Mapping memory function in temporal lobe epilepsy (TLE) is important for understanding surgical risk, yet practical noninvasive tools remain limited. We tested whether a face-name associative memory fMRI task could detect subregional dysfunction within the amygdala-hippocampal complex (AHC) in TLE. Forty-nine individuals with unilateral TLE (29 left-, 20 right-onset; 51% MTS-negative) and 25 controls from three centers were scanned during a face-name encoding task and completed delayed recognition and neuropsychological tests of memory. The hippocampal head, body, tail, and amygdala were anatomically segmented, and activation was examined for encoding and novelty contrasts. In controls, AHC activation was predominantly right-lateralized. For encoding, a Region × Hemisphere × Group interaction showed reduced ipsilateral amygdala and hippocampal tail activation in right TLE, with relative preservation in other subregions. Left TLE showed a nonsignificant medium effect in the ipsilateral amygdala. In right TLE, greater contralateral amygdala activation correlated with better face-name recognition and verbal memory, while greater ipsilateral hippocampal tail activation correlated with better verbal and visual memory. Findings were independent of mesial temporal sclerosis and hippocampal volume. A brief, ecologically valid face-name fMRI task revealed lateralized, subregion-specific disruption in right TLE and behaviorally relevant variability in the amygdala and posterior hippocampal engagement. Future work is needed to determine whether these activation patterns predict post-surgical memory outcomes.

BACKGROUND:The hippocampus comprises discrete anatomic subfields subserving different components of memory. We evaluated longitudinal, dose-dependent volumetric changes in hippocampal subfields after fractionated RT and determined their associations with verbal and visuospatial memory performance. METHODS:Eighty-nine adults with primary brain tumors received fractionated RT on a prospective clinical trial. High-resolution 3D volumetric MRI and memory tests were obtained at baseline and 3, 6, and 12-months post-RT. Bilateral hippocampi and their thirty-eight subfields were segmented using robust automated parcellation. Linear mixed-effects (LME) models analyzed (1) time-dependent atrophy, (2) dose-volume relationships, and (3) subfield-memory associations at the same timepoint, corrected for multiple comparisons. RESULTS:Multiple left and right-sided hippocampal subfields demonstrated significant atrophy at 3, 6, and 12-months post-RT (all p ≤ 0.05). Dose-dependent atrophy was significant at 12 months (p = .01) in the left hippocampus and across all time points in the right (all p ≤ 0.05). Eight right-sided and one left-sided subfield exhibited dose-dependent atrophy across all time points (all p ≤ 0.05). Greater left hippocampal tail and molecular layer volumes were associated with higher verbal memory scores, while greater volumes of multiple right-sided subfields predicted better visuospatial memory performance (all p ≤ 0.05, 𝛽 > 0). CONCLUSIONS:Fractionated RT induces progressive, dose-related atrophy in discrete hippocampal subfields, with earlier and steeper dose-response curves in right-sided subfields. Higher volumes within multiple left and right-sided subfields were associated with better verbal and visuospatial memory, respectively. Subfield-sparing planning objectives may optimize cognitive outcomes in primary brain tumor patients when hippocampal avoidance is not feasible.

IntroductionAdvanced cognitive aging remains a major concern for people living with HIV (PWH), even in the context of viral suppression. This underscores the need for sensitive tools that can detect subtle cognitive change. Mobile cognitive assessments offer a scalable and ecologically valid approach, yet their sensitivity to longitudinal change in clinical populations is not well established.MethodsWe examined longitudinal performance and predictors of change on a 14-day mobile Verbal Learning Test (mVLT) administered remotely at baseline and again 12–46 months (M = 26.7) later in 24 PWH and 13 HIV-negative controls aged 51–74, and compared these trajectories with change on standard in-person neuropsychological testing.ResultsAggregate mean mVLT performance improved over time among controls, but this was not evident among PWH (i.e., a significant group X time interaction). In contrast, longitudinal trajectories did not differ by group on the standard in-person Hopkins Verbal Learning Test-Revised, suggesting greater sensitivity of the mobile measure in this sample. Age moderated mVLT trajectories, such that increasing age was associated with worse longitudinal trajectories in PWH, whereas age was unrelated to change in controls. Among PWH, worse mVLT trajectories were associated with higher cerebrovascular risk, lower social functioning, and poorer baseline global learning performance, but not depressive symptoms, HIV disease markers, or other medical comorbidities.DiscussionThese preliminary findings suggest that the mVLT captures group-level differences in longitudinal learning trajectories and heterogeneity in performance over time among PWH, in line with contemporary models of cognitive aging in HIV. With replication in larger samples, mobile assessments could support scalable monitoring of cognitive function in PWH.

