Brain Network Organization in Focal Epilepsy: A Systematic Review and Meta-Analysis.

Normal brain functioning is presumed to depend upon interacting regions within large-scale neuronal networks. Increasing evidence exists that interictal network alterations in focal epilepsy are associated with cognitive and behavioral deficits. Nevertheless, the reported network alterations are inconclusive and prone to low statistical power due to small sample sizes as well as modest effect sizes. We therefore systematically reviewed the existing literature and conducted a meta-analysis to characterize the changes in whole-brain interictal focal epilepsy networks at sufficient power levels. We focused on the two most commonly used metrics in whole-brain networks: average path length and average clustering coefficient. Twelve studies were included that reported whole-brain network average path length and average clustering coefficient characteristics in patients and controls. The overall group difference, quantified as the standardized mean average path length difference between epilepsy and control groups, corresponded to a significantly increased average path length of 0.29 (95% confidence interval (CI): 0.12 to 0.45, p = 0.0007) in the epilepsy group. This suggests a less integrated interictal whole-brain network. Similarly, a significantly increased standardized mean average clustering coefficient of 0.35 (CI: 0.05 to 0.65, p = 0.02) was found in the epilepsy group in comparison with controls, pointing towards a more segregated interictal network. Sub-analyses revealed similar results for functional and structural networks in terms of effect size and directionality for both metrics. In addition, we found individual network studies to be prone to low power due to the relatively small group differences in average path length and average clustering coefficient in combination with small sample sizes. The pooled network characteristics support the hypothesis that focal epilepsy has widespread detrimental effects, that is, reduced integration and increased segregation, on whole brain interictal network organization, which may relate to the co-morbid cognitive and behavioral impairments often reported in patients with focal epilepsy.