Abstracts

Rationale:
Epilepsy patients hold risk for language decline following surgery that is not fully predicted by current tools. Resting-state functional connectivity (FC) may provide insights by quantifying the strength of ipsilateral connections to the language network referred to as “integration” and contralateral connections referred to as “segregation.” We examined FC in normal development and in epilepsy populations.  We expected left hemispheric integration to strengthen over childhood reflecting increased cohesion of language, and segregation to increase reflecting suppression of homologues; we expected these processes to be perturbed by epilepsy.
Method:
100 typically developing children & young adults (TD) (M=16yrs; Range 7-22) & 32 patients with focal epilepsy (M=13yrs, Range 7-20; 69% left; 34% frontal, 34% temporal) completed resting state 3T fMRI. Data was preprocessed & denoised using aCompCor in CONN toolbox. FC was computed for each vertex of grey matter in the target mask (frontal & temporal language regions) by calculating the strength of ipsilateral (integration) & contralateral connections (segregation), respectively, which were then used to compute an FC laterality index (FCLI; ((L-R)/(L+R)). Pearson correlations, linear & nonlinear multiple regression examined relationships between age & FCLI. ANOVAs compared FCLI between groups.
Results:
FCLI varied across TD with age & FCLI fitting a more complicated trajectory than a linear increase with age (integration age2 r=-.22, age3=.21, segregation age2 r=.10, age3 r=-.26; Figure 1). A cubic model of age best characterized frontal integration (F=3.01 p=.03 r2=.09 age3 p=.05) & segregation (F=4.15, p< .01  r2=.12, age3 p< .01). In patients, there was no relationship between age & frontal integration (p >.05, r= .04; age2 r=-.03; age3 r=-.07); trends were found for segregation (p=.06 r=-.34; age2 r=.26; age3 r=-.34; Figure 1). Regressions were not significant, likely due to small sample size. Temporal FCLI findings were not significant in either group. Frontal integration & segregation indicated stronger left-hemisphere network cohesion for TDs when compared to patients (Table 1), and temporal segregation indicated weaker right hemisphere suppression in patients. Group differences were significant after controlling for age.
Conclusion:
FC of frontal regions have protracted, nonlinear development by being more left-hemispheric into adolescence, followed by a return to network connections being equal between hemispheres in early adulthood. The epilepsy group showed little FCLI differences with age as FC connections remained equal between hemispheres. Our results suggest the normal developmental process of language connectivity is perturbed by epilepsy. The lack of lateralized integration and weaker temporal segregation in the epilepsy patients may represent compensatory contralateral engagement particularly in a largely left focus patient group. FC appears sensitive to brain maturation within the language network and may be a useful metric for improving the prediction of post-surgical language outcomes.
Funding:
:Hess Foundation