Disrupted white matter connectivity and organization of brain structural connectomes in tuberous sclerosis complex patients with neuropsychiatric disorders using diffusion tensor imaging

Objective: Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome with variable and unpredictable neurological comorbidity that includes epilepsy, intellectual disability (ID), autism spectrum disorder, and neurobehavioral abnormalities. The degree of white matter involvement is believed to be associated with the severity of neurological impairment. The goal of the present study was to evaluate diffusion characteristics of tubers, white matter lesions, and brain structural network alterations in TSC patients using diffusion tensor imaging (DTI), graph theoretical analysis (GTA), and network-based statistical (NBS) analysis.

Materials and methods: Forty-two patients with a definitive diagnosis of TSC were recruited for this study. All patients underwent brain DTI examination using a 3 T magnetic resonance imaging system. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) values, and fractional anisotropy (FA) mapping in 52 tubers and white matter lesions were measured and compared with those of contralateral normal regions. GTA was performed on the inter-regional connectivity matrix, and NBS analysis was used to identify the significance of any connected subnetworks evident in the set of altered connections. For neurological severity subgrouping, a neurological severity score was assigned to TSC patients including those with ID, seizure, autism, and other neuropsychiatric disorders (NPDs).

Results: Significantly higher MD, AD, and RD, and lower FA values, were found in TSC lesions compared with those measured in contralateral normal regions for tubers (P < 0.05). GTA and NBS analysis provided better local segregation but worse global integration of the structural network (regular-like network) in TSC patients with ID, seizure, and higher Neurological Severity Score. Disrupted subnetworks in TSC patients with severe status included connections from the frontal lobe to the parietal lobe, temporal lobe to the caudate, and temporal lobe to the insula.

Discussion: DTI has the potential to provide valuable information about cytoarchitectural changes in TSC lesions beyond morphological MRI findings alone. Using GTA and NBS, current results provide the information of disrupted white matter connectivity and organization in TSC patients with different neuropsychological impairments.