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The relationship between temporal lobe epilepsy and psychopathology has had a long and contentious history with diverse views regarding the presence, nature and severity of emotional–behavioural problems in this patient population. To address these controversies, we take a new person-centred approach through the application of unsupervised machine learning techniques to identify underlying latent groups or behavioural phenotypes. Addressed are the distinct psychopathological profiles, their linked frequency, patterns and severity and the disruptions in morphological and network properties that underlie the identified latent groups. A total of 114 patients and 83 controls from the Epilepsy Connectome Project were administered the Achenbach System of Empirically Based Assessment inventory from which six Diagnostic and Statistical Manual of Mental Disorders-oriented scales were analysed by unsupervised machine learning analytics to identify latent patient groups. Identified clusters were contrasted to controls as well as to each other in order to characterize their association with sociodemographic, clinical epilepsy and morphological and functional imaging network features. The concurrent validity of the behavioural phenotypes was examined through other measures of behaviour and quality of life. Patients overall exhibited significantly higher (abnormal) scores compared with controls. However, cluster analysis identified three latent groups: (i) unaffected, with no scale elevations compared with controls (Cluster 1, 37%); (ii) mild symptomatology characterized by significant elevations across several Diagnostic and Statistical Manual of Mental Disorders-oriented scales compared with controls (Cluster 2, 42%); and (iii) severe symptomatology with significant elevations across all scales compared with controls and the other temporal lobe epilepsy behaviour phenotype groups (Cluster 3, 21%). Concurrent validity of the behavioural phenotype grouping was demonstrated through identical stepwise links to abnormalities on independent measures including the National Institutes of Health Toolbox Emotion Battery and quality of life metrics. There were significant associations between cluster membership and sociodemographic (handedness and education), cognition (processing speed), clinical epilepsy (presence and lifetime number of tonic–clonic seizures) and neuroimaging characteristics (cortical volume and thickness and global graph theory metrics of morphology and resting-state functional MRI). Increasingly dispersed volumetric abnormalities and widespread disruptions in underlying network properties were associated with the most abnormal behavioural phenotype. Psychopathology in these patients is characterized by a series of discrete latent groups that harbour accompanying sociodemographic, clinical and neuroimaging correlates. The underlying neurobiological patterns suggest that the degree of psychopathology is linked to increasingly dispersed abnormal brain networks. Similar to cognition, machine learning approaches support a novel developing taxonomy of the comorbidities of epilepsy.

Resting state functional MRI (R-fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease-related variability in intrinsic connectivity networks may influence our interpretation of R-fMRI data.MethodsWe used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R-fMRI differences between Parkinson’s disease (PD) patients who showed cognitive decline, those who remained cognitively stable, and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both Network-based Statistics (NBS) and calculations of mean inter- and intra-network connectivity within pre-defined functional networks.ResultsThe NBS analysis showed that PD participants who remained cognitively stable showed exclusively (at baseline) or predominantly (at follow-up) increased intra-network connectivity, whereas decliners showed exclusively reduced intra-network and inter-(ventral attention and default mode) connectivity, in comparison to the control group. Evaluation of mean connectivity between all ROIs within a priori networks showed that decliners had consistently reduced inter-network connectivity for ventral attention, somatomotor, visual, and striatal networks, and reduced intra-network connectivity for ventral attention network to striatum and cerebellum.ConclusionsThese findings suggest that specific functional connectivity covariance patterns differentiate PD cognitive subtypes and may predict cognitive decline. Further, increased intra and internetwork synchrony may support cognitive function in the face of PD-related network disruptions.Key PointsResting state functional MRI (R-fMRI) can be used to probe changes in brain networks related to disease. Personalized approaches can be used to address spatial variations in R-fMRI correlation maxima influenced by individual variation or brain plasticity in response to disease.Longitudinal R-fMRI from cognitively stable Parkinson’s patients were compared with those who experienced decline as well as controls using a personalized approach.Cognitively stable patients showed increased inter and intra-network synchrony while decliners showed decreases that may have preceded cognitive decline.

In Parkinson’s disease (PD), reduced cerebral cortical thickness may reflect network-based degeneration. This study performed cognitive assessment and brain MRI in 30 PD participants and 41 controls at baseline and 18 months later. We hypothesized that cerebral cortical thickness and volume, as well as change in these metrics, would differ between PD participants who remained cognitively stable and those who experienced cognitive decline. Dividing the participant sample into PD-stable, PD-decline, and control-stable groups, we compared mean cortical thickness and volume within segments that comprise the prefrontal cognitive-control, memory, dorsal spatial, and ventral object-based networks at baseline. We then compared the rate of change in cortical thickness and volume between the same groups using a vertex-wise approach. We found that the PD-decline group had lower cortical thickness within all 4 cognitive networks in comparison with controls, as well as lower cortical thickness within the prefrontal and medial temporal networks in comparison with the PD-stable group. The PD-decline group also experienced a greater rate of volume loss in the lateral temporal cortices in comparison with the control group. This study suggests that lower thickness and volume in prefrontal, medial, and lateral temporal regions may portend cognitive decline in PD.

Objective To identity phenotypes of self‐reported symptoms of psychopathology and their correlates in patients with temporal lobe epilepsy (TLE). Method 96 patients with TLE and 82 controls were administered the Symptom Checklist 90‐Revised (SCL‐90‐R) to characterize emotional‐behavioral status. The nine symptom scales of the SCL‐90‐R were analyzed by unsupervised machine learning techniques to identify latent TLE groups. Identified clusters were contrasted to controls to characterize their association with sociodemographic, clinical epilepsy, neuropsychological, psychiatric, and neuroimaging factors. Results TLE patients as a group exhibited significantly higher (abnormal) scores across all SCL‐90‐R scales compared to controls. However, cluster analysis identified three latent groups: (1) unimpaired with no scale elevations compared to controls (Cluster 1, 42% of TLE patients), (2) mild‐to‐moderate symptomatology characterized by significant elevations across several SCL‐90‐R scales compared to controls (Cluster 2, 35% of TLE patients), and (3) marked symptomatology with significant elevations across all scales compared to controls and the other TLE phenotype groups (Cluster 3, 23% of TLE patients). There were significant associations between cluster membership and demographic (education), clinical epilepsy (perceived seizure severity, bitemporal lobe seizure onset), and neuropsychological status (intelligence, memory, executive function), but with minimal structural neuroimaging correlates. Concurrent validity of the behavioral phenotype grouping was demonstrated through association with psychiatric (current and lifetime‐to‐date DSM IV Axis 1 disorders and current treatment) and quality‐of‐life variables. Significance Symptoms of psychopathology in patients with TLE are characterized by a series of discrete phenotypes with accompanying sociodemographic, cognitive, and clinical correlates. Similar to cognition in TLE, machine learning approaches suggest a developing taxonomy of the comorbidities of epilepsy.

