Faculty Bibliography

OBJECTIVE:Impaired multisensory integration in autism spectrum disorder (ASD) may arise from functional dysconnectivity among brain systems. Our study examines the functional connectivity integration between primary modal sensory regions and heteromodal processing cortex in ASD, and whether abnormalities in network integration relate to clinical severity. METHOD/METHODS:We studied a sample of 55 high-functioning ASD and 64 healthy controls (HC) male children and adolescents (total n = 119, age range 7-18). Stepwise functional connectivity analysis (SFC) was applied to resting state functional magnetic resonance images (rsfMRI) to characterize the connectivity paths that link primary sensory cortices to higher-order brain cognitive functional circuits and relate alterations in functional connectivity integration with three clinical scales: Social Communication Questionnaire, Social Responsiveness Scale, and Vineland Adaptive Behavior Scales. RESULTS:HC displayed typical functional connectivity transitions from primary sensory systems to association areas, but the ASD group showed altered patterns of multimodal sensory integration to heteromodal systems. Specifically, compared to the HC group, the ASD group showed (1) hyper-connectivity in visual cortex at initial link step distances; (2) hyper-connectivity between sensory unimodal regions and regions of the default mode network; and (3) hypo-connectivity between sensory unimodal regions and areas of the fronto-parietal and attentional networks. These patterns of hyper- and hypo-connectivity were associated with increased clinical severity in ASD. CONCLUSION/CONCLUSIONS:Network-wise reorganization in high-functioning ASD individuals affects strategic regions of unimodal-to-heteromodal cortical integration predicting clinical severity. Additionally, SFC analysis appears to be a promising approach for studying the neural pathophysiology of multisensory integration deficits in ASD.

BACKGROUND:Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach. METHODS:Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels. RESULTS:). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients. CONCLUSIONS:Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

Brain growth charts and age-normed brain templates are essential resources for researchers to eventually contribute to the care of individuals with atypical developmental trajectories. The present work generates age-normed brain templates for children and adolescents at one-year intervals and the corresponding growth charts to investigate the influences of age and ethnicity using a common pediatric neuroimaging protocol. Two accelerated longitudinal cohorts with the identical experimental design were implemented in the United States and China. Anatomical magnetic resonance imaging (MRI) of typically developing school-age children (TDC) was obtained up to three times at nominal intervals of 1.25 years. The protocol generated and compared population- and age-specific brain templates and growth charts, respectively. A total of 674 Chinese pediatric MRI scans were obtained from 457 Chinese TDC and 190 American pediatric MRI scans were obtained from 133 American TDC. Population- and age-specific brain templates were used to quantify warp cost, the differences between individual brains and brain templates. Volumetric growth charts for labeled brain network areas were generated. Shape analyses of cost functions supported the necessity of age-specific and ethnicity-matched brain templates, which was confirmed by growth chart analyses. These analyses revealed volumetric growth differences between the two ethnicities primarily in lateral frontal and parietal areas, regions which are most variable across individuals in regard to their structure and function. Age- and ethnicity-specific brain templates facilitate establishing unbiased pediatric brain growth charts, indicating the necessity of the brain charts and brain templates generated in tandem. These templates and growth charts as well as related codes have been made freely available to the public for open neuroscience (https://github.com/zuoxinian/CCS/tree/master/H3/GrowthCharts).

Meditation is a type of mental training commonly applied in clinical settings and also practiced for general well-being. Brain functional connectivity (FC) patterns associated with meditation have revealed its brain mechanisms. However, the variety of FC methods applied has made it difficult to identify brain communication patterns associated with meditation. Here we carried out a coordinate-based meta-analysis to get preliminary evidence of meditation effects on changing brain network interactions. Fourteen seed-based, voxel-wise FC studies reported in 13 publications were reviewed; 10 studies with seeds in the default mode network (DMN) were meta-analyzed. Seed coordinates and the effect sizes in statistically significant regions were extracted, based on 170 subjects in meditation groups and 163 subjects in control groups. Seed-based d-mapping was used to analyze meditation versus control FC differences with DMN seeds. Meditation was associated with increased connectivity within DMN and between DMN and somatomotor network and with decreased connectivity between DMN and frontoparietal network (FPN) as well as ventral attention network (VAN). The pattern of decreased within-DMN FC and increased between-network FC (FPN and DAN with DMN) was more robust in highly experienced meditators compared to less experienced individuals. The identified neural network interactions may also promote meditation's effectiveness in clinical interventions for treating physical and mental disorders.

In the above published article there was an error in the abstract, the sentence should read as follows: "Meditation was associated with decreased connectivity within DMN and between DMN and somatomotor network and with increased connectivity between DMN and frontoparietal network (FPN) as well as ventral attention network (VAN)." The authors apologise for this error.

Background: Reduced endocannabinoid "tone" has been posited in the pathophysiology of ASD animal models; children with ASD have been found to have lower peripheral endocannabinoid levels. Additionally, anecdotal reports suggest cannabinoids may be beneficial for some aspects of ASD.
Method(s): Double-blind placebo-controlled comparison (NCT02956226) of whole plant cannabis extract containing cannabidiol (CBD) and DELTA9-tetrahydrocannabinol (THC) in a 20:1 ratio and (2) purified CBD and THC in the same ratio. Participants were 150 children and adolescents with ASD, both males (80%) and females (mean age 11.8 +/-4.1 yrs). They received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout, and crossed-over to receive another treatment for 12 weeks to further assess tolerability.
Result(s): There were no treatment related severe or serious adverse events. None of the outcomes differed significantly between cannabinoid preparation, in either treatment period. Considering cannabinoids together, in the first period, 43% of 90 children who received cannabinoids were either much or very much improved on the CGI-I compared with 21% of 47 on placebo (p = 0.009). Placebo-cannabinoid differences were not significant on the other primary outcome, the Home Situations Questionnaire for ASD (HSQ-ASD). A positive response on the Social Responsiveness Scale-2 (SRS-2) was defined as 15% decrease or better from baseline. In the first treatment period, 44% of participants who received cannabinoids had a positive response compared with 19% on placebo (p = 0.013). In terms of possible mediators of treatment effects on the SRS-2, male sex and milder ASD symptoms at baseline were independently associated with better response to cannabinoid treatment.
Conclusion(s): Novel pharmacological treatments for the core and comorbid symptoms of ASD are urgently needed. Preclinical studies implicate the endocannabinoid system in the pathophysiology of ASD. In a controlled study of 150 children, a combination of CBD and THC, in a 20:1 ratio, either as a whole plant extract or as pure cannabinoids, improved disruptive behaviors and an index of ASD core symptoms, with relatively few adverse events. These data suggest that further investigation of cannabinoids in ASD is likely to be promising