Arterial spin labeled perfusion MRI for the assessment of radiation-treated meningiomas.

Purpose: Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. Methods: Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. Results: All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597). Conclusions: ASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials.

Impact of white matter networks on risk for memory decline following resection versus ablation in temporal lobe epilepsy.

BACKGROUND: With expanding neurosurgical options in epilepsy, it is important to characterise each options' risk for postoperative cognitive decline. Here, we characterise how patients' preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries. METHODS: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF)). RESULTS: Preoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01). CONCLUSIONS: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline.

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to frontal lobe epilepsy using multicenter data.

RATIONALE: The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. METHODS: Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. RESULTS: The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23-40% cognitively intact, 24-29% single domain impairment, 13-20% bi-domain impairment, and 18-33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15-18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. CONCLUSIONS: These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.

The relationship between mood and anxiety and cognitive phenotypes in adults with pharmacoresistant temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) are often at a high risk for cognitive and psychiatric comorbidities. Several cognitive phenotypes have been identified in TLE, but it is unclear how phenotypes relate to psychiatric comorbidities, such as anxiety and depression. This observational study investigated the relationship between cognitive phenotypes and psychiatric symptomatology in TLE. METHODS: A total of 826 adults (age = 40.3, 55% female) with pharmacoresistant TLE completed a neuropsychological evaluation that included at least two measures from five cognitive domains to derive International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) cognitive phenotypes (i.e., intact, single-domain impairment, bi-domain impairment, generalized impairment). Participants also completed screening measures for depression and anxiety. Psychiatric history and medication data were extracted from electronic health records. Multivariable proportional odds logistic regression models examined the relationship between IC-CoDE phenotypes and psychiatric variables after controlling for relevant covariates. RESULTS: Patients with elevated depressive symptoms had a greater odds of demonstrating increasingly worse cognitive phenotypes than patients without significant depressive symptomatology (odds ratio [OR] = 1.123-1.993, all corrected p's < .05). Number of psychotropic (OR = 1.584, p < .05) and anti-seizure medications (OR = 1.507, p < .001), use of anti-seizure medications with mood-worsening effects (OR = 1.748, p = .005), and history of a psychiatric diagnosis (OR = 1.928, p < .05) also increased the odds of a more severe cognitive phenotype, while anxiety symptoms were unrelated. SIGNIFICANCE: This study demonstrates that psychiatric factors are not only associated with function in specific cognitive domains but also with the pattern and extent of deficits across cognitive domains. Results suggest that depressive symptoms and medications are strongly related to cognitive phenotype in adults with TLE and support the inclusion of these factors as diagnostic modifiers for cognitive phenotypes in future work. Longitudinal studies that incorporate neuroimaging findings are warranted to further our understanding of the complex relationships between cognition, mood, and seizures and to determine whether non-pharmacologic treatment of mood symptoms alters cognitive phenotype.

Memory deficit following resection of an intraventricular myxoid glioneuronal tumor impinging on the bilateral fornix: A case report.

Background: Recently recognized as a distinct entity, a myxoid glioneuronal tumor (MGNT) is a rare, low-grade central nervous system tumor. MGNTs are commonly located at the septum pellucidum or in the third ventricle, increasing the likelihood of tumor or treatment-related damage to adjacent structures critical for memory, such as the fornix. Though there have been a handful of case reports of neurosurgical and oncological outcomes of MGNTs, memory outcomes following resection of MGNTs adjacent to the fornix have not been previously reported. Methods: We present a case of a high functioning female for whom an MRI revealed an incidental finding of an intraventricular tumor adjacent to the fornix bilaterally. The patient underwent resection of the tumor followed by MRI surveillance without additional oncologic intervention. Due to reported cognitive problems, the patient was referred for serial neuropsychological evaluations. Results: Post-operative MRI following resection revealed cytotoxic edema followed by selective, progressive atrophy of the bilateral anterior fornices. Post-surgically, the patient developed an isolated verbal memory impairment, which persisted one-year post resection with minimal improvement. The memory impairment impacted the patient's everyday functioning, including the ability to work in a cognitively demanding job. Conclusion: This unique case demonstrates the critical role of the bilateral fornix in verbal memory and underscores the importance of a careful risk/benefit analysis when considering neurosurgical intervention to MGNTs and other intracranial lesions adjacent to this structure during neurosurgical planning.

