Resting‐State fMRI Networks in Children with Tuberous Sclerosis Complex

Abstract

BACKGROUND AND PURPOSE:There are no published studies examining resting state networks (RSNs) and their relationship with neurodevelopmental metrics in tuberous sclerosis complex (TSC). We aimed to identify major resting-state functional magnetic resonance imaging (rs-fMRI) networks in infants with TSC and correlate network analyses with neurodevelopmental assessments, autism diagnosis, and seizure history. METHODS: Rs-fMRI data from 34 infants with TSC, sedated with propofol during the scan, were analyzed to identify auditory, motor, and visual RSNs. We examined the correlations between auditory, motor, and visual RSNs at approximately 11.5 months, neurodevelopmental outcome at approximately 18.5 months, and diagnosis of autism spectrum disorders at approximately 36 months of age. RESULTS: RSNs were obtained in 76.5% (26/34) of infants. We observed significant negative correlations between auditory RSN and auditory comprehension test scores (p = .038; r = −.435), as well as significant positive correlations between motor RSN and gross motor skills test scores (p = .023; r = .564). Significant positive correlations between motor RSNs and gross motor skills (p = .012; r = .754) were observed in TSC infants without autism, but not in TSC infants with autism, which could suggest altered motor processing. There were no significant differences in RSNs according to seizure history. CONCLUSIONS: Negative correlation between auditory RSN, as well as positive correlation between motor RSN and developmental outcome measures might reflect different brain mechanisms and, when identified, may be helpful in predicting later function. A larger study of TSC patients with a healthy control group is needed before auditory and motor RSNs could be considered as neurodevelopmental outcome biomarkers.

Neuroimaging in tuberous sclerosis complex

“…The evidence of impaired brain connectivity and subtle white matter abnormalities in TSC has broadly confirmed this thesis, with DTI and resting state fMRI (RS-fMRI) suggesting a widespread alteration in axonal organisation and myelination [48]. In particular, two RS-fMRI studies showed the presence of significant differences in functional connectivity between TSC patients and healthy controls, with a more prominent involvement of auditory and motor networks [49,50]. The evidence of altered structural connectivity further validated these functional findings.…”

mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity

“…Future applications of the cross-species, multiscale research platform we describe here might help unravel the connectional heterogeneity of ASD by permitting the identification of ASD subtypes 2 . Future case-control imaging investigations of individuals harboring Tsc2 mutations 76 might also crucially help test the validity of our predictions and their mechanistic significance in relevant patient populations.…”

Assessment of disrupted brain functional connectome in tuberous sclerosis complex using resting-state fMRI

“…TSC patients with neuropsychiatric comorbidities had lower structural connectivity. [15,16] To approach models regarding the complex network of brain connectivity, here we intend to apply a graph using the nodes and interconnecting edges to provide measures of whole-brain functional connectivity. [17] The aim is to use resting-state functional connectivity to provide the first findings on the disrupted functional brain networks of TSC patients using graph theoretical analysis (GTA) and network-based statistic (NBS) analysis.…”