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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.

Objective To identify cognitive phenotypes in temporal lobe epilepsy (TLE) and test their reproducibility in a large, multi-site cohort of patients using both data-driven and clinically driven approaches. Method Four-hundred seven patients with TLE who underwent a comprehensive neuropsychological evaluation at one of four epilepsy centers were included. Scores on tests of verbal memory, naming, fluency, executive function, and psychomotor speed were converted into z-scores based on 151 healthy controls (HCs). For the data-driven method, cluster analysis (k-means) was used to determine the optimal number of clusters. For the clinically driven method, impairment was defined as >1.5 standard deviations below the mean of the HC, and patients were classified into groups based on the pattern of impairment. Results Cluster analysis revealed a three-cluster solution characterized by (a) generalized impairment (29%), (b) language and memory impairment (28%), and (c) no impairment (43%). Based on the clinical criteria, the same broad categories were identified, but with a different distribution: (a) generalized impairment (37%), (b) language and memory impairment (30%), and (c) no impairment (33%). There was a 82.6% concordance rate with good agreement (κ = .716) between the methods. Forty-eight patients classified as having a normal profile based on cluster analysis were classified as having generalized impairment (n = 16) or an isolated language/memory impairment (n = 32) based on the clinical criteria. Patients with generalized impairment had a longer disease duration and patients with no impairment had more years of education. However, patients demonstrating the classic TLE profile (ie, language and memory impairment) were not more likely to have an earlier age at onset or mesial temporal sclerosis. Significance We validate previous findings from single-site studies that have identified three unique cognitive phenotypes in TLE and offer a means of translating the patterns into a clinical diagnostic criteria, representing a novel taxonomy of neuropsychological status in TLE.

Purpose To characterize the impact of slowed processing speed on the efficiency of broader cognitive function in temporal lobe epilepsy (TLE). Methods Participants included 100 patients with TLE and 89 healthy controls (mean ages 36.8 and 33.6, respectively) administered a neuropsychological battery consisting of 15 cognitive metrics. Confirmatory factor analysis using structural equation modeling (SEM) latent variable modeling demonstrated a cognitive structure representing the domains of verbal intelligence, immediate memory, delayed memory, executive function, working memory, and processing speed. Furthermore, the latent variable measurement model determined the direct and indirect relationships of verbal intelligence and processing speed with immediate memory, delayed memory, executive function, and working memory. Results Following SEM of hypothesized structural models, the results demonstrated that, among controls, intelligence had a direct and unmediated (by processing speed) relationship with all identified cognitive domains. In contrast, among participants with TLE, processing speed mediated the relationship between verbal intelligence and performance across all cognitive domains. Conclusion Slowing of cognitive/psychomotor processing speed appears to play a critical mediating role in the broader cognitive status of participants with TLE and may serve as a target through which to attempt to exert a broad positive impact on neuropsychological status.

Objective The greater resilience of older memories relative to recent memories has primarily been demonstrated in clinical groups, but this phenomenon has been less extensively examined in cognitively intact older adults. Additionally, most studies of person-identity have only examined recognition or familiarity of a famous face or name, and there has been less systematic study of access to more specific person-identity semantic knowledge. The current study examined the effect of both memory age and extent of semantic knowledge on famous name recognition and retrieval of person-identity biographical information in healthy older adults. Method We examined recognition accuracy and response time of famous names at three time epochs (recent fame, transitory fame and enduring fame) in cognitively intact older adults. We also compared access to semantic knowledge that differed on the degree of specificity of biographical information: categorical, associative, and attribute knowledge. Results As predicted, participants recognized transitory famous names more quickly and accurately than recent famous names. Additionally, participants recognized enduring famous names more accurately than transitory famous names and recent names. We also found that categorical semantic knowledge was accessed more quickly and accurately than semantic knowledge for associative and attribute information. Conclusions These findings provide data on the cognitive structure and retrieval of person-identity knowledge and memory age in older cognitively intact individuals.