Cognitive phenotypes in late-onset epilepsy: results from the atherosclerosis risk in communities study.

Introduction: Cognitive phenotyping is a widely used approach to characterize the heterogeneity of deficits in patients with a range of neurological disorders but has only recently been applied to patients with epilepsy. In this study, we identify cognitive phenotypes in older adults with late-onset epilepsy (LOE) and examine their demographic, clinical, and vascular profiles. Further, we examine whether specific phenotypes pose an increased risk for progressive cognitive decline. Methods: Participants were part of the Atherosclerosis Risk in Communities Study (ARIC), a prospective longitudinal community-based cohort study of 15,792 individuals initially enrolled in 1987-1989. LOE was identified from linked Centers for Medicare and Medicaid Services claims data. Ninety-one participants with LOE completed comprehensive testing either prior to or after seizure onset as part of a larger cohort in the ARIC Neurocognitive Study in either 2011-2013 or 2016-2017 (follow-up mean = 4.9 years). Cognitive phenotypes in individuals with LOE were derived by calculating test-level impairments for each participant (i.e., ≤1 SD below cognitively normal participants on measures of language, memory, and executive function/processing speed); and then assigning participants to phenotypes if they were impaired on at least two tests within a domain. The total number of impaired domains was used to determine the cognitive phenotypes (i.e., Minimal/No Impairment, Single Domain, or Multidomain). Results: At our baseline (Visit 5), 36.3% met criteria for Minimal/No Impairment, 35% for Single Domain Impairment (with executive functioning/ processing speed impaired in 53.6%), and 28.7% for Multidomain Impairment. The Minimal/No Impairment group had higher education and occupational complexity. There were no differences in clinical or vascular risk factors across phenotypes. Of those participants with longitudinal data (Visit 6; n = 24), 62.5% declined (i.e., progressed to a more impaired phenotype) and 37.5% remained stable. Those who remained stable were more highly educated compared to those that declined. Discussion: Our results demonstrate the presence of identifiable cognitive phenotypes in older adults with LOE. These results also highlight the high prevalence of cognitive impairments across domains, with deficits in executive function/processing speed the most common isolated impairment. We also demonstrate that higher education was associated with a Minimal/No Impairment phenotype and lower risk for cognitive decline over time.

Spatial patterns of gray and white matter compromise relate to age of seizure onset in temporal lobe epilepsy.

OBJECTIVE: Temporal Lobe Epilepsy (TLE) is frequently a neurodevelopmental disorder, involving subcortical volume loss, cortical atrophy, and white matter (WM) disruption. However, few studies have addressed how these pathological changes in TLE relate to one another. In this study, we investigate spatial patterns of gray and white matter degeneration in TLE and evaluate the hypothesis that the relationship among these patterns varies as a function of the age at which seizures begin. METHODS: Eighty-two patients with TLE and 59 healthy controls were enrolled. T1-weighted images were used to obtain hippocampal volumes and cortical thickness estimates. Diffusion-weighted imaging was used to obtain fractional anisotropy (FA) and mean diffusivity (MD) of the superficial WM (SWM) and deep WM tracts. Analysis of covariance was used to examine patterns of WM and gray matter alterations in TLE relative to controls, controlling for age and sex. Sliding window correlations were then performed to examine the relationships between SWM degeneration, cortical thinning, and hippocampal atrophy across ages of seizure onset. RESULTS: Cortical thinning in TLE followed a widespread, bilateral pattern that was pronounced in posterior centroparietal regions, whereas SWM and deep WM loss occurred mostly in ipsilateral, temporolimbic regions compared to controls. Window correlations revealed a relationship between hippocampal volume loss and whole brain SWM disruption in patients who developed epilepsy during childhood. On the other hand, in patients with adult-onset TLE, co-occurring cortical and SWM alterations were observed in the medial temporal lobe ipsilateral to the seizure focus. SIGNIFICANCE: Our results suggest that although cortical, hippocampal and WM alterations appear spatially discordant at the group level, the relationship among these features depends on the age at which seizures begin. Whereas neurodevelopmental aspects of TLE may result in co-occurring WM and hippocampal degeneration near the epileptogenic zone, the onset of seizures in adulthood may set off a cascade of SWM microstructural loss and cortical atrophy of a neurodegenerative nature.