Objective To characterize the presence and nature of discrete behavioral phenotypes and their correlates in a cohort of youth with new and recent onset focal and generalized epilepsies. Methods The parents of 290 youth (age = 8-18 years) with epilepsy (n = 183) and typically developing participants (n = 107) completed the Child Behavior Checklist for children aged 6-18 from the Achenbach System of Empirically Based Assessment. The eight behavior problem scales were subjected to hierarchical clustering analytics to identify behavioral subgroups. To characterize the external validity and co-occurring comorbidities of the identified subgroups, we examined demographic features (age, gender, handedness), cognition (language, perception, attention, executive function, speed), academic problems (present/absent), clinical epilepsy characteristics (epilepsy syndrome, medications), familial factors (parental intelligence quotient, education, employment), neuroimaging features (cortical thickness), parent-observed day-to-day executive function, and number of lifetime-to-date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses. Results Hierarchical clustering identified three behavioral phenotypes, which included no behavioral complications (Cluster 1, 67% of epilepsy cohort [n = 122]), nonexternalizing problems (Cluster 2, 11% of cohort [n = 21]), and combined internalizing and externalizing problems (Cluster 3, 22% of cohort [n = 40]). These behavioral phenotypes were characterized by orderly differences in personal characteristics, neuropsychological status, history of academic problems, parental status, cortical thickness, daily executive function, and number of lifetime-to-date DSM-IV diagnoses. Cluster 1 was most similar to controls across most metrics, whereas Cluster 3 was the most abnormal compared to controls. Epilepsy syndrome was not a predictor of cluster membership. Significance Youth with new and recent onset epilepsy fall into three distinct behavioral phenotypes associated with a variety of co-occurring features and comorbidities. This approach identifies important phenotypes of behavior problem presentations and their accompanying factors that serve to advance clinical and theoretical understanding of the behavioral complications of children with epilepsy and the complex conditions with which they co-occur.

Behavioral and personality disorders in temporal lobe epilepsy (TLE) have been a topic of interest and controversy for decades, with less attention paid to alterations in normal personality structure and traits. In this investigation, core personality traits (the Big 5) and their neurobiological correlates in TLE were explored using the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) and structural magnetic resonance imaging (MRI) through the Epilepsy Connectome Project (ECP). NEO-FFI scores from 67 individuals with TLE (34.6 ± 9.5 years; 67% women) were compared to 31 healthy controls (32.8 ± 8.9 years; 41% women) to assess differences in the Big 5 traits (agreeableness, openness, conscientiousness, neuroticism, and extraversion). Individuals with TLE showed significantly higher neuroticism, with no significant differences on the other traits. Neural correlates of neuroticism were then determined in participants with TLE including cortical and subcortical volumes. Distributed reductions in cortical gray matter volumes were associated with increased neuroticism. Subcortically, hippocampal and amygdala volumes were negatively associated with neuroticism. These results offer insight into alterations in the Big 5 personality traits in TLE and their brain-related correlates.

This study investigated the association between processing speed and cortical morphometry in children with idiopathic epilepsies (n = 81) versus healthy controls (n = 57), age 8-18. Participants underwent 1.5 T MRI scanning and cognitive testing including assessment of psychomotor speed (Digit Symbol) at or near the time of epilepsy diagnosis. Vertex analyses of cortical volume, thickness, surface area, and local gyrification index (LGI), as well as volume-based analyses of subcortical structures and cerebellum, were used to determine the morphometric correlates of Digit Symbol performance. Group comparisons revealed that the epilepsy and control groups exhibited different patterns of morphometric association with Digit Symbol performance - controls exhibited several areas of correlation between LGI and psychomotor speed, whereas participants with focal epilepsies exhibited different areas of correlation in different directions, and participants with generalized epilepsy exhibited no correlations. The other cortical morphometric measures showed no regions of significant correlation with Digit Symbol performance. In addition, cerebellum and brain stem volumes correlated with Digit Symbol performance in the control group, but not in epilepsy patients. These results suggest that LGI analysis is able to capture nuanced relationships between features of cortical and subcortical morphology with psychomotor speed, these relationships disrupted in different ways in children with epilepsy.

Purpose Psychomotor slowing is a common but understudied cognitive impairment in epilepsy. Here we test the hypothesis that psychomotor slowing is associated with alterations in brain status reflected through network analysis of large scale structural networks. We test the hypothesis that children with epilepsy with cognitive slowing at diagnosis will exhibit a cross-sectional and prospective pattern of altered brain development. Methods A total of 78 children (age 8–18) with new/recent idiopathic epilepsies underwent 1.5 T MRI with network analysis of cortical, subcortical and cerebellar volumes. Children with epilepsy were divided into slow and fast psychomotor speed groups (adjusted for age, intelligence and epilepsy syndrome). Results At baseline, slow-speed performers (SSP) presented lower modularity, lower global efficiency, higher transitivity, and lower number of hubs than fast-speed performers (FSP). Community structure in SSP exhibited poor association between cortical regions and both subcortical structures and the cerebellum while FSP presented well-defined communities. Prospectively, SSP displayed lower modularity but higher global efficiency and transitivity compared to FSP. Modules in FSP showed higher integration between and within themselves compared to SSP. SSP showed hubs mainly from frontal and temporal regions while in FSP were spread among frontal, temporal, parietal, subcortical areas and the left cerebellum. Implications Results suggest the presence of widespread alterations in large scale networks between fast- and slow-speed children with recent onset epilepsies both at baseline and 2 years later. Slower processing speed appears to be a marker of abnormal brain development antecedent to epilepsy onset as well as brain development over the 2 years following diagnosis., Highlights • Baseline: slow-speed performers (SSP) showed lower modularity and global efficiency • They also showed higher transitivity but fewer hubs than fast-speed performers (FSP) • Prospective: SSP showed lower modularity, harmonic mean and higher transitivity • Regional volume changes seem to be occurring as one in SSP, but more modular in FSP • SSP showed hubs mainly from frontal and temporal while FSP showed them widespread

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 with 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 years, current chronological age = 56.0 years) and were compared with 48 population-based controls (mean age = 55.9 years). 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 with 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 with 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. Hum Brain Mapp 38:3289-3299, 2017. © 2017 Wiley Periodicals, Inc.