Objective:The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI.Methods:Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted toz-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes.Results:At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion.Conclusions:Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

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

AIM: To determine whether the first degree cousins of children with idiopathic focal and genetic generalized epilepsies (cases) show any association across measures of cognition, behavior and brain structure. The presence/absence of associations addresses the question of whether and to what degree first degree cousins may serve as unbiased controls in research addressing the cognitive, psychiatric, and neuroimaging features of pediatric epilepsies. METHODS: Participants were children (age 8 – 18) with epilepsy who had at least one first-degree cousin control enrolled in the study (n=37) and all enrolled cousin controls (n=100). Participants underwent neuropsychological assessment, brain imaging (cortical, subcortical and cerebellar volumes) and parents completed the Child Behavior Checklist (CBCL). Data (42 outcome measures) from cousin controls were regressed on the corresponding epilepsy cognitive, behavioral and imaging measures in a linear mixed model and case – control correlations were examined. RESULTS: Of the 42 uncorrected correlations involving cognitive, behavioral and neuroimaging measures, only 2 were significant (p 0.25). Similar results held for the cognition/behavior and brain imaging measures separately. CONCLUSIONS: Given the lack of association between cases and first degree cousin performances on measures of cognition, behavior and neuroimaging, the results suggest a non-significant genetic influence on control group performance. First -degree cousins appear to be unbiased controls for cognitive, behavioral, and neuroimaging research in pediatric epilepsy.

Intraindividual variability (IIV) in motor performance has been shown to predict future cognitive decline. The apolipoprotein E-epsilon 4 (APOE-ε4) allele is also a well-established risk factor for memory decline. Here, we present novel findings examining the influence of the APOE-ε4 allele on the performance of asymptomatic healthy elders in comparison to individuals with amnestic MCI (aMCI) on a fine motor synchronization, paced finger-tapping task (PFTT).Two Alzheimer's disease (AD) risk groups, individuals with aMCI (n = 24) and cognitively intact APOE-ε4 carriers (n = 41), and a control group consisting of cognitively intact APOE-ε4 noncarriers (n = 65) completed the Rey Auditory Verbal Learning Test and the PFTT, which requires index finger tapping in synchrony with a visual stimulus (interstimulus interval = 333 ms).Motor timing IIV, as reflected by the standard deviation of the intertap interval (ITI), was greater in the aMCI group than in the two groups of cognitively intact elders; in contrast, all three groups had statistically equivalent mean ITI. No significant IIV differences were observed between the asymptomatic APOE-ε4 carriers and noncarriers. Poorer episodic memory performance was associated with greater IIV, particularly in the aMCI group.Results suggest that increased IIV on a fine motor synchronization task is apparent in aMCI. This IIV measure was not sensitive in discriminating older asymptomatic individuals at genetic risk for AD from those without such a genetic risk. In contrast, episodic memory performance, a well-established predictor of cognitive decline in preclinical AD, was able to distinguish between the two cognitively intact groups based on genetic risk.

Accumulating evidence suggests that considerable cognitive and psychiatric comorbidity is associated with juvenile myoclonic epilepsy, for which the etiology remains controversial. Our goal was to comprehensively characterize the status of multiple neurobehavioral comorbidities in youth with new- or recent-onset juvenile myoclonic epilepsy, before effects of chronic seizures and medications.A total of 111 children aged eight to 18 years (41 new- or recent-onset juvenile myoclonic epilepsy and 70 first-degree cousin controls) underwent neuropsychological assessment (attention, executive, verbal, perceptual, speed), structured review of need for supportive academic services, parent reports of behavior and executive function (Child Behavior Checklist and Behavior Rating Inventory of Executive Function), and formal structured psychiatric interview and diagnosis (Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version).Children with juvenile myoclonic epilepsy performed worse than controls across all tested cognitive domains (F(1,105) = 3.85, P 0.01), utilized more academic services (47% versus 19%, P = 0.002), had more parent-reported behavioral problems and dysexecutive function with lower competence (P 0.001), and had a higher prevalence of current Axis I diagnoses (attention-deficit/hyperactivity disorder, depression, and anxiety; 54% versus 23%, P = 0.001). Academic and psychiatric problems occurred antecedent to epilepsy onset compared with comparable timeline in controls.Comprehensive assessment of cognitive, academic, behavioral, and psychiatric comorbidities in youth with new- or recent-onset juvenile myoclonic epilepsy reveals a pattern of significantly increased neurobehavioral comorbidities across a broad spectrum of areas. These early evident comorbidities are of clear clinical importance with worrisome implications for future cognitive, behavioral, and social function. It is important for health care providers to avoid delays in intervention by assessing potential comorbidities early in the course of the disorder to optimize their patients' social, academic and behavioral progress.

Objectives: White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer’s disease (AD). Methods: Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1–5, immediate recall, and delayed recall scores and baseline DTI measures; MTL gray matter (GM) and WM volumes; demographics; and AD genetic and metabolic risk factors. Results: Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, FH, and metabolic risk factors did not. Both ε4 status and DTI correlated with change in immediate recall. Conclusions: Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD. (JINS, 2016, 22, 1005–1015)

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.