Dose-Dependent Atrophy in Bilateral Amygdalae and Nuclei After Brain Radiation Therapy and Its Association With Mood and Memory Outcomes on a Longitudinal Clinical Trial.

PURPOSE: Amygdalae are bilateral, almond-shaped structures located anterior to the hippocampi, critical to limbic system functions of emotional processing and memory consolidation. The amygdalae are heterogeneous, composed of multiple nuclei with distinct structural and functional properties. We prospectively assessed associations between longitudinal changes in amygdala morphometry, including component nuclei, and functional outcomes in patients with primary brain tumors receiving radiation therapy (RT). METHODS AND MATERIALS: On a prospective longitudinal trial, 63 patients underwent high-resolution volumetric brain magnetic resonance imaging and testing for mood (Beck Depression Inventory and Beck Anxiety Inventory), memory (Brief Visuospatial Memory Test-Revised [BVMT] Total Recall and Delayed Recall; Hopkins Verbal Learning Test-Revised [HVLT] Total Recall and Delayed Recall), and health-related quality-of-life outcomes (Functional Assessment of Cancer Therapy-Brain Social/Family Well-Being and Emotional Well-Being) at baseline and 3, 6, and 12 months after RT. Amygdalae, including 8 nuclei, were autosegmented bilaterally using validated techniques. Linear mixed-effects models assessed longitudinal change in amygdalae and nuclei volumes and associations with dose and outcomes. Wilcoxon rank sum tests compared amygdala volume change between patient groups with worse and more stable outcomes at each time point. RESULTS: Atrophy was found in the right amygdala at 6 months (P = .001) and the left amygdala at 12 months (P = .046). A higher dose was associated with atrophy of the left amygdala (P = .013) at 12 months. The right amygdala showed dose-dependent atrophy at 6 months (P = .016) and 12 months (P = .001). Worse BVMT-Total, HVLT-Total, and HVLT-Delayed performance was associated with smaller left lateral (P = .014, P = .004, and P = .007, respectively) and left basal (P = .034, P = .016, and P = .026, respectively) nuclei volumes. Increased anxiety at 6 months was associated with greater combined (P = .031) and right (P = .007) amygdala atrophy. Greater left amygdala atrophy (P = .038) was noted in patients with decreased emotional well-being at 12 months. CONCLUSIONS: Bilateral amygdalae and nuclei undergo time- and dose-dependent atrophy after brain RT. Atrophy in amygdalae and specific nuclei was associated with poorer memory, mood, and emotional well-being. Amygdalae-sparing treatment planning may preserve neurocognitive and neuropsychiatric outcomes in this population.

Preoperative white matter network organization and memory decline after epilepsy surgery.

OBJECTIVE: Risk for memory decline is a common concern for individuals with temporal lobe epilepsy (TLE) undergoing surgery. Global and local network abnormalities are well documented in TLE. However, it is less known whether network abnormalities predict postsurgical memory decline. The authors examined the role of preoperative global and local white matter network organization and risk of postoperative memory decline in TLE. METHODS: One hundred one individuals with TLE (n = 51 with left TLE and 50 with right TLE) underwent preoperative T1-weighted MRI, diffusion MRI, and neuropsychological memory testing in a prospective longitudinal study. Fifty-six age- and sex-matched controls completed the same protocol. Forty-four patients (22 with left TLE and 22 with right TLE) subsequently underwent temporal lobe surgery and postoperative memory testing. Preoperative structural connectomes were generated via diffusion tractography and analyzed using measures of global and local (i.e., medial temporal lobe [MTL]) network organization. Global metrics measured network integration and specialization. The local metric was calculated as an asymmetry of the mean local efficiency between the ipsilateral and contralateral MTLs (i.e., MTL network asymmetry). RESULTS: Higher preoperative global network integration and specialization were associated with higher preoperative verbal memory function in patients with left TLE. Higher preoperative global network integration and specialization, as well as greater leftward MTL network asymmetry, predicted greater postoperative verbal memory decline for patients with left TLE. No significant effects were observed in right TLE. Accounting for preoperative memory score and hippocampal volume asymmetry, MTL network asymmetry uniquely explained 25%-33% of the variance in verbal memory decline for left TLE and outperformed hippocampal volume asymmetry and global network metrics. MTL network asymmetry alone produced good diagnostic classification of memory decline in left TLE (i.e., an area under the receiver operating characteristic curve of 0.80-0.84 and correct classification of 65%-76% of cases with cross-validation). CONCLUSIONS: These preliminary data suggest that global white matter network disruption contributes to verbal memory impairment preoperatively and predicts postsurgical verbal memory outcomes in left TLE. However, a leftward asymmetry of MTL white matter network organization may confer the highest risk for verbal memory decline. Although this requires replication in a larger sample, the authors demonstrate the importance of characterizing preoperative local white matter network properties within the to-be-operated hemisphere and the reserve capacity of the contralateral MTL network, which may eventually be useful in presurgical planning.