ObjectiveBenign epilepsy with centrotemporal spikes (BECTS) is the most common childhood idiopathic localization-related epilepsy syndrome. BECTS presents normal routine magnetic resonance imaging (MRI); however, quantitative analytic techniques have captured subtle cortical and subcortical magnetic resonance anomalies. Network science, including graph theory (GT) analyses, facilitates understanding of brain covariance patterns, potentially informing in important ways how this common self-limiting epilepsy syndrome may impact normal patterns of brain and cognitive development.MethodsGT analyses examined the developmental covariance among cortical and subcortical regions in children with new/recent onset BECTS (n=19) and typically developing healthy controls (n=22) who underwent high-resolution MRI and cognitive assessment at baseline and 2years later. Global (transitivity, global efficiency, and modularity index [Q]) and regional measures (local efficiency and hubs) were investigated to characterize network development in each group. Associations between baseline-based GT measures and cognition at both time points addressed the implications of GT analyses for cognition and prospective cognitive development. Furthermore, an individual contribution measure was investigated, reflecting how important for cognition it is for BECTS to resemble the correlation matrices of controls.ResultsGroups exhibited similar Q and overall network configuration, with BECTS presenting significantly higher transitivity and both global and local efficiency. Furthermore, both groups presented a similar number of hubs, with BECTS showing a higher number in temporal lobe regions compared to controls. The investigated measures were negatively associated with 2-year cognitive outcomes in BECTS.SignificanceChildren with BECTS present a higher-than-normal global developmental configuration compared to controls, along with divergence from normality in terms of regional configuration. Baseline GT measures demonstrate potential as a cognitive biomarker to predict cognitive outcome in BECTS 2years after diagnosis. Similarities and differences in developmental network configurations and their implications for cognition and behavior across common epilepsy syndromes are of theoretical interest and clinical relevance.

Highlights • TLE patients have older brain ages both functionally and structurally. • Functional brain age is a better predictor of cognitive abilites in TLE patients. • Weaker bilateral frontal/temporal connections affect functional brain aging in TLE. • Functional age mediates some of chronological age-fluid cognition relationships. • Accelerated brain aging in TLE affected by both seizure burden and polytherapy., The association of epilepsy with structural brain changes and cognitive abnormalities in midlife has raised concern regarding the possibility of future accelerated brain and cognitive aging and increased risk of later life neurocognitive disorders. To address this issue we examined age-related processes in both structural and functional neuroimaging among individuals with temporal lobe epilepsy (TLE, N = 104) who were participants in the Epilepsy Connectome Project (ECP). Support vector regression (SVR) models were trained from 151 healthy controls and used to predict TLE patients’ brain ages. It was found that TLE patients on average have both older structural (+6.6 years) and functional (+8.3 years) brain ages compared to healthy controls. Accelerated functional brain age (functional – chronological age) was mildly correlated (corrected P = 0.07) with complex partial seizure frequency and the number of anti-epileptic drug intake. Functional brain age was a significant correlate of declining cognition (fluid abilities) and partially mediated chronological age-fluid cognition relationships. Chronological age was the only positive predictor of crystallized cognition. Accelerated aging is evident not only in the structural brains of patients with TLE, but also in their functional brains. Understanding the causes of accelerated brain aging in TLE will be clinically important in order to potentially prevent or mitigate their cognitive deficits.

Objective The objective of this study was to identify cognitive phenotypes in children with new-onset focal and generalized idiopathic epilepsies and determine their relationship with epilepsy syndrome, brain structure, neurodevelopmental history, and family characteristics. Methods One hundred thirty-eight children with new-onset epilepsy and 95 controls (age: 8–18) underwent neuropsychological, clinical, and quantitative MR evaluations. Control participants' neuropsychological data were subjected to confirmatory factor analysis and then resultant factor scores were applied to participants with epilepsy and subjected to latent class analysis. Identified cognitive phenotypes were examined in relation to epilepsy syndrome, quantitative neuroimaging, and familial and neurodevelopmental variables. Results Confirmatory factor analysis identified five cognitive factors (verbal, perceptual, speed, attention, executive), and latent class analysis identified three clusters of participants with epilepsy: 1) average and similar to controls, 2) mild impairment across multiple cognitive domains, and 3) impairment across all domains with severe attentional impairment, representing 44%, 44%, and 12% of the epilepsy sample, respectively. Cognitive phenotype membership was not associated with epilepsy syndrome but was associated with increasing abnormalities in brain structure, parental IQ, and features of early developmental history. Significance Cognitive phenotypes are present in idiopathic childhood epilepsies that are unassociated with traditional epilepsy syndromes but are associated with measures of brain structure, family history, and neurodevelopmental features.

Highlights • Cognitive impairment is a major comorbidity of temporal lobe epilepsy (TLE). • Three discrete cognitive phenotypes of TLE are identified here. • The phenotypes are linked to network, clinical, and socioeconomic characteristics. • This taxonomy advances clinical and theoretical understanding of the cognitive complications of TLE., This study explored the taxonomy of cognitive impairment within temporal lobe epilepsy and characterized the sociodemographic, clinical and neurobiological correlates of identified cognitive phenotypes. 111 temporal lobe epilepsy patients and 83 controls (mean ages 33 and 39, 57% and 61% female, respectively) from the Epilepsy Connectome Project underwent neuropsychological assessment, clinical interview, and high resolution 3T structural and resting-state functional MRI. A comprehensive neuropsychological test battery was reduced to core cognitive domains (language, memory, executive, visuospatial, motor speed) which were then subjected to cluster analysis. The resulting cognitive subgroups were compared in regard to sociodemographic and clinical epilepsy characteristics as well as variations in brain structure and functional connectivity. Three cognitive subgroups were identified (intact, language/memory/executive function impairment, generalized impairment) which differed significantly, in a systematic fashion, across multiple features. The generalized impairment group was characterized by an earlier age at medication initiation (P

Objective Structural and functional magnetic resonance imaging (MRI) studies have consistently documented cortical and subcortical abnormalities in patients with juvenile myoclonic epilepsy (JME). However, little is known about how these structural abnormalities emerge from the time of epilepsy onset and how network interactions between and within cortical and subcortical regions may diverge in youth with JME compared to typically developing children. Methods We examined prospective covariations of volumetric differences derived from high-resolution structural MRI during the first 2 years of epilepsy diagnosis in a group of youth with JME (n = 21) compared to healthy controls (n = 22). We indexed developmental brain changes using graph theory by computing network metrics based on the correlation of the cortical and subcortical structural covariance near the time of epilepsy and 2 years later. Results Over 2 years, normally developing children showed modular cortical development and network integration between cortical and subcortical regions. In contrast, children with JME developed a highly correlated and less modular cortical network, which was atypically dissociated from subcortical structures. Furthermore, the JME group also presented higher clustering and lower modularity indices than controls, indicating weaker modules or communities. The local efficiency in JME was higher than controls across the majority of cortical nodes. Regarding network hubs, controls presented a higher number than youth with JME that were spread across the brain with ample representation from the different modules. In contrast, children with JME showed a lower number of hubs that were mainly from one module and comprised mostly subcortical structures. Significance Youth with JME prospectively developed a network of highly correlated cortical regions dissociated from subcortical structures during the first 2 years after epilepsy onset. The cortical-subcortical network dissociation provides converging insights into the disparate literature of cortical and subcortical abnormalities found in previous studies.