Background and Objectives:Older adults with epilepsy are at increased risk for Alzheimer's disease (AD), yet the mechanisms underlying this association remain poorly understood. We applied a validated AD neuroimaging signature to older adults with epilepsy to examine 1) whether older adults with epilepsy mirror AD-related changes, 2) associations with clinical, cognitive, and plasma biomarker outcomes, and 3) utility for identifying subgroups at heightened risk for cognitive decline. Our multicenter, prospectively enrolled cohort allowed for direct examination of differences in AD signatures between those with early-onset and late-onset unexplained epilepsy. Methods:Participants included 449 older adults: 87 with focal epilepsy from the multicenter Brain Aging and Cognition in Epilepsy (BrACE) cohort (age=66.10 [SD=6.86], including early-onset (<55 years at seizure onset) and late-onset (≥55 years at seizure onset) epilepsy); 362 from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU) healthy controls and individuals with mild cognitive impairment (MCI) or AD dementia. An AD signature was derived from regional cortical thickness and hippocampal volume weighted by their sensitivity to AD-related neurodegeneration in prior work. Associations between the AD signature, epilepsy characteristics, plasma biomarkers (β-amyloid 42/40, phosphorylated tau [pTau217, pTau181], neurofilament light chain [NfL]), and cognition were evaluated in BrACE. Results:Participants with epilepsy demonstrated more AD-like signatures compared to ADNI CU controls (β= -0.43, p adj <0.001), reflecting reduced thickness/volume in AD-vulnerable regions. This effect was stronger among early-onset (β= -0.57) versus late-onset (β= -0.26) epilepsy. In BrACE, the AD signature correlated with NfL (β= -0.30, p adj =0.050), memory performance (β= 0.30, p adj =0.006), and predicted greater odds of cognitive impairment specifically among those with early-onset, but not late-onset, epilepsy (interaction p adj =0.043). Further, among those with early-onset epilepsy, the AD signature significantly improved identification of cognitive impairment over and beyond the effects of plasma AD biomarkers ( p =0.041). Findings were similar when examining the effects of epilepsy duration rather than epilepsy onset age. Discussion:AD neuroimaging signatures may help identify clinically meaningful subgroups among older adults with epilepsy, particularly when integrated with AD biomarkers. Findings support a multimodal framework for assessing AD-related risk in epilepsy and highlight interactive effects of epilepsy chronicity and AD-related processes that can influence cognitive outcomes.