Bilingualism and Structural Network Organization in Temporal Lobe Epilepsy: Resilience in Neurologic Disease.

BACKGROUND AND OBJECTIVES: There is growing evidence that bilingualism can induce neuroplasticity and modulate neural efficiency, resulting in greater resistance to neurologic disease. However, whether bilingualism is beneficial to neural health in the presence of epilepsy is unknown. We tested whether bilingual individuals with temporal lobe epilepsy (TLE) have improved whole-brain structural white matter network organization. METHODS: Healthy controls and individuals with TLE recruited from 2 specialized epilepsy centers completed diffusion-weighted MRI and neuropsychological testing as part of an observational cohort study. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory. Global analyses compared network integration (path length) and specialization (transitivity) in TLE vs controls and in a 2 (left vs right TLE) × 2 (bilingual vs monolingual) model. Local analyses compared mean local efficiency of predefined frontal-executive and language (i.e., perisylvian) subnetworks. Exploratory correlations examined associations between network organization and neuropsychological performance. RESULTS: A total of 29 bilingual and 88 monolingual individuals with TLE matched on several demographic and clinical variables and 81 age-matched healthy controls were included. Globally, a significant interaction between language status and side of seizure onset revealed higher network organization in bilinguals compared with monolinguals but only in left TLE (LTLE). Locally, bilinguals with LTLE showed higher efficiency in frontal-executive but not in perisylvian networks compared with LTLE monolinguals. Improved whole-brain network organization was associated with better executive function performance in bilingual but not monolingual LTLE. DISCUSSION: Higher white matter network organization in bilingual individuals with LTLE suggests a neuromodulatory effect of bilingualism on whole-brain connectivity in epilepsy, providing evidence for neural reserve. This may reflect attenuation of or compensation for epilepsy-related dysfunction of the left hemisphere, potentially driven by increased efficiency of frontal-executive networks that mediate dual-language control. This highlights a potential role of bilingualism as a protective factor in epilepsy, motivating further research across neurologic disorders to define mechanisms and develop interventions.

Establishing the cross-cultural applicability of a harmonized approach to cognitive diagnostics in epilepsy: Initial results of the International Classification of Cognitive Disorders in Epilepsy in a Spanish-speaking sample.

OBJECTIVE: This study was undertaken to evaluate the cross-cultural application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to a cohort of Spanish-speaking patients with temporal lobe epilepsy (TLE) living in the United States. METHODS: Eighty-four Spanish-speaking patients with TLE completed neuropsychological measures of memory, language, executive function, visuospatial functioning, and attention/processing speed as part of the Neuropsychological Screening Battery for Hispanics. The contribution of demographic and clinical variables to cognitive performance was evaluated. A sensitivity analysis was conducted by examining the base rates of impairment across several impairment thresholds. The IC-CoDE taxonomy was then applied, and the base rate of cognitive phenotypes for each cutoff was calculated. The distribution of phenotypes was compared to the published IC-CoDE taxonomy data, which utilized a large, multicenter cohort of English-speaking patients with TLE. RESULTS: Across the different impairment cutoffs, memory was the most impaired cognitive domain, with impairments in list learning ranging from 50% to 78%. Application of the IC-CoDE taxonomy utilizing a -1.5-SD cutoff revealed an intact cognitive profile in 47.6% of patients, single-domain impairment in 23.8% of patients, bidomain impairment in 14.3% of patients, and generalized impairment in 14.3% of the sample. This distribution was comparable to the phenotype distribution observed in the IC-CoDE validation sample. SIGNIFICANCE: We demonstrate a similar pattern and distribution of cognitive phenotypes in a Spanish-speaking epilepsy cohort compared to an English-speaking sample. This suggests stability in the underlying phenotypes associated with TLE and applicability of the IC-CoDE for guiding cognitive diagnostics in epilepsy research that can be applied to culturally and linguistically diverse samples.

