Search

Abstract To conduct a systematic review of the comparative efficacy of various psychotropic medications for the treatment of disruptive behavior (DBs) in youths. To this aim, we systematically reviewed randomized clinical trials (RCTs) of various psychotropic medications targeting symptoms of DBs and applied network meta-analysis to investigate their relative efficacy. Fifty-five RCTs meeting the inclusion criteria were selected. To predict and interpret relative treatment efficacy, we compared the efficacy of various psychotropic medications prescribed for DB symptoms based on their mechanism of action. Network meta-analysis revealed that for reducing DBs, second-generation antipsychotics, stimulants, and non-stimulant ADHD medications were more efficacious than placebo, and second-generation antipsychotics were the most efficacious. The dopaminergic modulation of top-down inhibitory process by these medications is discussed in this review. This study offers information on the relative efficacy of various psychotropic medications for the treatment of DB, and insight into a potential neurobiological underpinning for those symptoms. It also illustrates the potential utility of these neurobiological mechanisms as a target for future treatment studies.

Abstract Alcohol and cannabis use disorder (AUD/CUD) are two of the most common addictive disorders. While studies are beginning to understand the neural changes related to acute and chronic use, few studies have examined the independent effects of AUD and CUD on neural oscillatory activity. We examined 45 adults who reported current use of both cannabis and alcohol. Participants underwent the SCID-V to determine whether they met criteria for AUD and/or CUD. Participants also completed a visual-spatial processing task while undergoing magnetoencephalography (MEG). ANCOVA with a 2 × 2 design was then used to identify the main effects of AUD and CUD on source-level oscillatory activity. Of the 45 adults, 17 met criteria for AUD, and 26 met criteria for CUD. All participants, including comparison groups, reported use of both cannabis and alcohol. Statistical analyses showed a main effect of AUD, such that participants with AUD displayed a blunted occipital alpha (8–16 Hz) response. Post-hoc testing showed this decreased alpha response was related to increased AUD symptoms, above and beyond amount of use. No effects of AUD or CUD were identified in visual theta or gamma activity. In conclusion, AUD was associated with reduced alpha responses and scaled with increasing severity, independent of CUD. These findings indicate that alpha oscillatory activity may play an integral part in networks affected by alcohol addiction.

Background: Spontaneous beta activity in the primary motor cortices has been shown to increase in amplitude with advancing age, and that such increases are tightly coupled to stronger motor-related beta oscillations during movement planning. However, the relationship between these age-related changes in spontaneous beta in the motor cortices, local cortical thickness, and overall motor function remains unclear. Methods: We collected resting-state magnetoencephalography (MEG), high-resolution structural MRI, and motor function scores using a neuropsychological battery from 126 healthy adults (56 female; age range = 22–72 years). MEG data were source-imaged and a whole-brain vertex-wise regression model was used to assess age-related differences in spontaneous beta power across the cortex. Cortical thickness was computed from the structural MRI data and local beta power and cortical thickness values were extracted from the sensorimotor cortices. To determine the unique contribution of age, spontaneous beta power, and cortical thickness to the prediction of motor function, a hierarchical regression approach was used. Results: There was an increase in spontaneous beta power with age across the cortex, with the strongest increase being centered on the sensorimotor cortices. Sensorimotor cortical thickness was not related to spontaneous beta power, above and beyond age. Interestingly, both cortical thickness and spontaneous beta power in sensorimotor regions each uniquely contributed to the prediction of motor function when controlling for age. Discussion: This multimodal study showed that cortical thickness and spontaneous beta activity in the sensorimotor cortices have dissociable contributions to motor function across the adult lifespan. These findings highlight the complexity of interactions between structure and function and the importance of understanding these interactions in order to advance our understanding of healthy aging and disease.

