The Differential Effects of Adiposity and Fitness on Functional Connectivity in Preadolescent Children.

PURPOSE: Childhood obesity is a global health concern, with >340 million youth considered overweight or obese. In addition to contributing greatly to health care costs, excess adiposity associated with obesity is considered a major risk factor for premature mortality from cardiovascular and metabolic diseases and is also negatively associated with cognitive and brain health. A complementary line of research highlights the importance of cardiorespiratory fitness, a by-product of engaging in physical activity, on an abundance of health factors, including cognitive and brain health. METHODS: This study investigated the relationship among excess adiposity (visceral adipose tissue [VAT], subcutaneous abdominal adipose tissue), total abdominal adipose tissue, whole-body percent fat [WB%FAT], body mass index (BMI), and fat-free cardiorespiratory fitness (FF-V̇O 2max ) on resting-state functional connectivity (RSFC) in 121 ( f = 68) children (7-11 yr) using a data-driven whole-brain multivoxel pattern analysis. RESULTS: Multivoxel pattern analysis revealed brain regions that were significantly associated with VAT, BMI, WB%FAT, and FF-V̇O 2 measures. Yeo's (2011) RSFC-based seven-network cerebral cortical parcellation was used for labeling the results . Post hoc seed-to-voxel analyses found robust negative correlations of VAT and BMI with areas involved in the visual, somatosensory, dorsal attention, ventral attention, limbic, frontoparietal, and default mode networks. Further, positive correlations of FF-V̇O 2 were observed with areas involved in the ventral attention and frontoparietal networks. These novel findings indicate that negative health factors in childhood may be selectively and negatively associated with the 7 Yeo-defined functional networks, yet positive health factors (FF-V̇O 2 ) may be positively associated with these networks. CONCLUSIONS: These novel results extend the current literature to suggest that BMI and adiposity are negatively associated with, and cardiorespiratory fitness (corrected for fat-free mass) is positively associated with, RSFC networks in children.

Resting-State Functional Connectivity and Scholastic Performance in Preadolescent Children: A Data-Driven Multivoxel Pattern Analysis (MVPA).

Scholastic performance is the key metric by which schools measure student's academic success, and it is important to understand the neural-correlates associated with greater scholastic performance. This study examines resting-state functional connectivity (RsFc) associated with scholastic performance (reading and mathematics) in preadolescent children (7-9 years) using an unbiased whole-brain connectome-wide multi-voxel pattern analysis (MVPA). MVPA revealed four clusters associated with reading composite score, these clusters were then used for whole-brain seed-based RsFc analysis. However, no such clusters were found for mathematics composite score. Post hoc analysis found robust associations between reading and RsFc dynamics with areas involved with the somatomotor, dorsal attention, ventral attention, limbic, frontoparietal, and default mode networks. These findings indicate that reading ability may be associated with a wide range of RsFc networks. Of particular interest, anticorrelations were observed between the default mode network and the somatomotor, dorsal attention, ventral attention, and frontoparietal networks. Previous research has demonstrated the importance of anticorrelations between the default mode network and frontoparietal network associated with cognition. These results extend the current literature exploring the role of network connectivity in scholastic performance of children.

Neurodevelopmental and Psychiatric Symptoms in Patients with a Cyst Compressing the Cerebellum: an Ongoing Enigma.

A patient diagnosed with developmental delay, intellectual disability, and autistic and obsessive-compulsive symptoms was found to have a posterior fossa arachnoid cyst (PFAC) compressing the cerebellum. The patient was referred to our Ataxia Unit for consideration of surgical drainage of the cyst to improve his clinical constellation. This scenario led to an in-depth analysis including a literature review, functional resting-state MRI analysis of our patient compared to a group of controls, and genetic testing. While it is reasonable to consider that there may be a causal relationship between PFAC and neurodevelopmental or psychiatric symptoms in some patients, there is also a nontrivial prevalence of PFAC in the asymptomatic population and a significant possibility that many PFAC are incidental findings in the context of primary cognitive or psychiatric symptoms. Our functional MRI analysis is the first to examine brain function, and to report cerebellar dysfunction, in a patient presenting with cognitive/psychiatric symptoms found to have a structural abnormality compressing the cerebellum. These neuroimaging findings are inherently limited due to their correlational nature but provide unprecedented evidence suggesting that cerebellar compression may be associated with cerebellar dysfunction. Exome gene sequencing revealed additional etiological possibilities, highlighting the complexity of this field of cerebellar clinical and scientific practice. Our findings and discussion may guide future investigations addressing an important knowledge gap-namely, is there a link between cerebellar compression (including arachnoid cysts and possibly other forms of cerebellar compression such as Chiari malformation), cerebellar dysfunction (including fMRI abnormalities reported here), and neuropsychiatric symptoms?

Atypical behaviour and connectivity in SHANK3-mutant macaques.

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.

Resting-state anticorrelations between medial and lateral prefrontal cortex: association with working memory, aging, and individual differences.

We examined how variation in working memory (WM) capacity due to aging or individual differences among young adults is associated with intrinsic or resting-state anticorrelations, particularly between (1) the medial prefrontal cortex (MPFC), a component of the default-mode network (DMN) that typically decreases in activation during external, attention-demanding tasks, and (2) the dorsolateral prefrontal cortex (DLPFC), a component of the fronto-parietal control network that supports executive functions and WM and typically increases in activation during attention-demanding tasks. We compared the magnitudes of MPFC-DLPFC anticorrelations between healthy younger and older participants (Experiment 1) and related the magnitudes of these anticorrelations to individual differences on two behavioral measures of WM capacity in two independent groups of young adults (Experiments 1 and 2). Relative to younger adults, older adults exhibited reductions in WM capacity and in MPFC-DLPFC anticorrelations. Within younger adults, greater MPFC-DLPFC anticorrelation at rest correlated with greater WM capacity. These findings show that variation in MPFC-DLPFC anticorrelations, whether related to aging or to individual differences, may reflect an intrinsic functional brain architecture supportive of WM capacity.