OBJECTIVE:Instrumental activities of daily living (IADLs) represent a critical but understudied measure of day-to-day function in people with epilepsy (PWE). In the multicenter Brain Aging and Cognition in Epilepsy (BrACE) study of PWE ≥55 years of age, we examined the proportion, clinical correlates, epilepsy-related predictors, and longitudinal trajectory of IADL impairment. METHODS:IADLs were assessed using the Functional Activities Questionnaire (FAQ; range = 0-30; higher = more impaired); FAQ ≥ 2 defines mild cognitive impairment (MCI)-level impairment and FAQ ≥ 5 dementia-level functional impairment. Multivariable Firth penalized logistic regression identified factors associated with baseline functional impairment. Global cognition (Montreal Cognitive Assessment [MoCA]), individual cognitive measures, and quality of life (QOL) were compared between the impaired and unimpaired groups. Exploratory linear regression evaluated factors associated with longitudinal functional decline. RESULTS:Of 57 participants (mean age ± SD = 66.6 ± 7.2 years; female = 52.6%), 38.6% (n = 22) had MCI-level functional impairment and 17.5% (n = 10) had dementia-level functional impairment. In univariate analyses, worse FAQ scores were associated with lower education, higher area-deprivation index, early-onset epilepsy (EOE; <60 years), anti-seizure medication polytherapy, and epilepsy localization (all p's < .05). In multivariable analysis, temporal lobe epilepsy (odds ratio [OR] = 3.73, 95% confidence interval [CI] = 1.02-16.12, p = .047), EOE (OR = 6.91, 95% CI = 1.36-46.37, p = .019), and lower education (OR = 0.69, 95% CI = 0.51-0.90,p = .004) remained independently associated with baseline MCI-level functional impairment. Lower education (OR = 0.62, 95% CI = 0.37-0.87, p = .004) was the only factor associated with dementia-level IADL impairment. IADL-impaired participants demonstrated lower verbal memory scores (adjusted-p = .042) and MoCA (adjusted-p = .006), particularly in visuospatial/executive function, attention, and memory subscores, and worse QOL (adjusted-p = .042). IADL impairment was greatest in financially-mediated and memory-dependent tasks. Longitudinally, EOE (p = .017) and older age (p = .012) were associated with greater functional decline. Four of 13 participants (approximately one-third) progressed to significantly worse function over a 2-year period, with two (15.4%) progressing from MCI-level to dementia-level impairment and two (15.4%) from normal function to MCI-level IADL impairment. SIGNIFICANCE:Functional impairment affects ~40% of older PWE, with ~1-in-6 experiencing functional impairment comparable to overt dementias. Temporal lobe localization, EOE, lower education, and poorer cognition are important determinants of baseline functional status. Exploratory longitudinal analyses has suggested that EOE and older age were associated with accelerated functional decline, although these findings require confirmation in larger cohorts. These findings provide one of the first epilepsy-specific characterizations of IADL impairment and support routine functional assessment in PWE.

BACKGROUND:In the presence of neurological insult, how language and memory networks jointly reorganise provides insights into mechanisms of neuroplasticity and can inform presurgical planning. As (re)organisation is often studied within a single cognitive modality, how language and memory interact during (re)organisation in response to epilepsy and the implications for memory outcomes is less clear. We investigated (1) the rates and patterns of joint (re)organisation and (2) their associations with pre- and postsurgical memory function. METHODS:Individuals with epilepsy (n=162) from three neurosurgical centres underwent the Wada procedure. We examined colateralisation patterns (ie, concordance/discordance) between language and both global and verbal memory (n=34), and associations with clinical characteristics and preoperative and postoperative memory outcomes. RESULTS:Overall concordance between language and memory colateralisation was minimal-to-weak across both global memory and verbal memory (kappa=0.28-0.44). Discordance was primarily observed in individuals with left-lateralised language, of whom 52% and 32% showed discordance in global and verbal memory, respectively. Discordance was most pronounced in left hemisphere epilepsy and mesial temporal sclerosis. Conversely, right-lateralised language consistently predicted right-lateralised memory (95%-100%), regardless of seizure laterality or memory type. While discordance was not associated with presurgical memory function, discordance predicted superior postsurgical memory outcomes following surgery in the language-dominant hemisphere (p<0.05; ηp 2=0.30). CONCLUSIONS:When language dominance is atypical, memory tends to colateralise. However, when language remains typical, concordance with memory is weak, particularly for left hemisphere seizure onset. An interhemispheric shift in language may trigger a shift in memory, possibly to maintain efficient communication between medial temporal and neocortical language networks. In contrast, memory appears able to reorganise in isolation, with discordance predicting better postsurgical memory outcomes without detriment to presurgical function. Our findings support the continued need for separate presurgical mapping of language and memory lateralisation, particularly in the case of typical language dominance and left hemisphere seizures.

