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.

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.

Event-based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data.

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10-16 ), age at onset (ρ = -.18, p = 9.82 × 10-7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features.

Impaired Behavioral Pattern Separation in Refractory Temporal Lobe Epilepsy and Mild Cognitive Impairment.

OBJECTIVE: Episodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI. METHOD: Patients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST). Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test-Second Edition scores, and MST performance were tested in the TLE group. RESULTS: Patients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance. CONCLUSION: Memory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.

Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment.

Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer's disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer's disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.

An Intracranial Electrophysiology Study of Visual Language Encoding: The Contribution of the Precentral Gyrus to Silent Reading.

Models of reading emphasize that visual (orthographic) processing provides input to phonological as well as lexical-semantic processing. Neurobiological models of reading have mapped these processes to distributed regions across occipital-temporal, temporal-parietal, and frontal cortices. However, the role of the precentral gyrus in these models is ambiguous. Articulatory phonemic representations in the precentral gyrus are obviously involved in reading aloud, but it is unclear if the precentral gyrus is recruited during reading silently in a time window consistent with participation in phonological processing contributions. Here, we recorded intracranial electrophysiology during a speeded semantic decision task from 24 patients to map the spatio-temporal flow of information across the cortex during silent reading. Patients selected animate nouns from a stream of nonanimate words, letter strings, and false-font stimuli. We characterized the distribution and timing of evoked high-gamma power (70-170 Hz) as well as phase-locking between electrodes. The precentral gyrus showed a proportion of electrodes responsive to linguistic stimuli (27%) that was at least as high as those of surrounding peri-sylvian regions. These precentral gyrus electrodes had significantly greater high-gamma power for words compared to both false-font and letter-string stimuli. In a patient with word-selective effects in the fusiform, superior temporal, and precentral gyri, there was significant phase-locking between the fusiform and precentral gyri starting at ∼180 msec and between the precentral and superior temporal gyri starting at ∼220 msec. Finally, our large patient cohort allowed exploratory analyses of the spatio-temporal reading network underlying silent reading. The distribution, timing, and connectivity results place the precentral gyrus as an important hub in the silent reading network.

Temporal Lobe Epilepsy Surgical Outcomes Can Be Inferred Based on Structural Connectome Hubs: A Machine Learning Study.

OBJECTIVE: Medial temporal lobe epilepsy (TLE) is the most common form of medication-resistant focal epilepsy in adults. Despite removal of medial temporal structures, more than one-third of patients continue to have disabling seizures postoperatively. Seizure refractoriness implies that extramedial regions are capable of influencing the brain network and generating seizures. We tested whether abnormalities of structural network integration could be associated with surgical outcomes. METHODS: Presurgical magnetic resonance images from 121 patients with drug-resistant TLE across 3 independent epilepsy centers were used to train feed-forward neural network models based on tissue volume or graph-theory measures from whole-brain diffusion tensor imaging structural connectomes. An independent dataset of 47 patients with TLE from 3 other epilepsy centers was used to assess the predictive values of each model and regional anatomical contributions toward surgical treatment results. RESULTS: The receiver operating characteristic area under the curve based on regional betweenness centrality was 0.88, significantly higher than a random model or models based on gray matter volumes, degree, strength, and clustering coefficient. Nodes most strongly contributing to the predictive models involved the bilateral parahippocampal gyri, as well as the superior temporal gyri. INTERPRETATION: Network integration in the medial and lateral temporal regions was related to surgical outcomes. Patients with abnormally integrated structural network nodes were less likely to achieve seizure freedom. These findings are in line with previous observations related to network abnormalities in TLE and expand on the notion of underlying aberrant plasticity. Our findings provide additional information on the mechanisms of surgical refractoriness. ANN NEUROL 2020;88:970-983.

Diagnosing cognitive disorders in older adults with epilepsy.

OBJECTIVE: To characterize the nature and prevalence of cognitive disorders in older adults with temporal lobe epilepsy (TLE) and compare their cognitive profiles to patients with amnestic mild cognitive impairment (ie, aMCI). METHODS: Seventy-one older patients with TLE, 77 aMCI, and 69 normal aging controls (NACs), all 55-80 years of age, completed neuropsychological measures of memory, language, executive function, and processing speed. An actuarial neuropsychological method designed to diagnose MCI was applied to individual patients to identify older adults with TLE who met diagnostic criteria for MCI (TLE-MCI). A linear classifier was performed to evaluate how well the diagnostic criteria differentiated patients with TLE-MCI from aMCI. In TLE, the contribution of epilepsy-related and vascular risk factors to cognitive impairment was evaluated using multiple regression. RESULTS: Forty-three TLE patients (60%) met criteria for TLE-MCI, demonstrating marked deficits in both memory and language. When patients were analyzed according to age at seizure onset, 63% of those with an early onset (<50 years) versus 56% of those with late onset (≥ 50 years) met criteria for TLE-MCI. A classification model between TLE-MCI and aMCI correctly classified 81.1% (90.6% specificity, 61.3% sensitivity) of the cohort based on neuropsychological scores. Whereas TLE-MCI showed greater deficits in language relative to aMCI, patients with aMCI showed greater rapid forgetting on memory measures. Both epilepsy-related risk factors and the presence of leukoaraiosis on MRI contributed to impairment profiles in TLE-MCI. SIGNIFICANCE: Cognitive impairment is a common comorbidity in epilepsy and it presents in a substantial number of older adults with TLE. Although the underlying etiologies are unknown in many patients, the TLE-MCI phenotype may be secondary to an accumulation of epilepsy and vascular risk factors, signal the onset of a neurodegenerative disease, or represent a combination of factors.