Abstract Adolescence is a critical period for the development and refinement of several higher-level cognitive functions, including visual selective attention. Clinically, it has been noted that adolescents with cerebral palsy (CP) may have deficits in selectively attending to objects within their visual field. This study aimed to evaluate the neural oscillatory activity in the ventral attention network while adolescents with CP performed a visual selective attention task. Adolescents with CP (N = 14; Age = 15.7 ± 4 years; MACS I–III; GMFCS I–IV) and neurotypical (NT) adolescents (N = 21; Age = 14.3 ± 2 years) performed the Eriksen flanker task while undergoing magnetoencephalographic (MEG) brain imaging. The participants reported the direction of a target arrow that was surrounded by congruent or incongruent flanking arrows. Compared with NT adolescents, adolescents with CP had slower responses and made more errors regarding the direction of the target arrow. The MEG results revealed that adolescents with CP had stronger alpha oscillations in the left insula when the flanking arrows were incongruent. Furthermore, participants that had more errors also tended to have stronger alpha oscillatory activity in this brain region. Altogether these results indicate that the aberrant activity seen in the left insula is associated with diminished visual selective attention function in adolescents with CP.

Background: While numerous studies have examined the developmental trajectory of task-based neural oscillations during childhood and adolescence, far less is known about the evolution of spontaneous cortical activity during this time period. Likewise, many studies have shown robust sex differences in task-based oscillations during this developmental period, but whether such sex differences extend to spontaneous activity is not understood. Methods: Herein, we examined spontaneous cortical activity in 111 typically-developing youth (ages 9–15 years; 55 male). Participants completed a resting state magnetoencephalographic (MEG) recording and a structural MRI. MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially-specific effects of age, sex, and their interaction. Results: We found robust increases in power with age in all frequencies except delta, which decreased over time, with findings largely confined to frontal cortices. Sex effects were distributed across frontal and temporal regions; females tended to have greater delta and beta power, whereas males had greater alpha. Importantly, there was a significant age-by-sex interaction in theta power, such that males exhibited decreasing power with age while females showed increasing power with age in the bilateral superior temporal cortices. Discussion: These data suggest that the strength of spontaneous activity undergoes robust change during the transition from childhood to adolescence (i.e., puberty onset), with intriguing sex differences in some cortical areas. Future developmental studies should probe task-related oscillations and spontaneous activity in parallel.

Introduction: Resting-state oscillatory activity has been extensively studied across a wide array of disorders. Establishing which spectrally- and spatially-specific oscillatory components exhibit test-retest reliability is essential to move the field forward. While studies have shown short-term reliability of MEG resting-state activity, no studies have examined test-retest reliability across an extended period of time to establish the stability of these signals, which is critical for reproducibility. Methods: We examined 18 healthy adults age 23 - 61 who completed three visits across three years. For each visit, participants completed both a resting state MEG and structural MRI scan. MEG data were source imaged, and the cortical power in canonical frequency bands (delta, theta, alpha, beta, low gamma, high gamma) was computed. Intra-class correlation coefficients (ICC) were then calculated across the cortex for each frequency band. Results: Over three years, power in the alpha and beta bands displayed the highest reliability estimates, while gamma showed the lowest estimates of three-year reliability. Spatially, delta, alpha, and beta all showed the highest degrees of reliability in the parietal cortex. Interestingly, the peak signal for each of these frequency bands was located outside of the parietal cortex, suggesting that reliability estimates were not solely dependent on the signal-to-noise ratio. Conclusion: Oscillatory resting-state power in parietal delta, posterior beta, and alpha across most of the cortex are reliable across three years and future MEEG studies may focus on these measures for the development of specific markers.

Successful interaction with one’s visual environment is paramount to developing and performing many basic and complex mental functions. Although major aspects of visual development are completed at an early age, other structural and functional components of visual processing appear to be dynamically changing across a much more protracted period extending into late childhood and adolescence. However, the underlying neurophysiological changes and cortical oscillatory dynamics that support maturation of the visual system during this developmental period remain poorly understood. The present study utilized magnetoencephalography (MEG) to investigate maturational changes in the neural dynamics serving basic visual processing during childhood and adolescence (ages 9–15, n = 69). Our key results included robust sex differences in alpha oscillatory activity within the left posterior parietal cortex, and sex-by-age interactions in gamma activity in the right lingual gyrus and superior parietal lobule. Hierarchical regression revealed that the peak frequency of both the alpha and gamma responses predicted response power in parietal regions above and beyond the noted effects of age and sex. These findings affirm the view that neural oscillations supporting visual processing develop over a much more protracted period, and illustrate that these maturational trajectories are influenced by numerous elements, including age, sex, and individual variation.

