Brain functional connectivity changes 7 years after Neonatal Arterial Ischemic Stroke (NAIS): A resting state fMRI study

Abstract

Objective: Resting state fMRI (rs-fMRI) enables to study brain functional connectivity, i.e. the intrinsic functional architecture of brain networks at rest. NAIS is an exquisite model to study long-term plasticity after early focal lesions. We studied brain functional connectivity with rs-fMRI in school-age children after NAIS, focusing on language networks. Methods: From 100 newborns with NAIS followed until age 7 (n= 72, 2/3 boys, 85% MCA territory, 30% unilateral Cerebral Palsy, 49 % of atypical language profiles at N- EEL battery, without differences between left/right lesions, and with good global language performance), 38 patients and 29 age-matched controls underwent 3T rs- fMRI (exploitable in 32/26). After extended data preprocessing, we computed correlations (reflecting both direct and indirect connectivity) and partial correlations (direct connectivity only) within matrices of 64 bilateral homotopic regions grouped into 10 functional networks (the reference rs-fMRI functional atlas was derived from the controls data). Right lesions were flipped to the left side for group comparisons. Individual ROI volumes accounted for brain lesions, and statistics were corrected for multiple comparisons, FDR, p<0.05. Results: With both correlation and partial correlation, we found mostly reduced inter- hemispheric connectivity in the patient group as compared with controls (in motor, language and attentional networks). When restricting analysis to the language network, the reduction was strongest between homotopic inferior frontal and superior temporal regions (‘broca’ and ‘wernicke’). In the contralesional hemisphere, only intra- hemispheric correlations were increased mostly in the language network with stronger connections with the basal ganglia and motor network and within the visual occipital network. No connectivity difference could be evidenced between patients with either typical or atypical language. Conclusion: Rs-fMRI is useful to study the maturation of functional connectivity after NAIS, showing widespread reduction of inter-hemispheric connectivity and increased contralesional connectivity within the language network. The clinical correlates of this complex pattern remain to be fully understood.