BACKGROUND:Limbic white matter (WM) of the Papez circuit, including the fornix, dorsal cingulum, and parahippocampal cingulum (PHC), interplay with the hippocampus as key components of the memory network. We analyzed biomarkers of injury to these pathways to understand their impact on post-radiation therapy (RT) memory performance. METHODS:Primary brain tumor patients on a prospective trial receiving fractionated brain RT (n = 57) underwent volumetric MRI, diffusion tensor imaging, and memory assessments (Hopkins Verbal Learning Test-Revised [HVLT-R] Total and Delayed Recall and Brief Visuospatial Memory Test -Revised [BVMT-R] Total and Delayed Recall) at baseline and 3, 6, and 12 months post-RT. MRI biomarkers included volume, fractional anisotropy (FA), and mean diffusivity (MD). Linear mixed-effects models assessed associations between biomarkers and memory performance over time. RESULTS:Smaller volumes in the right fornix were associated with lower BVMT-R-Total scores (P = 0.019) and left PHC volume loss was associated with worse performance on BVMT-R-Delayed (P = 0.039). Lower FA in the left (P = 0.010) and right (P = 0.019) fornix was associated with lower BVMT-R-Total performance. Lower FA in the left dorsal cingulum (P = 0.038) and right PHC (P = 0.039) were associated with lower HVLT-R-Total and HVLT-R-Delayed scores, respectively. Higher MD in bilateral fornix (P = 0.01) and right PHC (P = 0.011) correlated with lower BVMT-R-Total scores; higher MD in the right PHC (P = 0.046) also correlated with lower HVLT-R-Total scores. Hippocampal volume was not associated with memory scores. CONCLUSION:Poorer microstructural integrity in limbic WM tracts of the Papez circuit predicted worse memory performance, while hippocampal injury did not. Dose avoidance in these tracts may preserve memory outcomes.

Purpose This study investigated patterns of cortical atrophy longitudinally in a prospective cohort of well-characterized patients with primary brain tumors before radiation therapy (RT) and at discrete time points up to 1-year post-RT. Patients with more impaired profiles were hypothesized to show greater and more widespread atrophy post-RT than patients with minimally impaired profiles. Methods and Materials Adults (aged 20-72 years) with primary brain tumors were enrolled in a prospective, observational study examining the effects of fractionated, partial brain RT on brain structure and cognition (n = 85). Cortical atrophy rates were compared using multilevel modeling across 4 different time points (baseline, 3, 6, and 12 months after RT) between minimal, generalized, and isolated verbal memory impairment phenotypes taken from a previous study's latent profile analysis. Results The minimal impairment phenotype showed no regions of significant change in cortical thickness across the 4 time points analyzed. The generalized impairment phenotype showed bihemispheric, multilobar cortical atrophy, with the greatest changes observed in the left precentral gyrus, lateral occipital cortex, and frontal pole. The verbal memory impairment phenotype demonstrated less extensive atrophy focally in the left superior temporal and superior parietal cortices. Annualized atrophy rates in regions of significant cortical thinning in the generalized and verbal memory impairment phenotypes ranged from 3.5% to 8.7% compared with baseline. Conclusions In patients with primary brain tumors, the cognitive profile before RT informs the pattern and risk for RT-related cortical atrophy. Cognitive profiles may aid in identifying patients at greater risk for RT-related atrophy and accelerated cognitive decline.

Are bilingual language networks flexible enough to dynamically adapt to neurological insult? We examined language lateralization in 24 bilingual and 46 monolingual adults with temporal lobe epilepsy using functional MRI. In a group of primarily early sequential bilingual patients, the first acquired language (L1) showed more bilateral lateralization than in monolingual patients, with no effect of seizure onset laterality. In contrast, the second-acquired language (L2) was more bilateral in the presence of left hemisphere epilepsy and more left-lateralized in right hemisphere epilepsy. Most notably, in left hemisphere epilepsy, seizure onset closer to L2 acquisition was associated with more right-lateralized L2 representation. These findings suggest a compensatory process in which L2 networks strengthen in the hemisphere opposite the seizure focus, potentially reflecting neural adaptation in early bilingualism. Conversely, L1 appears to have less dynamic reorganization in response to neurological insult. Together, these findings highlight the importance of timing in both language experience and neurological stress in shaping language network organization. They support the view that the bilingual brain is not simply the sum of two monolingual systems, but a dynamic and unique system marked by high interindividual variability, in which divergence between languages may emerge under certain experience- and context-dependent conditions.