Cognitive slowing is a known but comparatively under-investigated neuropsychological complication of the epilepsies in relation to other known cognitive comorbidities such as memory, executive function and language. Here we focus on a novel metric of processing speed, characterize its relative salience compared to other cognitive difficulties in epilepsy, and explore its underlying neurobiological correlates. Research participants included 55 patients with temporal lobe epilepsy (TLE) and 58 healthy controls from the Epilepsy Connectome Project (ECP) who were administered a battery of tests yielding 14 neuropsychological measures, including selected tests from the NIH Toolbox-Cognitive Battery, and underwent 3T MRI and resting state fMRI. TLE patients exhibited a pattern of generalized cognitive impairment with very few lateralized abnormalities. Using the neuropsychological measures, machine learning (Support Vector Machine binary classification model) classified the TLE and control groups with 74% accuracy with processing speed (NIH Toolbox Pattern Comparison Processing Speed Test) the best predictor. In TLE, slower processing speed was associated predominantly with decreased local gyrification in regions including the rostral and caudal middle frontal gyrus, inferior precentral cortex, insula, inferior parietal cortex (angular and supramarginal gyri), lateral occipital cortex, rostral anterior cingulate, and medial orbital frontal regions, as well as three small regions of the temporal lobe. Slower processing speed was also associated with decreased connectivity between the primary visual cortices in both hemispheres and the left supplementary motor area, as well as between the right parieto-occipital sulcus and right middle insular area. Overall, slowed processing speed is an important cognitive comorbidity of TLE associated with altered brain structure and connectivity.

Using a hypothesis-driven approach, subcortical and cortical regions implicated in anxiety disorders in the general population were examined in children with recent-onset epilepsy with versus without anxiety compared to controls. This study reports frequency of anxiety disorders while examining familial, clinical, and demographic variables associated with anxiety in children with epilepsy.Participants included 88 children with epilepsy aged 8-18 years: 25 with a current anxiety disorder and 63 children with epilepsy and no current anxiety disorder. Forty-nine controls without anxiety disorders were included. T1 volumetric magnetic resonance imaging (MRI) scans were collected; subcortical volumes and cortical thickness were computed using the FreeSurfer image analysis suite. Analyses focused on adjusted measures of subcortical volumes and cortical thickness.Relative to controls, larger left amygdala volumes were found in the Epilepsy with Anxiety group compared to the Epilepsy without Anxiety group (p = 0.027). In the hippocampus, there were no significant differences between groups. Examination of cortical thickness demonstrated that the Epilepsy with Anxiety group showed thinning in left medial orbitofrontal (p = 0.001), right lateral orbitofrontal (p = 0.017), and right frontal pole (p = 0.009). There were no differences between groups in age, sex, IQ, age of onset, medications, or duration of epilepsy. There were more family members with a history of anxiety disorders in the Epilepsy with Anxiety group compared to the Epilepsy without Anxiety group (p = 0.005).Anxiety is a common psychiatric comorbidity in children with recent-onset epilepsy with volumetric enlargement of the amygdala and thinner cortex in orbital and other regions of prefrontal cortex, suggesting structural abnormalities in brain regions that are part of the dysfunctional networks reported in individuals with anxiety disorders in the general population. These findings are evident early in the course of epilepsy, are not related to chronicity of seizures, and may be linked to a family history of anxiety and depressive disorders.

OBJECTIVE Adults with juvenile myoclonic epilepsy (JME) have subtle brain structural abnormalities in the frontothalamocortical network, poorer cognitive function, and worse long-term social outcomes, even when their seizures are controlled and/or remitted. The natural history of JME and development of abnormalities in brain structure and cognition from epilepsy onset has not been studied. METHODS The maturational trajectories of cognitive and brain development were prospectively compared between 19 children with new-onset JME in the first 2 years after diagnosis and 57 healthy controls. RESULTS Cognitive abilities of children with JME were similar to or worse than healthy controls at baseline but failed to reach the competence level of healthy controls at follow-up across most of the tested cognitive abilities. Abnormal patterns of brain development, as assessed by magnetic resonance imaging studies, were evident in children with JME and included attenuation of age-related decline in cortical volume, thickness, and surface area compared to typically developing children. The altered brain developmental trajectory in the JME group was evident in higher-association frontoparietotemporal brain regions (p < 0.05, corrected for multiple comparisons). INTERPRETATION Children with JME have abnormal structural brain development and impaired cognitive development early in the course of their epilepsy.

Recent neuroimaging and behavioral studies have revealed that children with new onset epilepsy already exhibit brain structural abnormalities and cognitive impairment. How the organization of large-scale brain structural networks is altered near the time of seizure onset and whether network changes are related to cognitive performances remain unclear. Recent studies also suggest that regional brain volume covariance reflects synchronized brain developmental changes. Here, we test the hypothesis that epilepsy during early-life is associated with abnormalities in brain network organization and cognition. We used graph theory to study structural brain networks based on regional volume covariance in 39 children with new-onset seizures and 28 healthy controls. Children with new-onset epilepsy showed a suboptimal topological structural organization with enhanced network segregation and reduced global integration compared with controls. At the regional level, structural reorganization was evident with redistributed nodes from the posterior to more anterior head regions. The epileptic brain network was more vulnerable to targeted but not random attacks. Finally, a subgroup of children with epilepsy, namely those with lower IQ and poorer executive function, had a reduced balance between network segregation and integration. Taken together, the findings suggest that the neurodevelopmental impact of new onset childhood epilepsies alters large-scale brain networks, resulting in greater vulnerability to network failure and cognitive impairment.