White matter network organization predicts memory decline after epilepsy surgery.

The authors have withdrawn their manuscript owing to a substantial change in data analysis and findings/conclusions. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Development and application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Initial results from a multi-center study of adults with temporal lobe epilepsy.

[Correction Notice: An Erratum for this article was reported online in Neuropsychology on Sep 15 2022 (see record 2023-01997-001). In the original article, there was an error in Figure 2. In the box at the top left of the figure, the fourth explanation incorrectly stated, "Generalized impairment = At least one test < -1.0 or -1.5SD in three or more domains." The correct wording is "Generalized impairment = At least two tests < -1.0 or -1.5SD in each of three or more domains." All versions of this article have been corrected.] Objective: To describe the development and application of a consensus-based, empirically driven approach to cognitive diagnostics in epilepsy research-The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) and to assess the ability of the IC-CoDE to produce definable and stable cognitive phenotypes in a large, multi-center temporal lobe epilepsy (TLE) patient sample. METHOD: Neuropsychological data were available for a diverse cohort of 2,485 patients with TLE across seven epilepsy centers. Patterns of impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) using two impairment thresholds (≤1.0 and ≤1.5 standard deviations below the normative mean). Cognitive phenotypes were derived across samples using the IC-CoDE and compared to distributions of phenotypes reported in existing studies. RESULTS: Impairment rates were highest on tests of language, followed by memory, executive functioning, attention/processing speed, and visuospatial ability. Application of the IC-CoDE using varying operational definitions of impairment (≤ 1.0 and ≤ 1.5 SD) produced cognitive phenotypes with the following distribution: cognitively intact (30%-50%), single-domain (26%-29%), bi-domain (14%-19%), and generalized (10%-22%) impairment. Application of the ≤ 1.5 cutoff produced a distribution of phenotypes that was consistent across cohorts and approximated the distribution produced using data-driven approaches in prior studies. CONCLUSIONS: The IC-CoDE is the first iteration of a classification system for harmonizing cognitive diagnostics in epilepsy research that can be applied across neuropsychological tests and TLE cohorts. This proof-of-principle study in TLE offers a promising path for enhancing research collaborations globally and accelerating scientific discoveries in epilepsy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Moving towards a taxonomy of cognitive impairments in epilepsy: application of latent profile analysis to 1178 patients with temporal lobe epilepsy.

In efforts to understand the cognitive heterogeneity within and across epilepsy syndromes, cognitive phenotyping has been proposed as a new taxonomy aimed at developing a harmonized approach to cognitive classification in epilepsy. Data- and clinically driven approaches have been previously used with variability in the phenotypes derived across studies. In our study, we utilize latent profile analysis to test several models of phenotypes in a large multicentre sample of patients with temporal lobe epilepsy and evaluate their demographic and clinical profiles. For the first time, we examine the added value of replacing missing data and examine factors that may be contributing to missingness. A sample of 1178 participants met the inclusion criteria for the study, which included a diagnosis of temporal lobe epilepsy and the availability of comprehensive neuropsychological data. Models with two to five classes were examined using latent profile analysis and the optimal model was selected based on fit indices, posterior probabilities and proportion of sample sizes. The models were also examined with imputed data to investigate the impact of missing data on model selection. Based on the fit indices, posterior probability and distinctiveness of the latent classes, a three-class solution was the optimal solution. This three-class solution comprised a group of patients with multidomain impairments, a group with impairments predominantly in language and a group with no impairments. Overall, the multidomain group demonstrated a worse clinical profile and comprised a greater proportion of patients with mesial temporal sclerosis, a longer disease duration and a higher number of anti-seizure medications. The four-class and five-class solutions demonstrated the lowest probabilities of a group membership. Analyses with imputed data demonstrated that the four-class solution was the optimal solution; however, there was a weak agreement between the missing and imputed data sets for the four-Class solutions (κ = 0.288, P < 0.001). This study represents the first to use latent profile analysis to test and compare multiple models of cognitive phenotypes in temporal lobe epilepsy and to determine the impact of missing data on model fit. We found that the three-phenotype model was the most meaningful based on several fit indices and produced phenotypes with unique demographic and clinical profiles. Our findings demonstrate that latent profile analysis is a rigorous method to identify phenotypes in large, heterogeneous epilepsy samples. Furthermore, this study highlights the importance of examining the impact of missing data in phenotyping methods. Our latent profile analysis-derived phenotypes can inform future studies aimed at identifying cognitive phenotypes in other neurological disorders.