OBJECTIVE:Naming and verbal memory are key components of epilepsy evaluations, as impairments often reflect left temporal dysfunction, and baseline performance helps estimate postsurgical risk. The utility of naming tests in bilingual individuals with epilepsy, however, has been questioned. We examined whether naming and verbal memory performance reflects seizure laterality in bilingual adults, how bilingualism affects baseline scores, and whether bilingual factors moderate the effects of seizure laterality on cognition. METHODS:We analyzed naming and verbal memory data from 148 monolingual and 63 bilingual adults with unilateral epilepsy across two centers. Participants completed English-based tests of visual naming, story recall, and word-list recall. Analyses of covariance and Bayesian models tested effects of seizure laterality, bilingual status, and their interaction. Regressions tested the moderating effects of bilingual factors (e.g., age at acquisition, proficiency, English immersion). RESULTS:Bilinguals scored lower on naming than monolinguals, but both groups showed worse naming in left versus right hemisphere epilepsy (nonsignificant interaction). Using monolingual norms, naming impairment was far more frequent in bilinguals (90%-92% left onset, 63%-71% right onset) than monolinguals, but rates normalized after adjusting for the bilingual naming disadvantage. Among non-US-born bilinguals, greater immersion was associated with better naming in right-but not left-hemisphere epilepsy. For verbal memory, seizure laterality effects were present in story recall, and in word-list recall among patients with mesial temporal sclerosis, but did not differ by bilingual status. SIGNIFICANCE:Naming and verbal memory remain reliable markers of seizure laterality in bilingual adults with epilepsy. For naming, however, improved measures and bilingual-specific norms are essential to avoid misclassification and support accurate clinical decision-making.

Background. Patients with brain tumors demonstrate heterogeneous patterns of cognitive impairment, likely related to multifactorial etiologies and variable tumor-specific factors. Cognitive phenotyping offers a patient-centered approach to parsing heterogeneity by classifying individuals based on patterns of impairment. The aim of this study was to investigate the neuroanatomical patterns associated with each phenotype to gain a better understanding of the mechanisms underlying impairments. Methods. Patients with primary brain tumors were recruited for a prospective, observational study. Patients were cognitively phenotyped using latent profile analysis in a prior study, revealing 3 distinct groups: generalized, isolated verbal memory, and minimal impairment. Whole brain cortical thickness (CT), fractional anisotropy, and mean diffusivity (MD) were compared across phenotypes, and associations between imaging metrics and cognitive scores were explored. Results. Neurocognitive, structural MRI, and diffusion MRI data were available for 82 participants at baseline. Compared to the minimal impairment group, the generalized impairment group showed a widespread, bi-hemispheric pattern of decreased CT (P-value range: .004-.049), while the verbal memory impairment group showed decreased CT (P-value range: .006-.049) and increased MD (P-value range: .015-.045) bilaterally in the temporal lobes. In the verbal memory impairment group only, increased parahippocampal MD was associated with lower verbal memory scores (P-values < .01). Conclusions. Cognitive phenotypes in patients with brain tumors showed unique patterns of brain pathology, suggesting different underlying mechanisms of their impairment profiles. These distinct patterns highlight the biological relevance of our phenotyping approach and help to identify areas of structural and microstructural vulnerability that could inform treatment decisions.