Summary Introduction Diffusion tensor imaging (DTI) studies have reported white matter abnormalities in childhood-onset epilepsy, but the mechanisms and timing underlying these abnormalities, and their resolution, are not well understood. This study examined white matter integrity in children with active versus remitted epilepsy. Methods Tract-based spatial statistics (TBSS) was used to examine whole-brain DTI indices of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in 20 children with epilepsy 5–6 years after diagnosis, compared to 29 healthy controls. To determine the status of white matter following cessation of seizures, participants with epilepsy were classified as active versus remitted and comparisons included: (1) controls versus all children with epilepsy, (2) controls versus children with remitted seizures, (3) controls versus children with active seizures, and (4) children with active versus remitted epilepsy. Results In the active compared to remitted epilepsy group, significantly higher FA and lower MD, AD and RD values were dispersed in the internal capsule, cingulum, body of the corpus callosum, superior corona radiata and superior fronto-occipital fasciculus. Similar differences were found between the active epilepsy and the control group. There were no significant differences between the remitted epilepsy and control groups. Conclusion Children with active epilepsy differed in white matter integrity compared to children with remitted epilepsy and healthy controls. It remains to be determined whether these findings represent the outcomes of seizure remission versus an initial biomarker for those children who will ultimately have intractable epilepsy.

The purpose of this investigation was to characterize the neuroanatomical correlates (cortical thickness) of variations in parent-reported Child Behavior Checklist (CBCL) scores. Ninety children with epilepsy (aged 8-18) underwent brain MRI, and their parents completed the CBCL. FreeSurfer-derived measures of cortical thickness were examined in relation to the CBCL broad and narrow band competence and behavioral problem scales, as well as the newer DSM-oriented scales. Parent reports of higher (better) social competence skills were associated with increased cortical thickness, especially in frontal regions. Parent reports of behavioral problems were associated with patterns of decreased cortical thickness that varied as a function of the specific behavioral issue under investigation. Congruence of patterns of cortical thinning between the DSM-oriented scales and conceptually related specific problem scales (e.g., ADHD Problems and Attention Problems) was generally weak. The parent-report version of the CBCL is associated with variations in cortical thickness among children with epilepsy. Anatomic abnormalities specific to selected competence and behavioral problem scales can be identified, with more reliable and robust patterns of thinning across scales assessing externalizing behaviors, with generally less prominent findings on scales assessing internalizing behaviors.

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 with 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 years, current chronological age = 56.0 years) and were compared with 48 population-based controls (mean age = 55.9 years). 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 with 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 with 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. Hum Brain Mapp 38:3289-3299, 2017. © 2017 Wiley Periodicals, Inc.

Children with uncomplicated idiopathic epilepsies often have IQ scores within the average range,1 but direct comparison of children with epilepsy with typically developing children frequently shows IQ to be significantly lower in the children with epilepsy.2 This IQ difference is usually attributed to the effect of epilepsy on cognition.3 The possibility a that lower IQ in children with idiopathic epilepsies may be related to genetic factors, socio-economic status, or other familial or environmental factors has not been examined to determine whether etiologies other than the epilepsy itself affect child IQ. It is important to consider cognitive scores in the context of the ability levels of other family members given the growing evidence of familial aggregation of learning and cognitive anomalies in the siblings and even parents of children with epilepsy.4–9 Further, when examining IQ, accounting for differences in parent IQ is an important consideration as the heritability of intelligence is well established,10,11 with some studies revealing that genetics can account for 40% to 60% of variance in IQ scores in normative populations.12,13 The ‘difference’ in IQ between parent and child could conceivably distinguish groups of children with average IQ scores. For example, in one child an average or even low average IQ might be congruent with parental IQ, whereas in another case a solidly average IQ might be significantly lower than the IQ of the parent. Considering the IQ difference between a child and a parent may provide a novel way of characterizing the cognitive impact of epilepsy, rather than examining only the child’s IQ in relation to a normative population. For this reason, a measure of child-to-parent cognitive scores could serve as a marker for the impact of a condition and its treatment, both at the time of diagnosis and over time. In the current study we examined parent–child IQ difference in order to further refine our understanding of the effects of epilepsy on cognition. First, the traditional comparison of IQ difference between children with epilepsy and healthy children was examined: the typical contrast used to ascertain ‘epilepsy impact’. Second, we made a series of novel comparisons including contrast between parents of the children with epilepsy and parents of the comparison children, followed by comparison of parent–child dyads in the epilepsy and comparison groups, the outcomes of which speak to the presence or absence of unique effects of epilepsy on child IQ. Finally, we focused on parent–child IQ differences in the epilepsy group only, in order to examine the effects of clinical seizure features (i.e. epilepsy syndrome, age at onset, antiepileptic medications). These comparisons are undertaken in children with new/recent-onset epilepsies, thereby addressing cognitive effects in a cohort unencumbered by the effects of chronic and intractable epilepsies.

SUMMARY Purpose: To characterize differences in brain structure and their patterns of age-related change in individuals with chronic childhood/adolescent onset temporal lobe epilepsy compared with healthy controls. Methods: Subjects included participants with chronic temporal lobe epilepsy (n = 55) of mean childhood/adolescent onset and healthy controls (n = 53), age 14–60 years. Brain magnetic resonance imaging (MRI) studies (1.5 T) were processed using FreeSurfer to obtain measures of lobar thickness, area, and volume as well as volumes of diverse subcortical structures and cerebellum. Group differences were explored followed by cross-sectional lifespan modeling as a function of age. Key Findings: Anatomic abnormalities were extensive in participants with chronic temporal lobe epilepsy including distributed subcortical structures (hippocampus, thalamus, caudate, and pallidum), cerebellar gray and white matter, total cerebral gray and white matter; and measures of cortical gray matter thickness, area, or volume in temporal (medial, lateral) and extratemporal lobes (frontal, parietal). Increasing chronologic age was associated with progressive changes in diverse cortical, subcortical, and cerebellar regions for both participants with epilepsy and controls. Age-accelerated changes in epilepsy participants were seen in selected areas (third and lateral ventricles), with largely comparable patterns of age-related change across other regions of interest. Significance: Extensive cortical, subcortical, and cerebellar abnormalities are present in participants with mean chronic childhood/adolescent onset temporal lobe epilepsy implicating a significant neurodevelopmental impact on brain structure. With increasing chronologic age, the brain changes occurring in epilepsy appear to proceed in a largely age-appropriate fashion compared to healthy controls, the primary exception being age-accelerated ventricular expansion (lateral and third ventricles). These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years.

Summary Purpose: Benign epilepsy with centrotemporal spikes (BECTS), the most common childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic influence. Despite its signature electroencephalographic pattern and distinct focal motor seizure semiology, little is known about the underlying brain anatomic alteration and the corresponding cognitive consequences. Given the motor manifestations of seizures in BECTS, we hypothesize that anatomic networks in BECTS involve a distributed corticostriatal circuit. Methods: We investigated volumetric differences and shape deformities of caudate, putamen, pallidum, and thalamus in a group of children with new- and recent-onset BECTS (N = 13) compared to healthy controls (N = 54). We correlated specific subcortical volumes in BECTS that were significantly different from those in healthy controls with performances in executive function. Key Findings: Children with BECTS demonstrated significantly hypertrophied putamen, which was selective among the subcortical regions examined. Shape analysis showed dorsoventral elongation of the left caudate and bilateral putamen, with subnuclei expansion in ventral and dorsal striatum. Larger putamen volumes were linked to better cognitive performances on two complementary executive function tests. Significance: Children with BECTS showed aberrant volume and shape in subcortical regions that are critical for both motor processing and executive function. It is of importance to note that the hypertrophy appears to be cognitively adaptive, as enlargement was associated with improved cognitive performances. The anatomic abnormalities and their cognitive effects are evident in a group of children with new- and recent-onset epilepsy, suggesting that the structural brain anomalies occurred before the diagnosis of epilepsy.