Older adult apolipoprotein E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer’s disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.

OBJECTIVE The apolipoprotein E (APOE) e4 allele is the most important genetic risk factor for late-onset Alzheimer's disease. Many e4 carriers, however, never develop Alzheimer's disease. The purpose of this study is to characterize the variability in phenotypic expression of the e4 allele, as measured by the longitudinal trajectory of cognitive test scores and MRI brain volumes, in cognitively intact elders. METHOD Healthy older adults, ages 65-85, participated in a 5-year longitudinal study that included structural MRI and cognitive testing administered at baseline and at 1.5 and 5 years postenrollment. Participants included 22 e4 noncarriers, 15 e4 carriers who experienced a decline in cognition over the 5-year interval, and 11 e4 carriers who remained cognitively stable. RESULTS No baseline cognitive or volumetric group differences were observed. Compared to noncarriers, declining e4 carriers had significantly greater rates of atrophy in left (p = .001, Cohen's d = .691) and right (p = .003, d = .622) cortical gray matter, left (p = .003, d = .625) and right (p = .020, d = .492) hippocampi, and greater expansion of the right inferior lateral ventricle (p < .001, d = .751) over 5 years. CONCLUSIONS This study illustrates the variability in phenotypic expression of the e4 allele related to neurodegeneration. Specifically, only those individuals who exhibited longitudinal declines in cognitive function experienced concomitant changes in brain volume. Future research is needed to better understand the biological and lifestyle factors that may influence the expression of the e4 allele. (PsycINFO Database Record

Objectives:Rates of cognitive, academic and behavioral comorbidities are elevated in children with epilepsy. The contribution of environmental and genetic influences to comorbidity risk is not fully understood. This study investigated children with epilepsy, their unaffected siblings, and controls to determine the presence and extent of risk associated with family relatedness across a range of epilepsy comorbidities.Methods:Participants were 346 children (8–18 years),n=180 with recent-onset epilepsy, their unaffected siblings (n=67), and healthy first-degree cousin controls (n=99). Assessments included: (1) Child Behavior Checklist/6-18 (CBCL), (2) Behavior Rating Inventory of Executive Function (BRIEF), (3) history of education and academic services, and (4) lifetime attention deficit hyperactivity disorder (ADHD) diagnosis. Analyses consisted of linear mixed effect models for continuous variables, and logistic mixed models for binary variables.Results:Differences were detected between the three groups of children across all measures (pConclusions:The contribution of epilepsy and family relatedness varies across specific neurobehavioral comorbidities. Family relatedness was not significantly associated with rates of ADHD, academic problems and executive dysfunction, but was associated with competence and behavioral problems. (JINS, 2018,24, 1–9)

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.

Attentional vigilance, the ability to maintain focus over time, is frequently impaired in childhood epilepsy. Typically, indices of Omissions (failure to detect a target) and Commissions (responding to a nontarget) are considered primary indices of attentional vigilance. Recently, the concept of intraindividual variability (IIV) has been identified as an important measure of attentional vigilance in several pediatric and adult clinical populations, but has not yet been systematically examined in childhood epilepsy. Here, we examined IIV on the Connors Continuous Performance Task-II (CCPT-II) for 144 newly diagnosed children with epilepsy (age 8-18years) and a matched age group of healthy children (n=82). Intraindividual variability showed a large effect size difference (d=0.68) between groups. In addition, IIV significantly predicted both intellectual functioning and academic achievement. These findings support the utility of examining IIV in the assessment of attentional ability in childhood epilepsy.

In more recent years, studies have begun to examine levels of satisfaction of individuals or family members of individuals who undergo neuropsychological evaluation. However, to date there have been only a handful of formal studies that have specifically examined the role and contribution of neuropsychological assessment in patient care and management. This study sought to examine one specific component of neuropsychological assessment, namely the impact of patient feedback regarding neuropsychological testing on patient outcome.Participants included 218 patients who were recruited from a neuropsychological outpatient clinic at a Midwest academic medical center. This study examined potential differences between outcome measures for patients who attended feedback sessions versus those who did not receive direct feedback.Results indicated that compared with the No Feedback group, the Feedback group reported greater improvement in quality of life, increased understanding of their condition, and an increased ability to cope with their condition at follow-up. There were no significant demographic differences between the Feedback and No Feedback group.These findings suggest that there is benefit for the individuals who chose to engage in feedback sessions. Feedback sessions can be utilized to assist with integral decision-making processes and assisting in treatment planning among other areas. It also allows time for patients and family members to discuss their concerns regarding important test findings and recommendations. Given the current climate of value-based services and clinical outcomes, the findings from this study lend support to the utility of neuropsychological assessments and, in particular, the role of feedback within neuropsychological evaluations.

