been developed to target emotion regulation processes that play an important role in the development and maintenance of many emotional disorders METHODS: : In the present study, 128 patients meeting criteria for BDD were randomized to either the UP (n = 64) or waitlist/treatment-as-usual (WL/TAU) condition. Diagnoses were determined using semi-structural interviews and patients also completed the Brown Assessment of Beliefs Scale (BABS), the Appearance Anxiety Inventory (AAI), the Difficulties in Emotion Regulation Scale (DERS), the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI). RESULTS:Repeated measure ANOVA indicated that the UP significantly decreased depression, BDD symptoms and body-related anxiety, as well as significantly improving emotional regulation all with large effect sizes compared to the TAU/WL condition. Treatment gains as well as remission of comorbid conditions were maintained at the three-month follow-up. LIMITATIONS:Our study limitations include restricted follow-up periods and excluding participants who were actively suicidal. CONCLUSIONS:To our knowledge, this is the first examination of the UP for BDD, and results suggest that this disorder shares common mechanisms with other disorders of emotion, and that the UP may be an additional efficacious treatment for this condition.

OBJECTIVE:/UNASSIGNED:The authors documented rates of sustained use of an evidence-based practice following training sponsored by New York State (NYS), and they identified clinician characteristics related to sustained use. METHODS:/UNASSIGNED:Clinicians (N=89) who were employed in licensed NYS Office of Mental Health agencies serving children and adolescents and who were trained to proficiency in Managing and Adapting Practice (MAP) in 2016 were contacted between 9 and 18 months later and asked whether they were still using (users) or had stopped using (nonusers) MAP and their reason for doing so. RESULTS:/UNASSIGNED:Responses were received from 57% of trainees and of those, 80% reported continued use of MAP. Score on the appeal subscale of the Evidence-Based Practices Attitude Scale (EBPAS) was the only significant difference between users and nonusers. CONCLUSIONS:/UNASSIGNED:Most clinicians reported sustained use of MAP. The EBPAS appeal subscale can be used to identify clinicians who are likely to discontinue use.