Abnormal expansion of the ventricular system has been observed in many neurologic and psychiatric disorders, including dementia (Carmichael et al., 2007), multiple sclerosis (Dalton et al., 2006) and autism spectrum disorder (Palmen et al., 2005). The natural history of ventricular enlargement and its consequences have been increasingly investigated, and in some disorders such as schizophrenia, enlargement is present at the onset of the disorder (Sowell et al., 2000; Vita et al., 2006) and progresses over time (Kempton et al., 2010). In the literature on aging, age-accelerated ventricular enlargement may herald the cognitive decline associated with the onset and progression of Alzheimer’s disease (Nestor et al., 2008). In 1917, Thom was the first to note ventricle enlargement in individuals with epilepsy; he reported lateral ventricle dilation following postmortem examinations of patients with idiopathic epilepsy (Thom, 1917). But over the decades, interest in the ventricular system has never matched that seen in other disorders. Recently, Kalnin et al. (2008) used a qualitative magnetic resonance imaging (MRI) scoring system to identify brain abnormalities in children with new-onset epilepsies. Interestingly, enlarged ventricles were the most common finding among those with imaging abnormalities (seen in 51% of abnormal scans), a potentially clinically significant finding as mild generalized cognitive impairment is present in new-onset pediatric epilepsy (Oostrom et al., 2003; Hermann et al., 2006; Fastenau et al., 2009). Herein we examine volumes of the third, fourth, and lateral ventricles in children with new/recent-onset idiopathic generalized (IGE) and idiopathic localization-related epilepsy (ILRE) and healthy controls (HCs). Shape analysis was subsequently used to determine whether identified volumetric abnormalities were diffuse or localized. A consecutive subset of children were seen 2 years later to facilitate examination of whether ventricle enlargement was progressive in nature or reflected a static neurodevelopmental abnormality.

Epilepsy is a prevalent childhood neurological disorder, but there are few prospective quantitative magnetic resonance imaging studies examining patterns of brain development compared to healthy controls. Controlled prospective investigations initiated at or near epilepsy onset would best characterize the nature, timing and course of neuroimaging abnormalities in paediatric epilepsy. In this study, we report the results of a deformation-based morphometry technique to examine baseline and 2-year prospective neurodevelopmental brain changes in children with new and recent onset localization-related epilepsies ( n = 24) and idiopathic generalized epilepsies ( n = 20) compared to healthy controls ( n = 36). Children with epilepsy demonstrated differences from controls in baseline grey and white matter volumes suggesting antecedent anomalies in brain development, as well as abnormal patterns of prospective brain development that involved not only slowed white matter expansion, but also abnormalities of cortical grey matter development involving both greater and lesser volume changes compared to controls. Furthermore, abnormal neurodevelopmental changes extended outside the cortex affecting several subcortical structures including thalamus, cerebellum, brainstem and pons. Finally, there were significant differences between the epilepsy syndromes (localization-related epilepsies and idiopathic generalized epilepsies) with the idiopathic generalized epilepsies group showing a more disrupted pattern of brain structure both at baseline and over the 2-year interval. * Abbreviations : IGE : idiopathic generalized epilepsies LRE : localization-related epilepsies

Summary Purpose: Research indicates that patients with chronic temporal lobe epilepsy (TLE) exhibit cerebellar atrophy compared to healthy controls, but the degree to which specific regions of the cerebellum are affected remains unclear. The purpose of this study was to characterize the extent and lateralization of atrophy in individual cerebellar lobes and subregions in unilateral TLE using advanced quantitative magnetic resonance imaging (MRI) techniques. Methods: Study participants were 46 persons with TLE and 31 age- and gender- matched healthy controls. All participants underwent high-resolution MRI with manual tracing of the cerebellum yielding gray and white matter volumes of the right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. The degree to which asymmetric versus generalized abnormalities was evident in unilateral chronic TLE was determined and related to selected clinical seizure features (age of onset, duration of disorder). Key Findings: There were no lateralized abnormalities in cerebellar gray matter or white matter in patients with right or left TLE (all p’s > 0.2). Compared with controls, unilateral TLE was associated with significant bilateral reductions in the superior (p = 0.032) and inferior (p = 0.023) posterior lobes, whereas volume was significantly increased in the anterior lobes (p = 0.002), especially in patients with early onset TLE, and not significantly different in the corpus medullare (p = 0.71). Total superior cerebellar tissue volumes were reduced in association with increasing duration of epilepsy. Significance: Patients with unilateral TLE exhibit a pattern of bilateral cerebellar pathology characterized by atrophy of the superior and inferior posterior lobes, hypertrophy of the anterior lobe, and no effect on the corpus medullare. Cross-sectional analyses show that specific aspects of cerebellar pathology are associated with neurodevelopmental (anterior lobe) or chronicity-related (superior posterior lobe) features of the disorder.

SUMMARY Purpose: To characterize prospective neurodevelopmental changes in brain structure in children with new and recent-onset epilepsy compared to healthy controls. Methods: Thirty-four healthy controls (mean age 12.9 years) and 38 children with new/recent-onset idiopathic epilepsy (mean age 12.9 years) underwent 1.5 T magnetic resonance imaging (MRI) at baseline and 2 years later. Prospective changes in total cerebral and lobar gray and white matter volumes were compared within and between groups. Results: Prospective changes in gray matter volume were comparable for the epilepsy and control groups, with significant (p 0.06). The group by white matter volume change interactions were significant for total cerebrum (p = 0.04) and frontal lobe (p = 0.04). Discussion: Children with new and recent-onset epilepsy exhibit an altered pattern of brain development characterized by delayed age-appropriate increase in white matter volume. These findings may affect cognitive development through reduced brain connectivity and may also be related to the impairments in executive function commonly reported in this population.