Neuropathological changes associated with Alzheimer's disease (AD) precede symptom onset by more than a decade. Possession of an apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for late onset AD. Cross-sectional studies of cognitively intact elders have noted smaller hippocampal/medial temporal volumes in ɛ4 carriers (ɛ4+) compared to ɛ4 non-carriers (ɛ4-). Few studies, however, have examined long-term, longitudinal, anatomical brain changes comparing healthy ɛ4+ and ɛ4- individuals. The current five-year study examined global and regional volumes of cortical and subcortical grey and white matter and ventricular size in 42 ɛ4+ and 30 ɛ4- individuals. Cognitively intact participants, ages 65-85 at study entry, underwent repeat anatomical MRI scans on three occasions: baseline, 1.5, and 4.75 years. Results indicated no between-group volumetric differences at baseline. Over the follow-up interval, the ɛ4+ group experienced a greater rate of volume loss in total grey matter, bilateral hippocampi, right hippocampal subfields, bilateral lingual gyri, bilateral parahippocampal gyri, and right lateral orbitofrontal cortex compared to the ɛ4- group. Greater loss in grey matter volumes in ɛ4+ participants were accompanied by greater increases in lateral, third, and fourth ventricular volumes. Rate of change in white matter volumes did not differentiate the groups. The current results indicate that longitudinal measurements of brain atrophy can serve as a sensitive biomarker for identifying neuropathological changes in persons at genetic risk for AD and potentially, for assessing the efficacy of treatments designed to slow or prevent disease progression during the preclinical stage of AD.

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.

Summary Objective Birth weight is an important indicator of prenatal environment, and subtle variations of birth weight within the normal range have been associated with differential risk for cognitive and behavioral problems. Therefore, we aimed to determine if there are differences in birth weight between full-term children with uncomplicated new/recent-onset epilepsies and typically developing healthy controls. We further examined the relationships between birth weight and childhood/adolescent cognition, behavior, and academic achievement. Methods One hundred eight children with new-onset/recent-onset epilepsy and 70 healthy controls underwent neuropsychological assessment. All participants were born full-term (>37 weeks) without birth complications. Parents were interviewed regarding their child's gestation, birth, and neurodevelopmental history. Results Birth weight of children with epilepsy was significantly lower than healthy controls (p = 0.023). Whereas birth weight (covaried with age, sex, handedness, and mother's education) was significantly associated with cognition in controls in multiple domains (intelligence, language, aspects of academic achievement), this relationship was absent in children with epilepsy. Birth weight was not associated with clinical epilepsy variables (age of onset, epilepsy syndrome) and was not predictive of a variety of other academic or psychiatric comorbidities of epilepsy. Significance Although the origin of lower birth weight in children with epilepsy is unknown, these findings raise the possibility that abnormal prenatal environment may affect childhood-onset epilepsy. Furthermore, the positive relationship between birth weight and cognition evident in healthy controls was disrupted in children with epilepsy. However, birth weight was not related to academic and psychiatric comorbidities of childhood epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

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.

Summary Cognitive and psychomotor slowing is a complication of epilepsy and is less often a focus of investigation relative to other cognitive domains (e.g., memory). A diversity of tasks has been used to examine psychomotor slowing in epilepsy, but it remains unknown whether the degree of epilepsy-related slowing is fixed or is exacerbated with increasing task demand. Also unknown is to what degree age related slowing is accelerated in epilepsy. Participants with temporal lobe epilepsy ( n =50) were compared to healthy controls ( n =69) across three tasks of psychomotor speed with varied complexity. Performance was examined as a function of group (epilepsy, controls), task complexity (simple, intermediate, complex), and chronological age. The results showed that speed of performance declined across the epilepsy and control participants as a function of task complexity. Epilepsy participants were significantly slower than controls across the three tasks, and there was a significant three-way interaction (group by task complexity by age). These results demonstrate that psychomotor slowing is related to task complexity in both epilepsy and healthy control participants, always greater in epilepsy participants, and there is a significant age acceleration of psychomotor slowing in the epilepsy group that is magnified by complex tasks.

