Disrupted Global and Regional Structural Networks and Subnetworks in Children with Localization-Related Epilepsy

Widjaja, Elysa; Zamyadi, Mojdeh; Raybaud, C; Snead, O. Carter; Doesburg, Sam M.; Smith, Mary Lou

doi:10.3174/ajnr.a4265

Cited by 40 publications

(18 citation statements)

References 34 publications

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“…Other investigators have also found particularly pronounced global connectivity disturbances in pediatric patients with frontal lobe epilepsy. Widjaja et al performed DTI analysis in children with nonlesional frontal lobe epilepsy, observing reduced structural connectivity in patients versus controls reflected by diminished network strength, clustering coefficient, path length, and global efficiency. This global network dysfunction may be related to widespread thinning of the neocortex also noted in this patient population .…”

Section: Global Connectivity Alterationsmentioning

confidence: 99%

Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings

2016

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Epilepsy is among the most common brain network disorders, and it is associated with substantial morbidity and increased mortality. While focal epilepsy was traditionally thought of as a regional brain disorder, growing evidence has demonstrated widespread network alterations in this disorder which extend beyond the epileptogenic zone from which seizures originate. The goal of this review is to summarize recent investigations examining functional and structural connectivity alterations in focal epilepsy, including neuroimaging and electrophysiology studies utilizing model-based or data-driven analysis methods. A significant subset of studies in both mesial temporal lobe epilepsy and focal neocortical epilepsy have demonstrated patterns of increased connectivity related to the epileptogenic zone, coupled with decreased connectivity in widespread distal networks. Connectivity patterns appear to be related to the duration and severity of disease, suggesting progressive connectivity reorganization in the setting of recurrent seizures over time. Global resting-state connectivity disturbances in focal epilepsy have been linked to neurocognitive problems, including memory and language disturbances. While it is possible that increased connectivity in a particular brain region may enhance the propensity for seizure generation, it is not clear if global reductions in connectivity represent the damaging consequences of recurrent seizures, or an adaptive mechanism to prevent seizure propagation away from the epileptogenic zone. Overall, studying the connectome in focal epilepsy is a critical endeavor which may lead to improved strategies for epileptogenic zone localization, surgical outcome prediction, and a better understanding of the neuropsychological implications of recurrent seizures.

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Section: Global Connectivity Alterationsmentioning

confidence: 99%

Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings

2016

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“…Studies using diffusion-weighted imaging have identified 'disconnection syndromes' in schizophrenia (Stephan et al, 2009;Zalesky et al, 2011), depression (Bai et al, 2012), attention-deficit hyperactivity disorder (Cao et al, 2013), and epilepsy (Widjaja et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk

Jeganathan

Perry

Bassett

et al. 2017

Preprint

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Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocircuitry that underlie cognitive-emotional control in bipolar disorder (BD) and in unaffected siblings or children at high genetic risk (HR). It has been difficult to quantify the mechanism by which structural changes disrupt the superimposed brain dynamics, leading to the emotional lability that is characteristic of BD. Average controllability is a concept from network control theory that extends structural connectivity data to estimate the manner in which local neuronal fluctuations spread from a node or subnetwork to alter the state of the rest of the brain. We used this theory to ask whether structural connectivity deficits previously observed in HR (n=84, mean age 22.4) individuals, patients with BD (n=38, mean age 23.9), and age-and gender-matched controls (n=96, mean age 22.6) translate to differences in the ability of brain systems to be manipulated between states. Localized impairments in network controllability were seen in the left parahippocampal, left middle occipital, left superior frontal, right inferior frontal, and right precentral gyri in BD and HR groups. Subjects with BD had distributed deficits in a subnetwork containing the left superior and inferior frontal gyri, postcentral gyrus, and insula (p=0.004). HR participants had controllability deficits in a right-lateralized subnetwork involving connections between the dorsomedial and ventrolateral prefrontal cortex, the superior temporal pole, putamen, and caudate nucleus (p=0.008). Between-group controllability differences were attenuated after removal of topological factors by network randomization. Some previously reported differences in network connectivity were not associated with controllability-differences, likely reflecting the contribution of more complex brain network properties. These analyses highlight the potential functional consequences of altered brain networks in BD, and may guide future clinical interventions. Highlights• Control theory estimates how neuronal fluctuations spread from local networks.• We compare brain controllability in bipolar disorder and their high-risk relatives.• These groups have impaired controllability in networks supporting cognitive and emotional control. • Weaker connectivity as well as topological alterations contribute to these changes. AbbreviationsCN = control; HR = high-risk; BD = bipolar disorder; MRI = magnetic resonance imaging; fMRI = functional MRI; dMRI = diffusion MRI.4

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“…Here the focus of interest has been the impact of epilepsy and its treatment on brain development and understanding the relationship of abnormalities in brain structure with commonly occurring cognitive, academic, and behavioral comorbidities (Besseling et al, 2014; Bonilha et al, 2014; Braakman et al, 2014, 2015; Ibrahim et al, 2014; Widjaja et al, 2014a; Widjaja et al, 2015; Widjaja et al, 2014b). …”

Section: Introductionmentioning

confidence: 99%

Brain structure and organization five decades after childhood onset epilepsy

Garcia‐Ramos¹,

Bobholz²,

Dabbs³

et al. 2017

Human Brain Mapping

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The purpose of this project was to characterize brain structure and organization in persons with active and remitted childhood onset epilepsy 50 years after diagnosis compared to healthy controls. Participants from a population-based investigation of uncomplicated childhood onset epilepsy were followed up 5 decades later. Forty-one participants had a history of childhood onset epilepsy (mean age of onset= 5.2 yrs, current chronological age= 56.0 yrs) and were compared to 48 population-based controls (mean age= 55.9 yrs). Of the epilepsy participants, 8 had persisting active epilepsy and in 33 the epilepsy had remitted. All participants underwent 3T MRI with subsequent vertex analysis of cortical volume, thickness, surface area and gyral complexity. In addition, cortical and subcortical volumes, including regions of the frontal, parietal, temporal, and occipital lobes, and subcortical structures including amygdala, thalamus, and hippocampus, were analyzed using graph theory techniques. There were modest group differences in traditional vertex-based analyses of cortical volume, thickness, surface area and gyral index, as well as across volumes of subcortical structures, after correction for multiple comparisons. Graph theory analyses revealed suboptimal topological structural organization with enhanced network segregation and reduced global integration in the epilepsy participants compared to controls, these patterns significantly more extreme in the active epilepsy group. Furthermore, both groups with epilepsy presented a greater number of higher Z-score regions in betweenness centrality (BC) than lower Z-score regions compared to controls. Also, contrary to the group with remitted epilepsy, patients with active epilepsy presented most of their high BC Z-score regions in subcortical areas including the amygdala, thalamus, hippocampus, pallidum and accumbens. Overall, this population-based investigation of long term outcome (5 decades) of childhood onset epilepsy reveals persisting abnormalities, especially when examined by graph theoretical measurements, and provides new insights into the very long term outcomes of active and remitted epilepsy.

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Disrupted Global and Regional Structural Networks and Subnetworks in Children with Localization-Related Epilepsy

Cited by 40 publications

References 34 publications

Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings

Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings

Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk

Brain structure and organization five decades after childhood onset epilepsy

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