The purpose of this investigation was to examine the diffusion properties of cerebral white matter in children with recent onset epilepsy (n=19) compared to healthy controls (n=11). Subjects underwent DTI with quantification of mean diffusion (MD), fractional anisotropy (FA), axial diffusivity (D(ax)) and radial diffusivity (D(rad)) for regions of interest including anterior and posterior corpus callosum, fornix, cingulum, and internal and external capsules. Quantitative volumetrics were also performed for the corpus callosum and its subregions (anterior, midbody and posterior) and total lobar white and gray matter for the frontal, parietal, temporal and occipital lobes. The results demonstrated no group differences in total lobar gray or white matter volumes or volume of the corpus callosum and its subregions, but did show reduced FA and increased D(rad) in the posterior corpus callosum and cingulum. These results provide the earliest indication of microstructural abnormality in cerebral white matter among children with idiopathic epilepsies. This abnormality occurs in the context of normal volumetrics and suggests disruption in myelination processes.

Objective Previous research characterized three cognitive phenotypes in temporal lobe epilepsy, each associated with a different profile of clinical seizure and demographic characteristics, total cerebral (gray, white, cerebrospinal fluid) and hippocampal volumes, and prospective cognitive trajectories. The objective of this investigation was to characterize in detail the specific neuroanatomical abnormalities associated with each cognitive phenotype. Methods High-resolution MRI scans of healthy controls (n = 53) and patients with temporal lobe epilepsy (n = 55), grouped by cognitive phenotype (minimally impaired; memory impaired; memory, executive function, and speed impaired), were examined with respect to patterns of gray matter thickness throughout the cortical mantle, as well as volumes of subcortical structures, corpus callosum, and regions of the cerebellum. Results Increasing abnormalities in temporal and extratemporal cortical thickness, volumes of subcortical structures (hippocampus, thalamus, basal ganglia), all regions of the corpus callosum, and bilateral cerebellar gray matter distinguish the cognitive phenotypes in a generally stepwise fashion. The most intact anatomy is observed in the minimally impaired epilepsy group and the most abnormal anatomy is evident in the epilepsy group with impairments in memory, executive function, and speed. Conclusion Empirically derived cognitive phenotypes are associated with the presence, severity, and distribution of anatomic abnormalities in widely distributed cortical, subcortical, callosal, and cerebellar networks.

Summary Objective Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC). Methods Participants were 8–15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes. Results Baseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC. Significance Cognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time.

Production of 17F (t1/2=65 s) in the form of [17F] F2 has been achieved using both the 20Ne(p,alpha)17F and 16O(d,n)17F reactions with 11 MeV protons and 6 MeV deuterons, respectively. Yields have proven suitable for subsequent radiosynthesis of the blood flow tracer, [17F]CH3F (>60 mCi in saline), currently in use for fast repetition human studies of regional cerebral blood flow with positron emission tomography. Thick target yields of 15 mCi /microA for protons and 44 mCi/microA for deuterons have been measured for [17F]F2.

A new thin window support system for the accelerator production of positron emitters (e.g. 17 F, 18 F 11 C, 15 O) has been developed. The integrated support grid and cooling design has been optimized for 6–13 MeV protons or deuterons. The water-cooled support grid regularly operated at >100 μA of 6 MeV deuterons and protons. The grid performed without failure at ⩾50 μA of 13 MeV protons on a 3.1 MPa gas target using 25.4 μm aluminum target foil. Transmission for the smallest hole grid of 72% based on uniform parallel beam agreed with the measured yield of 71±1% compared to the theoretical maximum yield.

To determine correlations of the EEG frequency spectrum with neuropsychological status in children with idiopathic epilepsy.Forty-six children ages 8-18 years old with idiopathic epilepsy were retrospectively identified and analyzed for correlations between EEG spectra and neuropsychological status using multivariate linear regression. In addition, the theta/beta ratio, which has been suggested as a clinically useful EEG marker of attention-deficit hyperactivity disorder (ADHD), and an EEG spike count were calculated for each subject.Neuropsychological status was highly correlated with posterior alpha (8-15 Hz) EEG activity in a complex way, with both positive and negative correlations at lower and higher alpha frequency sub-bands for each cognitive task in a pattern that depends on the specific cognitive task. In addition, the theta/beta ratio was a specific but insensitive indicator of ADHD status in children with epilepsy; most children both with and without epilepsy have normal theta/beta ratios. The spike count showed no correlations with neuropsychological status.(1) The alpha rhythm may have at least two sub-bands which serve different purposes. (2) The theta/beta ratio is not a sensitive indicator of ADHD status in children with epilepsy. (3) The EEG frequency spectrum correlates more robustly with neuropsychological status than spike count analysis in children with idiopathic epilepsy.(1) The role of posterior alpha rhythms in cognition is complex and can be overlooked if EEG spectral resolution is too coarse or if neuropsychological status is assessed too narrowly. (2) ADHD in children with idiopathic epilepsy may involve different mechanisms from those in children without epilepsy. (3) Reliable correlations with neuropsychological status require longer EEG samples when using spike count analysis than when using frequency spectra.

The aim of this study was to determine the relationship between parent and child Full-scale IQ (FSIQ) in children with epilepsy and in typically developing comparison children and to examine parent-child IQ differences by epilepsy characteristics.The study participants were 97 children (50 males, 47 females; age range 8-18y; mean age 12y 3mo, SD 3y1mo) with recent-onset epilepsy including idiopathic generalized (n=43) and idiopathic localization-related epilepsies (n=54); 69 healthy comparison children (38 females, 31 males; age range 8-18y; mean age 12y 8mo, SD 3y 2mo), and one biological parent per child. All participants were administered the Wechsler Abbreviated Scale of Intelligence (WASI). FSIQ was compared in children with epilepsy and typically developing children; FSIQ was compared in the parents of typically developing children and the parents of participants with epilepsy; parent-child FSIQ differences were compared between the groups.FSIQ was lower in children with epilepsy than in comparison children (p0.001). FSIQ of parents of children with epilepsy did not differ from the FSIQ of the parents of typically developing children. Children with epilepsy had significantly lower FSIQ than their parents (p0.001), whereas comparison children did not. The parent-child IQ difference was significantly higher in the group with epilepsy than the comparison group (p=0.043). Epilepsy characteristics were not related to parent-child IQ difference.Parent-child IQ difference appears to be a marker of epilepsy impact independent of familial IQ, epilepsy syndrome, and clinical seizure features. This marker is evident early in the course of idiopathic epilepsies and can be tracked over time.