Background: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses. Methods: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could accurately distinguish the three groups using linear discriminant analysis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, area under the curve (AUC), and accuracy were computed for each model using the classification results based on GMV compared to the neuropsychological assessment. Results: The best performing model was comprised of bilaterally combined GMV and was stratified by sex. Among males, sensitivity was 85.2% (95% CI: 66.3%–95.8%), specificity was 97.0% (95% CI: 91.6%-99.4%), and the AUC was 0.91 (95% CI: 0.83–0.99). Among females, sensitivity was 100.0% (95% CI: 83.9%–100.0%), specificity was 98.8% (95% CI: 93.4%-100.0%), and the AUC was 0.99 (95% CI: 0.98–1.00). Conclusions: GMV accurately discriminated HAND from unimpaired PWH and controls. Measures of GMV may be highly sensitive to HAND, and revisions to the Frascati criteria should consider including GMV in conjunction with a neuropsychological assessment to diagnose HAND.

Background: Despite living a normal lifespan, at least 35% of persons with HIV (PWH) in resource-rich countries develop HIV-associated neurocognitive disorder (HAND). This high prevalence of cognitive decline may reflect accelerated ageing in PWH, but the evidence supporting an altered ageing phenotype in PWH has been mixed. Methods: We examined the impact of ageing on the orienting of visual attention in PWH using dynamic functional mapping with magnetoencephalography (MEG) in 173 participants age 22–72 years-old (94 uninfected controls, 51 cognitively-unimpaired PWH, and 28 with HAND). All MEG data were imaged using a state-of-the-art beamforming approach and neural oscillatory responses during attentional orienting were examined for ageing, HIV, and cognitive status effects. Findings: All participants responded slower during trials that required attentional reorienting. Our functional mapping results revealed HIV-by-age interactions in left prefrontal theta activity, alpha oscillations in the left parietal, right cuneus, and right frontal eye-fields, and left dorsolateral prefrontal beta activity (p

Background Proprietary spearmint extract (PSE) containing a minimum 14.5% rosmarinic acid and 24% total phenolic content, has evinced positive effects on cognition in individuals aged 50–70 with memory impairment after chronic supplementation. To address the growing interest in connecting mental and physical performance, the present study examined whether the nootropic effects of PSE translate into changes in reactive agility following daily supplementation with PSE. Methods Utilizing a randomized, double-blind, placebo-controlled, parallel design, healthy, recreationally-active men and women (n = 142) received 900 mg of PSE or placebo (PLA) daily for 90 days. Reactive agility, our primary outcome, was determined by measuring the number of hits and average reaction time (ART) on a Makoto Arena II, a 3600 audio-visual device that measures stationary, lateral, and multi-directional active choice reaction performance. Safety was evaluated using complete blood count, comprehensive metabolic panel, and blood lipids. Measurements were evaluated on days 7, 30, and 90 of supplementation. Results An overall treatment effect (p = 0.019) was evident for increased hits with PSE on the stationary test with footplates, with between group differences at Day 30 (PSE vs. PLA: 28.96 ± 2.08 vs. 28.09 ± 1.92 hits; p = 0.040) and Day 90 (PSE vs. PLA: 28.42 ± 2.54 vs. 27.02 ± 3.55 hits; p = 0.002). On the same task, ART improved (treatment effect, p = 0.036) with PSE at Day 7 (PSE vs. PLA: 0.5896 ± 0.060 vs. 0.6141 ± 0.073 s; p = 0.049) and Day 30 (PSE vs. PLA: 0.5811 ± 0.068 vs. 0.6033 ± 0.055 s; p = 0.049). PSE also significantly increased hits (treatment effect, p = 0.020) at Day 30 (PSE vs. PLA: 19.25 ± 1.84 vs. 18.45 ± 1.48 hits; p = 0.007) and Day 90 (PSE vs. PLA: 19.39 ± 1.90 vs. 18.66 ± 1.64 hits; p = 0.026) for the multi-directional test with footplates. Significant differences were not observed in the remaining Makoto tests. PSE was well tolerated as evidenced by no effects observed in the blood safety panels. Conclusions The findings of the current study demonstrate that consumption of 900 mg of PSE improved specific measures of reactive agility in a young, active population. Trial registration clinicaltrials.gov, NCT02518165. Registered August 7, 2015 – retrospectively registered.