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.

Keywords: Autism spectrum disorders; propofol; resting state functional resonance imaging; resting state networks; tuberous sclerosis complex.

Figure 1.

Auditory resting state network (RSN) (top panel), Motor RSN (middle panel), and Medial Visual RSN (bottom panel) of a child with tuberous sclerosis complex (aged 15 months 28 days at the time of MRI scan). P = posterior, A = anterior, R = right, L = left.

Figure 2.

Scatterplot depicting the results of the correlational analysis between the Auditory resting state network (RSN) z-scores (y axis) and Auditory Comprehension skills standard scores as measured by the Preschool Language Scales-5 (x axis), for the tuberous sclerosis complex patients where an auditory RSN was observed.

Figure 3.

Scatterplot depicting the results of the correlational analysis between the Motor resting state network (RSN) z-scores (y axis) and Gross Motor Skills T-scores as measured by Mullen Early Scales of Learning (x axis), for the tuberous sclerosis complex patients where a motor RSN was observed.

Figure 4.

Scatterplot depicting the results of the correlational analysis between the Motor resting state network (RSN) z-scores (y axis) and Gross Motor Skills T-scores as measured by Mullen Early Scales of Learning (x axis), for the tuberous sclerosis complex patients without autism spectrum disorders diagnosis where a motor RSN was observed.