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

van Diessen E, Zweiphenning WJ, Jansen FE, Stam CJ, Braun KP, Otte WM - PLoS ONE (2014)

Bottom Line: Nevertheless, the reported network alterations are inconclusive and prone to low statistical power due to small sample sizes as well as modest effect sizes.Sub-analyses revealed similar results for functional and structural networks in terms of effect size and directionality for both metrics.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Meta-analysis of the average clustering coefficient separated by network modality.The forest plot displays the standardized mean differences (SMD) between focal epilepsy patients and controls with the 95% confidence intervals (CI) for the functional and structural network studies reporting the average clustering coefficient. No difference between patients and controls is specified with a vertical line at 0. The overall pooled SMD for the functional average clustering coefficient was 0.20 (CI: −0.14, 0.55, p = 0.25) and 0.64 for the structural average clustering coefficient (CI: 0.09 to 1.18, p = 0.02). The SMDs of these subgroups were not statistically different (p = 0.18, I2 = 43.2%).
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pone-0114606-g006: Meta-analysis of the average clustering coefficient separated by network modality.The forest plot displays the standardized mean differences (SMD) between focal epilepsy patients and controls with the 95% confidence intervals (CI) for the functional and structural network studies reporting the average clustering coefficient. No difference between patients and controls is specified with a vertical line at 0. The overall pooled SMD for the functional average clustering coefficient was 0.20 (CI: −0.14, 0.55, p = 0.25) and 0.64 for the structural average clustering coefficient (CI: 0.09 to 1.18, p = 0.02). The SMDs of these subgroups were not statistically different (p = 0.18, I2 = 43.2%).

Mentions: Modality specific summary estimates for the average path length and average clustering coefficient are provided in Fig. 5 and 6, respectively. Both functional and structural focal epilepsy networks were characterized by a significantly increased average path length as compared to control networks: 0.26 for the functional (CI: 0.05 to 0.47, p = 0.02) and 0.30 for the structural networks (CI: 0.01 to 0.60, p = 0.04) (Fig. 5). The average clustering coefficient was significantly increased in structural focal epilepsy networks: 0.64 (CI: 0.09 to 1.18, p = 0.02). There was no significant difference in average clustering coefficient for the functional epilepsy networks: 0.20 (CI: −0.14, 0.55, p = 0.25) (Fig. 6). Age group specific estimates revealed an increased average path length and average clustering coefficient only for the adults with epilepsy in comparison with controls (see S3a Figure and S3b Figure in S1 File). No difference in average path length (p = 0.18) and average clustering coefficient (p = 0.13) was found between adults and children with epilepsy. Specific estimates for the subgroup analysis for different types of epilepsy revealed an increased average path length and clustering coefficient for the temporal lobe epilepsy patients only in comparison with controls. There was no difference between the temporal lobe, extratemporal and brain tumor groups in terms of average path length (p = 0.48). The standardized mean differences were significantly different for the average clustering coefficient (p = 0.0002) with an evidently increased segregation for the temporal lobe epilepsy subgroup, but due to a considerable heterogeneity (I2 = 88.1%), not reliable (see S4a Figure and S4b Figure in S1 File).


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

van Diessen E, Zweiphenning WJ, Jansen FE, Stam CJ, Braun KP, Otte WM - PLoS ONE (2014)

Meta-analysis of the average clustering coefficient separated by network modality.The forest plot displays the standardized mean differences (SMD) between focal epilepsy patients and controls with the 95% confidence intervals (CI) for the functional and structural network studies reporting the average clustering coefficient. No difference between patients and controls is specified with a vertical line at 0. The overall pooled SMD for the functional average clustering coefficient was 0.20 (CI: −0.14, 0.55, p = 0.25) and 0.64 for the structural average clustering coefficient (CI: 0.09 to 1.18, p = 0.02). The SMDs of these subgroups were not statistically different (p = 0.18, I2 = 43.2%).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4262431&req=5

pone-0114606-g006: Meta-analysis of the average clustering coefficient separated by network modality.The forest plot displays the standardized mean differences (SMD) between focal epilepsy patients and controls with the 95% confidence intervals (CI) for the functional and structural network studies reporting the average clustering coefficient. No difference between patients and controls is specified with a vertical line at 0. The overall pooled SMD for the functional average clustering coefficient was 0.20 (CI: −0.14, 0.55, p = 0.25) and 0.64 for the structural average clustering coefficient (CI: 0.09 to 1.18, p = 0.02). The SMDs of these subgroups were not statistically different (p = 0.18, I2 = 43.2%).
Mentions: Modality specific summary estimates for the average path length and average clustering coefficient are provided in Fig. 5 and 6, respectively. Both functional and structural focal epilepsy networks were characterized by a significantly increased average path length as compared to control networks: 0.26 for the functional (CI: 0.05 to 0.47, p = 0.02) and 0.30 for the structural networks (CI: 0.01 to 0.60, p = 0.04) (Fig. 5). The average clustering coefficient was significantly increased in structural focal epilepsy networks: 0.64 (CI: 0.09 to 1.18, p = 0.02). There was no significant difference in average clustering coefficient for the functional epilepsy networks: 0.20 (CI: −0.14, 0.55, p = 0.25) (Fig. 6). Age group specific estimates revealed an increased average path length and average clustering coefficient only for the adults with epilepsy in comparison with controls (see S3a Figure and S3b Figure in S1 File). No difference in average path length (p = 0.18) and average clustering coefficient (p = 0.13) was found between adults and children with epilepsy. Specific estimates for the subgroup analysis for different types of epilepsy revealed an increased average path length and clustering coefficient for the temporal lobe epilepsy patients only in comparison with controls. There was no difference between the temporal lobe, extratemporal and brain tumor groups in terms of average path length (p = 0.48). The standardized mean differences were significantly different for the average clustering coefficient (p = 0.0002) with an evidently increased segregation for the temporal lobe epilepsy subgroup, but due to a considerable heterogeneity (I2 = 88.1%), not reliable (see S4a Figure and S4b Figure in S1 File).

Bottom Line: Nevertheless, the reported network alterations are inconclusive and prone to low statistical power due to small sample sizes as well as modest effect sizes.Sub-analyses revealed similar results for functional and structural networks in terms of effect size and directionality for both metrics.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus