Mapping the landscape of cognitive development in children with epilepsy

ObjectiveNormal childhood development is defined by age-dependent improvement across cognitive abilities, including language, memory, psychomotor speed and executive function. Epilepsy is often associated with a global disruption in cognitive development, however, it is still largely unknown how epilepsy affects the overall organization of overlapping cognitive domains. The aim of the study was to evaluate how childhood epilepsy affects the developmental interrelationships between cognitive domains.MethodsWe performed a comprehensive assessment of neuropsychological function in 127 children with new onset epilepsy and 80 typically developing children matched for age, gender, and socio-demographic status. A cross-correlation matrix between the performances across multiple cognitive tests was used to assess the interrelationship between cognitive modalities for each group (patients and controls). A weighted network composed by the cognitive domains as nodes, and pair-wise domain correlation as links, was assessed using graph theory analyses, with focus on global network structure, network hubs and community structure.ResultsNormally developing children exhibited a cognitive network with well-defined modules, with verbal intelligence, reading and spelling skills occupying a central position in the developing network. Conversely, children with epilepsy demonstrated a less well-organized network with less clear separation between modules, and relative isolation of measures of attention and executive function.ConclusionOur findings demonstrate that childhood-onset epilepsy, even within its early course, is associated with an extensive disruption of cognitive neurodevelopmental organization. The approach used in this study may be useful to assess the effectiveness of future interventions aimed at mitigating the cognitive consequences of epilepsy

Shifted neuronal balance during stimulus-response integration in schizophrenia: an fMRI study

Schizophrenia is characterized by marked deficits in executive and psychomotor functions, as demonstrated for goal-directed actions in the antisaccade task. Recent studies, however, suggest that this deficit represents only one manifestation of a general deficit in stimulus–response integration and volitional initiation of motor responses. We here used functional magnetic resonance imaging to investigate brain activation patterns during a manual stimulus–response compatibility task in 18 schizophrenic patients and 18 controls. We found that across groups incongruent vs. congruent responses recruited a bilateral network consisting of dorsal fronto-parietal circuits as well as bilateral anterior insula, dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (preSMA). When testing for the main-effect across all conditions, patients showed significantly lower activation of the right DLPFC and, in turn, increased activation in a left hemispheric network including parietal and premotor areas as well as the preSMA. For incongruent responses patients showed significantly increased activation in a similar left hemispheric network, as well as additional activation in parietal and premotor regions in the right hemisphere. The present study reveals that hypoactivity in the right DLPFC in schizophrenic patients is accompanied by hyperactivity in several fronto-parietal regions associated with task execution. Impaired top-down control due to a dysfunctional DLPFC might thus be partly compensated by an up-regulation of task-relevant regions in schizophrenic patient

Graph theory and cognition: A complementary avenue for examining neuropsychological status in epilepsy

The recent revision of the classification of the epilepsies released by the ILAE Commission on Classification and Terminology (2005-2009) has been a major development in the field. Papers in this section of the special issue explore the relevance of other techniques to examine, categorize, and classify cognitive and behavioral comorbidities in epilepsy. In this review, we investigate the applicability of graph theory to understand the impact of epilepsy on cognition compared with controls and, then, the patterns of cognitive development in normally developing children which would set the stage for prospective comparisons of children with epilepsy and controls. The overall goal is to examine the potential utility of this analytic tool and approach to conceptualize the cognitive comorbidities in epilepsy. Given that the major cognitive domains representing cognitive function are interdependent, the associations between neuropsychological abilities underlying these domains can be referred to as a cognitive network. Therefore, the architecture of this cognitive network can be quantified and assessed using graph theory methods, rendering a novel approach to the characterization of cognitive status. We first provide fundamental information about graph theory procedures, followed by application of these techniques to cross-sectional analysis of neuropsychological data in children with epilepsy compared with that of controls, concluding with prospective analysis of neuropsychological development in younger and older healthy controls. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy"

Mapping the neuropsychological profile of temporal lobe epilepsy using cognitive network topology and graph theory