Topological alterations in older adults with temporal lobe epilepsy are distinct from amnestic mild cognitive impairment.

Epilepsy incidence and prevalence peaks in older adults, yet systematic studies of brain aging and epilepsy remain limited. We investigated topological network disruption in older adults with temporal lobe epilepsy (TLE; age > 55 years). Additionally, we examined the potential network disruption overlap between TLE and amnestic mild cognitive impairment (aMCI), the prodromal stage of Alzheimer disease. Measures of network integration ("global path efficiency") and segregation ("transitivity" and "modularity") were calculated from cortical thickness covariance from 73 TLE subjects, 79 aMCI subjects, and 70 healthy controls. Compared to controls, TLE patients demonstrated abnormal measures of segregation (increased transitivity and decreased modularity) and integration (decreased global path efficiency). aMCI patients also displayed increased transitivity and decreased global path efficiency, but these differences were less pronounced than in TLE. At the local level, TLE patients demonstrated decreased local path efficiency focused in the bilateral temporal lobes, whereas aMCI patients had a more frontal-parietal distribution. These results suggest that network disruption at the global and local level is present in both disorders, but global disruption may be a particularly salient feature in older adults with TLE. These findings motivate further research into whether these network changes have distinct cognitive correlates or are progressive in older adults with epilepsy.

Cognitive phenotypes in temporal lobe epilepsy utilizing data- and clinically driven approaches: Moving toward a new taxonomy.

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.

Correlation Structure in Micro-ECoG Recordings is Described by Spatially Coherent Components.

Electrocorticography (ECoG) is becoming more prevalent due to improvements in fabrication and recording technology as well as its ease of implantation compared to intracortical electrophysiology, larger cortical coverage, and potential advantages for use in long term chronic implantation. Given the flexibility in the design of ECoG grids, which is only increasing, it remains an open question what geometry of the electrodes is optimal for an application. Conductive polymer, PEDOT:PSS, coated microelectrodes have an advantage that they can be made very small without losing low impedance. This makes them suitable for evaluating the required granularity of ECoG recording in humans and experimental animals. We used two-dimensional (2D) micro-ECoG grids to record intra-operatively in humans and during acute implantations in mouse with separation distance between neighboring electrodes (i.e., pitch) of 0.4 mm and 0.2/0.25 mm respectively. To assess the spatial properties of the signals, we used the average correlation between electrodes as a function of the pitch. In agreement with prior studies, we find a strong frequency dependence in the spatial scale of correlation. By applying independent component analysis (ICA), we find that the spatial pattern of correlation is largely due to contributions from multiple spatially extended, time-locked sources present at any given time. Our analysis indicates the presence of spatially structured activity down to the sub-millimeter spatial scale in ECoG despite the effects of volume conduction, justifying the use of dense micro-ECoG grids.

The impact of cerebrovascular risk factors on postoperative memory decline in patients with left temporal lobe epilepsy.

Cerebrovascular risk factors (CVRFs) and comorbid cardiovascular and metabolic disease have been linked to accelerated cognitive aging and dementia in the general population; however, the contribution of these comorbidities to the risk of post anterior temporal lobectomy (ATL) memory decline has been unexamined. We explored the effects of CVRFs on postoperative verbal memory decline in a cohort of 22 patients with left temporal lobe epilepsy (LTLE) who completed pre- and one-year postsurgical neuropsychological testing. Diagnoses of interest included preoperative cardiovascular and metabolic disorders, as well as CVRFs [pulse pressure proxy, body mass index (BMI), and fasting glucose]. Twenty-three percent of patients had a history of cardiovascular disease, 9% of metabolic disorders, and 38% had a BMI indicating overweight or obese status. Higher preoperative BMI and glucose were associated with greater decline in verbal memory. The association between BMI and memory decline remained significant after controlling for age and left hippocampal volume. These findings suggest that modifiable health-related risk factors, including CVRFs, may impact the risk of postoperative cognitive decline, and that BMI in particular could be an important factor to consider and/or target for intervention early in clinical care to protect cognitive health.

Identifying the neural basis of a language-impaired phenotype of temporal lobe epilepsy.