Purpose/Objective(s) Radiation therapy (RT) is critical for primary brain tumors, yet many patients will experience neurocognitive decline. Bilateral hippocampi are largely implicated, with relative sparing of these areas as a cognitive protective strategy with whole brain. We have previously described that dose-dependent atrophy is found in the hippocampus (HC), yet just as the brain is a complex and interconnected organ the HC itself has many subfields which subserve different components of memory. Here, we examine changes in hippocampal subfield volume after RT, in relation to dose and time from treatment, as well as the association between these changes and decline in verbal and visuospatial memory. Materials/Methods Data were analyzed from a prospective longitudinal clinical trial. Patients (n = 85) with primary brain tumors receiving fractionated RT completed high-resolution volumetric brain MRI and neurocognitive evaluation at baseline and 3-, 6-, and 12-month intervals. Image processing using robust, validated automated parcellation segmented the bilateral HC and the following subfields: parasubiculum, presubiculum, subiculum, corpu ammonis (CA) 1-4, granule and molecular cell layers of the dentate gyrus (GC-ML-DG), hippocampal-amygdala transition area (HATA), fimbria, molecular layer, HC fissure, and HC tail. Neurocognitive testing was performed by certified neuropsychologists and included the Brief Visuospatial Memory Test (BVMT) and Hopkins Verbal Learning Test (HVLT). Multivariable linear mixed-effects models assessed longitudinal changes in whole HC (left, right) and nuclei volumes as well as associations between dose, volume, and verbal and visuospatial memory performance. Results We found significant atrophy in the left HC at 6 months (P = 0.032). Atrophy was dose-dependent in the left HC at 12 months (P = 0.025), and the right HC at 3 months (P = 0.018), 6 months (P = 0.016) and 12 months (P = 0.009). Worse verbal memory on the HVLT total and delayed recall was associated with decreased volume in the left hippocampal tail (P = 0.0098 and P = 0.0090, respectively) and left hippocampus–amygdaloid transitional area (P = 0.013 and P = 0.026, respectively). Poor BVMT total recall was associated with atrophy of the right body of the subiculum (P = 0.024), right head of the presubiculum (P = 0.045), right body of the molecular layer (P = 0.031), and right parasubiculum (P = 0.024). Atrophy of the left hippocampal tail (P = 0.0044) was associated with poor BVMT delayed recall. Conclusion Significant overall atrophy was only noted in the left hippocampus at 6 months; however, dose-dependent atrophy was found in the bilateral hippocampi. Decrease in verbal and visuospatial memory was generally associated with left-sided hippocampal subfield atrophy, while decrease in visuospatial memory was associated with right-sided hippocampal subfield atrophy. Relative specificity of the HC subfields may allow more directed memory-preserving cognitive sparing strategies.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Physical exercise is an emerging target for improving cognition in aging and neurological disease. Due to the beneficial impact of exercise on hippocampal health and the vulnerability of the hippocampus in medication- resistant temporal lobe epilepsy (TLE), exercise could present a promising intervention in TLE. We investigated whether exercise engagement is associated with verbal memory function and hippocampal integrity in 29 young to middle-aged adults with refractory TLE and 21 demographically matched controls. Participants completed a self-reported questionnaire of weekly exercise, three tests of verbal memory, and a subset (n = 44) underwent structural MRI. Individuals with TLE self-reported lower exercise scores than controls across all levels of exercise intensity (p < 0.001). In TLE, greater exercise engagement was associated with better verbal memory (word-list recall and associative learning; rho = 0.46-0.47; p s FDR < 0.05), and with larger contralateral hippocampal volumes ( rho = 0.61; p < 0.01). These effects remained significant when controlling for epilepsy- related and demographic factors. Within the limitations of a cross-sectional observational study, these findings suggest that exercise may be a cognitive reserve factor in TLE, potentially mitigating memory decline by enhancing contralateral hippocampal integrity. With future replication and longitudinal studies to clarify the causal pathways of these relationships, exercise holds promise as a low-cost, accessible, and modifiable lifestyle target for improving cognitive health in individuals with refractory TLE.

Proper names are especially prone to retrieval failures and tip-of-the-tongue states (TOTs)-a phenomenon wherein a person has a strong feeling of knowing a word but cannot retrieve it. Current research provides mixed evidence regarding whether related names facilitate or compete with target-name retrieval. We examined this question in two experiments using a novel paradigm where participants either read a prime name aloud (Experiment 1) or classified a written prime name as famous or non-famous (Experiment 2) prior to naming a celebrity picture. Successful retrievals decreased with increasing trial number (and was dependent on the number of previously presented similar famous people) in both experiments, revealing a form of accumulating interference between multiple famous names. However, trial number had no effect on TOTs, and within each trial famous prime names increased TOTs only in Experiment 2. These results can be explained within a framework that assumes competition for selection at the point of lexical retrieval, such that successful retrievals decrease after successive retrievals of proper names of depicted faces of semantically similar people. By contrast, the effects of written prime words only occur when prime names are sufficiently processed, and do not provide evidence for competition but may reflect improved retrieval relative to a "don't know" response.