Benign epilepsy with centrotemporal spikes (BECTS), the most common childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic influence. Despite its signature electroencephalographic pattern and distinct focal motor seizure semiology, little is known about the underlying brain anatomic alteration and the corresponding cognitive consequences. Given the motor manifestations of seizures in BECTS, we hypothesize that anatomic networks in BECTS involve a distributed corticostriatal circuit.We investigated volumetric differences and shape deformities of caudate, putamen, pallidum, and thalamus in a group of children with new- and recent-onset BECTS (N = 3) compared to healthy controls (N = 54). We correlated specific subcortical volumes in BECTS that were significantly different from those in healthy controls with performances in executive function.Children with BECTS demonstrated significantly hypertrophied putamen, which was selective among the subcortical regions examined. Shape analysis showed dorsoventral elongation of the left caudate and bilateral putamen, with subnuclei expansion in ventral and dorsal striatum. Larger putamen volumes were linked to better cognitive performances on two complementary executive function tests.Children with BECTS showed aberrant volume and shape in subcortical regions that are critical for both motor processing and executive function. It is of importance to note that the hypertrophy appears to be cognitively adaptive, as enlargement was associated with improved cognitive performances. The anatomic abnormalities and their cognitive effects are evident in a group of children with new- and recent-onset epilepsy, suggesting that the structural brain anomalies occurred before the diagnosis of epilepsy.

To examine baseline and prospective (2-year) changes in third, fourth, and lateral ventricle volumes in children with new-onset idiopathic epilepsies and controls (age 8-18 years).Structural magnetic resonance imaging (MRI) were collected from children with idiopathic generalized epilepsy (IGE, n = 29), idiopathic localization-related epilepsy (ILRE, n = 30), and healthy controls (HCs, n = 49). Volumes of the third, fourth, and lateral ventricles were derived and compared across groups, followed by shape analyses, to identify specific regions of ventricular abnormality. Of the initial cohort, a consecutive sample of 71 children returned 2 years later for reimaging and determination of progressive changes in the ventricular system.At baseline, children with new-onset IGE had significantly larger lateral and third ventricle volumes relative to the HC group. In addition, lateral ventricle enlargement in IGE was significantly greater compared to new-onset ILRE. Shape analysis of the lateral ventricles revealed that volume expansion in IGE was selective for the anterior horn, a region surrounded by the lateral and medial frontal lobes as well as basal ganglia. These abnormalities did not progress over a 2-year interval.Abnormalities in brain development prior to onset and diagnosis of epilepsy are evident and reflected in expansion of the ventricular system, especially among children with IGE. These abnormalities appear to represent an antecedent and possibly static finding given the lack of progressive ventricular expansion over the 2-year interval following diagnosis and treatment.

Research indicates that patients with chronic temporal lobe epilepsy (TLE) exhibit cerebellar atrophy compared to healthy controls, but the degree to which specific regions of the cerebellum are affected remains unclear. The purpose of this study was to characterize the extent and lateralization of atrophy in individual cerebellar lobes and subregions in unilateral TLE using advanced quantitative magnetic resonance imaging (MRI) techniques.Study participants were 46 persons with TLE and 31 age- and gender- matched healthy controls. All participants underwent high-resolution MRI with manual tracing of the cerebellum yielding gray and white matter volumes of the right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. The degree to which asymmetric versus generalized abnormalities was evident in unilateral chronic TLE was determined and related to selected clinical seizure features (age of onset, duration of disorder).There were no lateralized abnormalities in cerebellar gray matter or white matter in patients with right or left TLE (all p's0.2). Compared with controls, unilateral TLE was associated with significant bilateral reductions in the superior (p = 0.032) and inferior (p = 0.023) posterior lobes, whereas volume was significantly increased in the anterior lobes (p = 0.002), especially in patients with early onset TLE, and not significantly different in the corpus medullare (p = 0.71). Total superior cerebellar tissue volumes were reduced in association with increasing duration of epilepsy.Patients with unilateral TLE exhibit a pattern of bilateral cerebellar pathology characterized by atrophy of the superior and inferior posterior lobes, hypertrophy of the anterior lobe, and no effect on the corpus medullare. Cross-sectional analyses show that specific aspects of cerebellar pathology are associated with neurodevelopmental (anterior lobe) or chronicity-related (superior posterior lobe) features of the disorder.

Background: Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined. Objective: We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis). Methods: We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes. Results: The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained. Conclusions: Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval.

Functional neurochemical imaging can indicate neurotransmitter release by detecting changes in receptor occupancy. A dual tracer positron emission tomography (PET) technique is presented here to extend such studies by simultaneously measuring changes in regional cerebral blood flow (rCBF). This would permit correlations of task or drug induced changes in rCBF and neurochemical function. In this proposed method, the rapidly varying signal from a blood flow tracer is distinguished from the slowly changing signal due to a long-lived neurochemical tracer. As a proof of principle, baseline studies were carried out in rhesus monkeys. Two monkeys were anesthetized with isoflurane, and [ 18 F ]fallypride (t1/2=110 min), a dopamine D2 receptor antagonist, was injected. Starting 99–137 min after injection, PET images were acquired every 10 s while the blood flow tracer [ 17 F ]fluoromethane (t1/2=65 s) was administered by inhalation in a repeating pattern of 45 s on/45 s off. The observed time–activity curves for 2 ml brain regions were fit with a three compartment lung–body–brain model of fluoromethane kinetics with whole brain perfusion fixed. Comparing consecutive 6 min scans, reproducibility of relative rCBF and striatal [ 18 F ]fallypride concentration were 9 and 8%, respectively.

Objective To characterize neuropsychological and academic status in children, ages 8-18 years, with new-/recent-onset idiopathic generalized epilepsy (IGE) and idiopathic localization-related epilepsy (ILRE) compared with healthy controls. Study design Participants underwent neuropsychological assessment, and parents were interviewed regarding their child's academic history. Cognitive scores for children with epilepsy were age- and sex-adjusted and compared with controls across both broad-band (IGE n = 41 and ILRE n = 53) and narrow-band (childhood/juvenile absence, juvenile myoclonic, benign epilepsy with centro-temporal spikes, and focal [temporal/frontal/not otherwise specified]) syndromes. Academic histories were examined, including problems antecedent to epilepsy onset and diagnosis. Results Children with new/recent-onset epilepsies exhibit considerable cognitive abnormality at baseline, including patterns of shared abnormalities across syndromes (eg, psychomotor slowing) as well as unique syndrome-specific cognitive effects (eg, executive function in IGE and language/verbal memory in ILRE) that are observed and sometimes exacerbated in specific IGE and ILRE syndromes. Academic difficulties are evident in approximately 50% of the children with epilepsy, affecting all syndrome groups to an equal degree. Discussion Patterns of shared and syndrome-specific cognitive abnormalities and academic problems are present early in the course of virtually all epilepsy syndromes examined here, including syndromes classically viewed as benign. This is the base upon which the effects of recurrent seizures, treatment, and psychosocial effects will be added over time.