ObjectiveNormal cognitive function is defined by harmonious interaction among multiple neuropsychological domains. Epilepsy has a disruptive effect on cognition, but how diverse cognitive abilities differentially interact with one another compared with healthy controls (HC) is unclear. This study used graph theory to analyze the community structure of cognitive networks in adults with temporal lobe epilepsy (TLE) compared with that in HC.MethodsNeuropsychological assessment was performed in 100 patients with TLE and 82 HC. For each group, an adjacency matrix was constructed representing pair-wise correlation coefficients between raw scores obtained in each possible test combination. For each cognitive network, each node corresponded to a cognitive test; each link corresponded to the correlation coefficient between tests. Global network structure, community structure, and node-wise graph theory properties were qualitatively assessed.ResultsThe community structure in patients with TLE was composed of fewer, larger, more mixed modules, characterizing three main modules representing close relationships between the following: 1) aspects of executive function (EF), verbal and visual memory, 2) speed and fluency, and 3) speed, EF, perception, language, intelligence, and nonverbal memory. Conversely, controls exhibited a relative division between cognitive functions, segregating into more numerous, smaller modules consisting of the following: 1) verbal memory, 2) language, perception, and intelligence, 3) speed and fluency, and 4) visual memory and EF. Overall node-wise clustering coefficient and efficiency were increased in TLE.SignificanceAdults with TLE demonstrate a less clear and poorly structured segregation between multiple cognitive domains. This panorama suggests a higher degree of interdependency across multiple cognitive domains in TLE, possibly indicating compensatory mechanisms to overcome functional impairments

Prediction of Specific Depressive Symptom Clusters in Youth With Epilepsy: The NDDI-E-Y Versus Neuro-QOL SF

Objective: Proper assessment and early identification of depressive symptoms are essential to initiate treatment and minimize the risk for poor outcomes in youth with epilepsy (YWE). The current study examined the predictive utility of the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y) and the Neuro-QOL Depression Short Form (Neuro-QOL SF) in explaining variance in overall depressive symptoms and specific symptom clusters on the gold standard Children\u27s Depression Inventory-2 (CDI-2). Methods: Cross-sectional study examining 99 YWE (female 68, mean age 14.7 years) during a routine epilepsy visit, who completed self-report measures of depressive symptoms, including the NDDI-E-Y, CDI-2, and the Neuro-QOL SF. Caregivers completed a measure of seizure severity. All sociodemographic and medical information was evaluated through electronic medical record review. Results: After accounting for seizure and demographic variables, the NDDI-E-Y accounted for 45% of the variance in the CDI-2 Total score and the CDI-2 Ineffectiveness subscale. Furthermore, the NDDI-E-Y predicted CDI-2 Total scores and subscales similarly, with the exception of explaining significantly more variance in the CDI-2 Ineffectiveness subscale compared to the Negative Mood subscale. The NDDI-E-Y explained greater variance compared to Neuro-QOL SF across the Total (48% vs. 37%) and all CDI-2 subscale scores; however, the NDDI-E-Y emerged as a stronger predictor of only CDI-2 Ineffectiveness. Both the NDDI-E-Y and Neuro-QOL SF accounted for the lowest amount of variance in CDI-2 Negative Mood. Sensitivity was poor for the Neuro-QOL SF in predicting high versus low CDI-2 scores. Significance: The NDDI-E-Y has strong psychometrics and can be easily integrated into routine epilepsy care for quick, brief screening of depressive symptoms in YWE

Determining Patient Needs: A Partnership With South Carolina Advocates for Epilepsy (SAFE)

Purpose: The purpose of this study was to collaborate with a community partner to administer a current needs assessment of persons with epilepsy (PWE) and determine the types of resources that PWE would like to access through the community partner. Methods: A self-report needs assessment survey was administered to caregivers and PWE across the state of South Carolina during a community partner educational workshop (n= 20) and via secure software distributed through an email link (n= 54). Key findings: The most frequently reported challenges (\u3e. 50%) were concerns about finding time to participate in epilepsy community activities, the personal safety of the PWE, finding social connections or social support, finding mental or behavioral health services, and work concerns. However, top ranked concerns centered on personal safety (27.8%), lack of insurance/not enough money to pay for epilepsy treatment (15.3%), and difficulty with daily management of epilepsy (13.9%). Participants reported likely engagement with the epilepsy community partner via in-person meetings, over the phone, and through social media contacts; however, there were differences between PWE and caregivers regarding preferences for communication. Almost 60% endorsed that they would likely participate in a brief program to learn skills to manage their epilepsy daily. Significance: Persons with epilepsy in South Carolina continue to have many unmet needs and would access resources, if available, from a state-wide epilepsy community partner via various modes of communication