Independent contribution of individual white matter pathways to language function in pediatric epilepsy patients.
OBJECTIVE
Patients with epilepsy and malformations of cortical development (MCDs) are at high risk for language and other cognitive impairment. Specific impairments, however, are not well correlated with the extent and locale of dysplastic cortex; such findings highlight the relevance of aberrant cortico-cortical interactions, or connectivity, to the clinical phenotype. The goal of this study was to determine the independent contribution of well-described white matter pathways to language function in a cohort of pediatric patients with epilepsy.


METHODS
Patients were retrospectively identified from an existing database of pediatric epilepsy patients with the following inclusion criteria: 1. diagnosis of MCDs, 2. DTI performed at 3 T, and 3. language characterized by a pediatric neurologist. Diffusion Toolkit and Trackvis (http://www.trackvis.org) were used for segmentation and analysis of the following tracts: corpus callosum, corticospinal tracts, inferior longitudinal fasciculi (ILFs), inferior fronto-occipital fasciculi (IFOFs), uncinate fasciculi (UFs), and arcuate fasciculi (AFs). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated for each tract. Wilcoxon rank sum test (corrected for multiple comparisons) was used to assess potential differences in tract parameters between language-impaired and language-intact patients. In a separate analysis, a machine learning algorithm (random forest approach) was applied to measure the independent contribution of the measured diffusion parameters for each tract to the clinical phenotype (language impairment). In other words, the importance of each tract parameter was measured after adjusting for the contribution of all other tracts.


RESULTS
Thirty-three MCD patients were included (age range: 3-18 years). Twenty-one patients had intact language, twelve had language impairment. All tracts were identified bilaterally in all patients except for the AF, which was not identified on the right in 10 subjects and not identified on the left in 11 subjects. MD and/or FA within the left AF, UF, ILF, and IFOF differed between language-intact and language-impaired groups. However, only parameters related to the left uncinate, inferior fronto-occipital, and arcuate fasciculi were independently associated with the clinical phenotype.


CONCLUSIONS
Scalar metrics derived from the left uncinate, inferior fronto-occipital, and arcuate fasciculi were independently associated with language function. These results support the importance of these pathways in human language function in patients with MCDs.
Department of Radiology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
Michael J
MJ
Paldino
Department of Radiology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
Kara
K
Hedges
Outcomes and Impact Service, Texas Children's Hospital, Houston, TX 77030, USA.
Wei
W
Zhang
D000293:Adolescent; D001185:Artificial Intelligence; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D056324:Diffusion Tensor Imaging; D004827:Epilepsy / Q000150:complications / Q000473:pathology*; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging; D054220:Malformations of Cortical Development / Q000150:complications / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology; D012189:Retrospective Studies; D066127:White Matter / Q000473:pathology*
AF, arcuate fasciculus; Arcuate fasciculus; BA, Broca's area; Connectivity; DTI, diffusion tensor imaging; DWI, diffusion-weighted imaging; Epilepsy; FA, fractional anisotropy; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; Inferior fronto-occipital fasciculus; Language; MCDs, malformations of cortical development; MD, mean diffusivity; Malformations of cortical development; Tractography; UF, uncinate fasciculus; Uncinate fasciculus; WA, Wernicke's area