Abnormal Modular Organization of Functional Networks in Cognitively Impaired Children with Frontal Lobe Epilepsy

Abstract

Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.

Abnormal Functional Network Connectivity among Resting-State Networks in Children with Frontal Lobe Epilepsy

“…There was a weak association between connectivity in the right superior frontal gyrus of the frontal network and executive function and a significant association between connectivity in the right paracentral lobule of sensorimotor network and fine motor function. Vaessen et al 18 also found that higher modularity scores on resting-state fMRI were associated with decreased cognitive performance, as measured by increased computerized visual searching task reaction time. These findings suggest that impaired functional networks may be part of the neural underpinning for neuropsychological impairment.…”

“…The greater number of pair-wise ICs for the DMNattention and DMN-auditory networks in our study could be for the same reason. Vaessen et al 18 evaluated the resting-state connectivity by use of graph theoretical metrics of whole-brain networks. They found that children with FLE have a decrease in longrange and an increase in interhemispheric connectivity, as well as higher modularity scores, suggesting the presence of more functionally isolated brain modules.…”

“…There is currently limited information available on functional connectivity in children with epilepsy. 17,18 Frontal lobe epilepsy (FLE) is a common localization-related epilepsy in childhood. 19 The interictal discharges arising from a unilateral frontal lobe focus in FLE are more likely to spread to both hemispheres and form secondary bilateral synchrony, and children with FLE are also more likely to have secondarily generalized tonic-clonic seizures relative to TLE.…”

Frontal Lobe Epilepsy Alters Functional Connections Within the Brain's Motor Network: A Resting-State fMRI Study

“…This suggests that behavioral deficits in epilepsy may be the result of disrupted activity within associated resting-state networks, due to repeated seizure activity. A previous fMRI study reported that children with FLE had an increased number of functional connections within the frontal lobe, but a decreased number of functional connections between the frontal lobe and the rest of the brain (Vaessen et al, 2012). Furthermore, the extent of this frontal lobe isolation was positively correlated with the degree of cognitive impairment.…”

Evaluation and calibration of functional network modeling methods based on known anatomical connections

“…If the way the two regions vary is related, then they are said to be correlated. Correlati using fMRI data are plentiful and have looked at many things from the modular organization of functional networks in children with frontal lobe epilepsy (Vaessen et al, 2012), to language networks in subjects with anophthalmia (Watkins et al, 2012), to the reliability of the identification of the default mode network (Long et al, 2008). Partial correlation is also a widely used method which seeks to identify direct connections, rather than the direct and the indirect as identified with correlation , by regressing out information from all additional regions in the network in considering the relationship between two regions.…”