OBJECTIVE:Efforts to understand the global variability in cognitive profiles in patients with epilepsy have been stymied by the lack of a standardized diagnostic system. This study examined the cross-cultural applicability of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) in a cohort of patients with temporal lobe epilepsy (TLE) in India that was diverse in language, education, and cultural background. METHODS:A cohort of 548 adults with TLE from Mumbai completed a presurgical comprehensive neuropsychological evaluation. The IC-CoDE taxonomy was applied to derive cognitive phenotypes in the sample. Analyses of variance were conducted to examine differences in demographic and clinical characteristics across the phenotypes, and chi-squared tests were used to determine whether the phenotype distribution differed between the Mumbai sample and published data from a multicenter US sample. RESULTS:Using the IC-CoDE criteria, 47% of our cohort showed an intact cognitive profile, 31% a single-domain impairment, 16% a bidomain impairment, and 6% a generalized impairment profile. The distribution of cognitive phenotypes was similar between the Indian and US cohorts for the intact and bidomain phenotypes, but differed for the single and generalized domains. There was a larger proportion of patients with single-domain impairment in the Indian cohort and a larger proportion with generalized impairment in the US cohort. Among patients with single-domain impairment, a greater proportion exhibited memory impairment in the Indian cohort, whereas a greater proportion showed language impairment in the US sample, likely reflecting differences in language administration procedures and sample characteristics including a higher rate of mesial temporal sclerosis in the Indian sample. SIGNIFICANCE:Our results demonstrate the applicability of IC-CoDE in a group of culturally and linguistically diverse patients from India. This approach enhances our understanding of cognitive variability across cultures and enables harmonized and inclusive research into the neuropsychological aspects of epilepsy.

Background. Patients with primary brain tumors demonstrate heterogeneous patterns of cognitive dysfunction, which we explore using latent profile analysis to identify cognitive phenotypes and their trajectories in patients receiving radiotherapy (RT). Methods. Ninety-six patients completed neuropsychological testing before and post-RT (3, 6, and 12 months) on a prospective longitudinal trial, including measures of processing speed, executive function, language, and verbal and visual memory. Models with 2-4 classes were examined. Demographic and clinical data were examined across phenotypes and post-RT cognitive change was evaluated. Results. The optimal model identified 3 unique cognitive phenotypes including a group of patients with generalized impairments (11.5%), a group with isolated verbal memory impairments (21.9%), and a group with minimal impairments (66.7%). The Verbal Memory phenotype had fewer years of education (P = .007) and a greater proportion of males (P < .001); the Generalized group had a greater proportion of patients with IDH-wild type gliomas and showed greater symptoms of anxiety and poorer quality of life (P-values < .05); and the Minimal Impairment phenotype had higher rates of IDH-Mutant gliomas. Approximately 50% of patients declined on at least one cognitive domain with memory being the most vulnerable. Patients who declined reported greater symptoms of depression (P = .007) and poorer quality of life (P = .025). Conclusions. We identified 3 distinct cognitive phenotypes in patients with primary brain tumors receiving RT, each associated with unique demographic and clinical (eg, IDH mutational status) profiles, with mood symptoms associated with late cognitive decline. This patient-centered approach enhances our understanding of clinical profiles associated with cognitive dysfunction and treatment-related neurotoxicity.

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.

Beyond the hippocampus, there are no evidence-based dose constraints for eloquent brain structures which subserve cognitive domains. We performed a multivariate NTCP analysis of post-RT neurocognitive decline, examining dosimetric predictors of eloquent brain regions in a prospective longitudinal clinical trial. 83 patients with primary brain tumors receiving fractionated RT completed comprehensive neurocognitive evaluation and high-resolution volumetric and diffusion MRI at baseline and 6 months post-RT. Image processing using robust, validated automated segmentation parcellated individual white matter (WM) tracts, cortical regions, and hippocampi. Well-validated neurocognitive tests evaluating multiple cognitive domains were assessed with negative reliable change indices adjusted for practice effects between timepoints scored as decline. Univariate logistic regression and multivariate model building were performed examining dose to eloquent structures and clinical variables. Univariate analysis showed mean dose to the bilateral caudal anterior cingulate cortex and WM were correlated with decline in executive function. Attention/processing speed decline was correlated with mean/max dose to the posterior corpus callosum (CC), volume getting >20 Gy in the combined CC, as well as anti-epileptic use and chemotherapy. On multivariate analysis for attention automated bootstrapped logistic regression performance at nested cross-validation by AUC was 0.59 (0.54-0.65); LASSO model performance by AUC was 0.60 (0.54-0.66) with mean dose to combined CC being the most frequent variable in both. The top three most important variables in Random Forest by mean decrease in Gini coefficient were max dose to posterior and combined CC and mean dose to anterior CC. Model performance by AUC was 0.70 (0.64-0.75). Here we present the first, to our knowledge, NTCP model for decline in attention/processing speed, along with dosimetric predictors of executive function decline. We found that after partial brain RT, dose to several ROIs significantly correlated with post-RT impairment. These data can guide future cognitive-sparing strategies for brain RT.