Amelioration of Anxiety Associated with Opioid Withdrawal by Activation of Spinal Mechanoreceptors Via Novel Heterodyned Whole Body Vibration.

Objectives: Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD. Methods: Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge. Results: In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10-7). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10-3). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment. Conclusions: These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.

Gender-Specific Interactions in a Visual Object Recognition Task in Persons with Opioid Use Disorder.

Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men reported at twice the rate for women. Using a controlled, cross-sectional, age-matched (18-56 y) design to better understand the cognitive neuroscience of OUD, we evaluated the electroencephalographic (EEG) responses of male and female participants with OUD vs. age- and gender-matched non-OUD controls during a simple visual object recognition Go/No-Go task. Overall, women had significantly slower reaction times (RTs) than men. In addition, EEG N200 and P300 event-related potential (ERP) amplitudes for non-OUD controls were significantly larger for men, while their latencies were significantly shorter than for women. However, while N200 and P300 amplitudes were not significantly affected by OUD for either men or women in this task, latencies were also affected differentially in men vs. women with OUD. Accordingly, for both N200 and P300, male OUD participants exhibited longer latencies while female OUD participants exhibited shorter ones than in non-OUD controls. Additionally, robust oscillations were found in all participants during a feedback message associated with performance in the task. Although alpha and beta power during the feedback message were significantly greater for men than women overall, both alpha and beta oscillations exhibited significantly lower power in all participants with OUD. Taken together, these findings suggest important gender by OUD differences in cognitive processing and reflection of performance in this simple visual task.

Methylphenidate Treatment of Cognitive Dysfunction in Adults After Mild to Moderate Traumatic Brain Injury: Rationale, Efficacy, and Neural Mechanisms.

Positive effects of methylphenidate (MPH) on attention and cognitive processing speed have been reported in studies of patients with moderate to severe traumatic brain injury (TBI). Studies which have acquired functional brain imaging before and while using MPH have also found alteration of brain activation while performing a cognitive task; in some studies, this alteration of activation in selective brain regions was also related to improved performance on cognitive tests administered outside of the scanning environment. Enhanced cognitive performance has been reported after single doses of MPH and after daily treatment over durations of up to and exceeding 1 month. Preclinical research and both positron emission tomography and single photon emission tomography of humans have shown that MPH increases extracellular dopamine and norepinephrine; the dose effects of MPH have an inverted U-shaped function where high doses may cause insomnia, nervousness, and increased heart rate among other symptoms and impair cognitive performance, whereas too low a dose fails to improve cognitive performance. In the past 5 years, small clinical trials, and experimental pilot studies have found therapeutic effects of single and repeated low doses of MPH in patients with mild TBI who reported cognitive dysfunction. This literature also suggests that MPH may interact with concurrent cognitive interventions to enhance their effects. This focused review will critically evaluate the recent literature on MPH effects on cognitive dysfunction after mild to moderate TBI. To elucidate the neural mechanisms of MPH effects, this review will also include recent imaging research, preclinical, and experimental human studies.

Persistent Disruption of Brain Connectivity after Sports-Related Concussion in a Female Athlete.

Structural and functional connectivity (FC) after sports-related concussion (SRC) may remain altered in adolescent athletes despite symptom resolution. Little is known, however, about how alterations in structural connectivity and FC co-present in female athletes whose symptom recovery tends to be prolonged. Despite resolution of symptoms, one month after her second SRC, an 18-year-old female athlete had decreased structural connectivity in the corpus callosum and cingulum, with altered FC near those regions, compared with other SRC and orthopedically injured athletes. Findings show persistent effects of SRC on advanced brain imaging and the possibility of greater vulnerability of white matter tracts in females.

Heterogeneity of brain lesions in pediatric traumatic brain injury.

OBJECTIVE: Magnetic resonance imaging (MRI) provides a method to identify and quantify abnormalities resulting from traumatic brain injury (TBI). MRI abnormalities in children with TBI have not been fully characterized according to the frequency, location, and quantitative measurement of a range of pathologies critical for studies of neuropsychological outcome. Here, we report MRI findings from a large, multicenter study of childhood TBI, the Social Outcomes of Brain Injury in Kids (SOBIK) study, which compared qualitative and quantitative neuroimaging findings in 72 children with complicated mild-to-severe TBI to 52 children with orthopedic injury (OI). METHOD: Qualitative analyses of MRI scans coded white matter hyperintensities (WMHs), hemosiderin deposits reflecting prior hemorrhagic lesions, regions of encephalomalacia and/or atrophy, and corpus callosum atrophy and traumatic shear lesions. Two automated quantitative analyses were conducted: (a) FreeSurfer methods computed volumes for total brain, white matter (WM), gray matter (GM), corpus callosum, ventricles, amygdala, hippocampus, basal ganglia, and thalamus along with a ventricle-to-brain ratio (VBR); and (b) voxel-based morphometry (VBM) to identify WM, GM, and cerebrospinal fluid. We also examined performance on the Processing Speed Index (PSI) from the Wechsler Intelligence Scale for Children, Fourth Edition, in relation to the above-mentioned neuroimaging variables. RESULTS: WMHs, hemosiderin deposits, and focal areas of encephalomalacia or atrophy were common in children with TBI, were related to injury severity, and were mostly observed within a frontotemporal distribution. Quantitative analyses showed volumetric changes related to injury severity, especially ventricular enlargement and reduced corpus callosum volume. VBM demonstrated similar findings, but, in addition, GM reductions in the inferior frontal, basal forebrain region, especially in the severe TBI group. The complicated mild TBI group showed few differences from the OI group. PSI was significantly associated with global atrophy, as measured by VBR. CONCLUSION: MRI findings after childhood TBI are diverse and particularly influenced by injury severity, and they involve common features, group heterogeneity, and individual variability.