Local molecular and global connectomic contributions to cross-disorder cortical abnormalities.

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21,000 participants and N = 26,000 controls, collected using a harmonised processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find a relationship between molecular vulnerability and white-matter architecture that drives cortical disorder profiles. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, inferior temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local molecular attributes and global connectivity jointly shape cross-disorder cortical abnormalities.

Artificial Intelligence Applications in the Imaging of Epilepsy and Its Comorbidities: Present and Future.

Artificial intelligence (AI) is increasingly used in medical image analysis and has accelerated scientific discoveries across fields of medicine. In this review, we highlight how AI has been applied to neuroimaging in patients with epilepsy to enhance classification of clinical diagnosis, prediction of treatment outcomes, and the understanding of cognitive comorbidities. We outline the strengths and shortcomings of current AI research and the need for future studies using large datasets that test the reproducibility and generalizability of current findings, as well as studies that test the clinical utility of AI approaches.

Cognitive phenotypes in frontal lobe epilepsy.

OBJECTIVE: Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. METHOD: One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. RESULTS: Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. SIGNIFICANCE: This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.

Can bilingualism increase neuroplasticity of language networks in epilepsy?

Individuals with left temporal lobe epilepsy (TLE) have a higher rate of atypical (i.e., bilateral or right hemisphere) language lateralization compared to healthy controls. In addition, bilinguals have been observed to have a less left-lateralized pattern of language representation. We examined the combined influence of bilingual language experience and side of seizure focus on language lateralization profiles in TLE to determine whether bilingualism promotes re-organization of language networks. Seventy-two monolingual speakers of English (21 left TLE; LTLE, 22 right TLE; RTLE, 29 age-matched healthy controls; HC) and 24 English-dominant bilinguals (6 LTLE, 7 RTLE, 11 HC) completed a lexical-semantic functional MRI task and standardized measures of language in English. Language lateralization was determined using laterality indices based on activations in left vs right homologous perisylvian regions-of-interest (ROIs). In a fronto-temporal ROI, LTLE showed the expected pattern of weaker left language lateralization relative to HC, and monolinguals showed a trend of weaker left language lateralization relative to bilinguals. Importantly, these effects were qualified by a significant group by language status interaction, revealing that bilinguals with LTLE had greater rightward language lateralization relative to monolingual LTLE, with a large effect size particularly in the lateral temporal region. Rightward language lateralization was associated with better language scores in bilingual LTLE. These preliminary findings suggest a combined effect of bilingual language experience and a left hemisphere neurologic insult, which may together increase the likelihood of language re-organization to the right hemisphere. Our data underscore the need to consider bilingualism as an important factor contributing to language laterality in patients with TLE. Bilingualism may be neuroprotective pre-surgically and may mitigate post-surgical language decline following left anterior temporal lobectomy, which will be important to test in larger samples.

Neurobehavioral and Clinical Comorbidities in Epilepsy: The Role of White Matter Network Disruption.

Epilepsy is a common neurological disorder associated with alterations in cortical and subcortical brain networks. Despite a historical focus on gray matter regions involved in seizure generation and propagation, the role of white matter (WM) network disruption in epilepsy and its comorbidities has sparked recent attention. In this review, we describe patterns of WM alterations observed in focal and generalized epilepsy syndromes and highlight studies linking WM disruption to cognitive and psychiatric comorbidities, drug resistance, and poor surgical outcomes. Both tract-based and connectome-based approaches implicate the importance of extratemporal and temporo-limbic WM disconnection across a range of comorbidities, and an evolving literature reveals the utility of WM patterns for predicting outcomes following epilepsy surgery. We encourage new research employing advanced analytic techniques (e.g., machine learning) that will further shape our understanding of epilepsy as a network disorder and guide individualized treatment decisions. We also address the need for research that examines how neuromodulation and other treatments (e.g., laser ablation) affect WM networks, as well as research that leverages larger and more diverse samples, longitudinal designs, and improved magnetic resonance imaging acquisitions. These steps will be critical to ensuring generalizability of current research and determining the extent to which neuroplasticity within WM networks can influence patient outcomes.