Purpose To examine the impact of diverse syndromes of focal and generalized epilepsy on language function in children with new and recent onset epilepsy. Of special interest was the degree of shared language abnormality across epilepsy syndromes and the unique effects associated with specific epilepsy syndromes. Methods Participants were 136 youth with new or recent-onset (diagnosis within past 12 months) epilepsy and 107 healthy first-degree cousin controls. The participants with epilepsy included 20 with Temporal Lobe Epilepsy (TLE; M age = 12.99 years, SD = 3.11), 41 with Benign Epilepsy with Centrotemporal Spikes (BECTS; M age = 10.32, SD = 1.67), 42 with Juvenile Myoclonic Epilepsy (JME; M age = 14.85, SD = 2.75) and 33 with absence epilepsy (M age = 10.55, SD = 2.76). All children were administered a comprehensive test battery which included multiple measures of language and language-dependent abilities (i.e., verbal intelligence, vocabulary, verbal reasoning, object naming, reception word recognition, word reading, spelling, lexical and semantic fluency, verbal list learning and delayed verbal memory). Test scores were adjusted for age and gender and analyzed via MANCOVA. Results Language abnormalities were found in all epilepsy patient groups. The most broadly affected children were those with TLE and absence epilepsy, whose performance differed significantly from controls on 8 of 11 and 9 of 11 tests respectively. Although children with JME and BECTS were less affected, significant differences from controls were found on 4 of 11 tests each. While each group had a unique profile of language deficits, commonalities were apparent across both idiopathic generalized and localization-related diagnostic categories. Discussion The localization related and generalized idiopathic childhood epilepsies examined here were associated with impact on diverse language abilities early in the course of the disorder.

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.

Background: Engagement in cognitively stimulating activities (CA) and leisure time physical activity (PA) have been associated with maintaining cognitive performance and reducing the likelihood of cognitive decline in older adults. However, neural mechanisms underlying protective effects of these lifestyle behaviors are largely unknown. In the current study, we investigated the effect of self-reported PA and CA on hippocampal volume and semantic processing activation during a fame discrimination task, as measured by functional magnetic resonance imaging (fMRI). We also examined whether possession of the apolipoprotein E (APOE) ?4 allele could moderate the effect of PA or CA on hippocampal structure or function. Methods: Seventy-eight healthy, cognitively intact older adults underwent baseline neuropsychological assessment, hippocampal volume measurement via manually-traced structural MRI, and task-activated fMRI. Results: After 18 months, 27 participants declined by one standard deviation or more on follow-up neuropsychological testing. Logistic regression analyses revealed that CA alone or in combination with baseline hippocampal structure or functional activity did not predict the probability of cognitive decline. In contrast, PA interacted with APOE 4 status such that engagement in PA reduced the risk of cognitive decline in APOE 4 carriers only. Furthermore, the benefits of PA appeared to diminish with reduced functional activity or volume in the hippocampus. Conclusions: Our findings suggest that increased leisure time PA is associated with reduced probability of cognitive decline in persons who are at high risk for AD. The beneficial effects of PA in this group may be related to enhancement of the functional and structural integrity of the hippocampus.

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.

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer's disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

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.

Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6 -18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores.

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.

Chronic temporal lobe epilepsy (TLE) is characterized by the presence of extra-hippocampal brain abnormality and cognitive impairment in both memory and nonmemory domains. However, the link between structural integrity and cognition has not frequently been studied. Forty-six patients with TLE and 61 age-matched controls were studied to determine the predictive relationship between baseline thalamic volume and performance on measures of executive functioning evaluated 4 years later. As expected, the TLE group had lower baseline thalamic volumes than controls and also performed more poorly on measures of executive functioning. Total thalamic volume significantly predicted subsequent performance on all three measures of executive functioning. These findings were maintained when both hippocampal volume and frontal lobe volume were taken into account. These findings add to a growing literature demonstrating a link between extra-hippocampal volume abnormalities and cognitive functioning in TLE.

Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related functional-MRI in 17 healthy participants to directly compare activation in response to randomly presented famous and non-famous names and faces (25 stimuli in each of the four categories). Findings indicated distinct areas of activation that differed for faces and names in regions typically associated with pre-semantic perceptual processes. In contrast, overlapping brain regions were activated in areas associated with the retrieval of biographical knowledge and associated social affective features. Specifically, activation for famous faces was primarily right lateralized and famous names were left lateralized. However, for both stimuli, similar areas of bilateral activity were observed in the early phases of perceptual processing. Activation for fame, irrespective of stimulus modality, activated an extensive left hemisphere network, with bilateral activity observed in the hippocampi, posterior cingulate, and middle temporal gyri. Findings are discussed within the framework of recent proposals concerning the neural network of person identification.