OBJECTIVE: To identify neuroimaging and clinical biomarkers associated with a language-impaired phenotype in refractory temporal lobe epilepsy (TLE). METHODS: Eighty-five patients with TLE were characterized as language-impaired (TLE-LI) or non-language-impaired (TLE-NLI) based on comprehensive neuropsychological testing. Structural magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) were obtained in patients and 47 healthy controls (HC). fMRI activations and cortical thickness were calculated within language regions of interest, and fractional anisotropy (FA) was calculated within deep white matter tracts associated with language. Analyses of variance were performed to test for differences among the groups in imaging measures. Receiver operator characteristic curves were used to determine how well different clinical versus imaging measures discriminated TLE-LI from TLE-NLI. RESULTS: TLE-LI patients showed significantly less activation within left superior temporal cortex compared to HC and TLE-NLI, regardless of side of seizure onset. TLE-LI also showed decreased FA in the inferior longitudinal fasciculus and arcuate fasciculus compared to HC. Cortical thickness did not differ between groups in any region. A model that included language-related fMRI activations within the superior temporal gyrus, age at onset, and demographic variables was the most predictive of language impairment (area under the curve = 0.80). SIGNIFICANCE: These findings demonstrate a unique imaging signature associated with a language-impaired phenotype in TLE, characterized by functional and microstructural alterations within the language network. Reduced left superior temporal activation combined with compromise to language association tracts underlies this phenotype, extending our previous work on cognitive phenotypes that could have implications for treatment-planning or cognitive progression in TLE.

Sub-millimeter ECoG pitch in human enables higher fidelity cognitive neural state estimation.

Electrocorticography (ECoG), electrophysiological recording from the pial surface of the brain, is a critical measurement technique for clinical neurophysiology, basic neurophysiology studies, and demonstrates great promise for the development of neural prosthetic devices for assistive applications and the treatment of neurological disorders. Recent advances in device engineering are poised to enable orders of magnitude increase in the resolution of ECoG without comprised measurement quality. This enhancement in cortical sensing enables the observation of neural dynamics from the cortical surface at the micrometer scale. While these technical capabilities may be enabling, the extent to which finer spatial scale recording enhances functionally relevant neural state inference is unclear. We examine this question by employing a high-density and low impedance 400 µm pitch microECoG (µECoG) grid to record neural activity from the human cortical surface during cognitive tasks. By applying machine learning techniques to classify task conditions from the envelope of high-frequency band (70-170Hz) neural activity collected from two study participants, we demonstrate that higher density grids can lead to more accurate binary task condition classification. When controlling for grid area and selecting task informative sub-regions of the complete grid, we observed a consistent increase in mean classification accuracy with higher grid density; in particular, 400 µm pitch grids outperforming spatially sub-sampled lower density grids up to 23%. We also introduce a modeling framework to provide intuition for how spatial properties of measurements affect the performance gap between high and low density grids. To our knowledge, this work is the first quantitative demonstration of human sub-millimeter pitch cortical surface recording yielding higher-fidelity state estimation relative to devices at the millimeter-scale, motivating the development and testing of µECoG for basic and clinical neurophysiology as well as towards the realization of high-performance neural prostheses.

Neurocognitive stages of spatial cognitive mapping measured during free exploration of a large-scale virtual environment.

Using a novel, fully mobile virtual reality paradigm, we investigated the EEG correlates of spatial representations formed during unsupervised exploration. On day 1, subjects implicitly learned the location of 39 objects by exploring a room and popping bubbles that hid the objects. On day 2, they again popped bubbles in the same environment. In most cases, the objects hidden underneath the bubbles were in the same place as on day 1. However, a varying third of them were misplaced in each block. Subjects indicated their certainty that the object was in the same location as the day before. Compared with bubble pops revealing correctly placed objects, bubble pops revealing misplaced objects evoked a decreased negativity starting at 145 ms, with scalp topography consistent with generation in medial parietal cortex. There was also an increased negativity starting at 515 ms to misplaced objects, with scalp topography consistent with generation in inferior temporal cortex. Additionally, misplaced objects elicited an increase in frontal midline theta power. These findings suggest that the successive neurocognitive stages of processing allocentric space may include an initial template matching, integration of the object within its spatial cognitive map, and memory recall, analogous to the processing negativity N400 and theta that support verbal cognitive maps in humans.

Modular Phoneme Processing in Human Superior Temporal Gyrus.

Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200µm pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

Pharmacologically increasing sleep spindles enhances recognition for negative and high-arousal memories.

Sleep affects declarative memory for emotional stimuli differently than it affects declarative memory for nonemotional stimuli. However, the interaction between specific sleep characteristics and emotional memory is not well understood. Recent studies on how sleep affects emotional memory have focused on rapid eye movement sleep (REM) but have not addressed non-REM sleep, particularly sleep spindles. This is despite the fact that sleep spindles are implicated in declarative memory as well as neural models of memory consolidation (e.g., hippocampal neural replay). Additionally, many studies examine a limited range of emotional stimuli and fail to disentangle differences in memory performance because of variance in valence and arousal. Here, we experimentally increase non-REM sleep features, sleep spindle density, and SWS, with pharmacological interventions using zolpidem (Ambien) and sodium oxybate (Xyrem) during daytime naps. We use a full spread of emotional stimuli to test all levels of valence and arousal. We find that increasing sleep spindle density increases memory discrimination (da) for highly arousing and negative stimuli without altering measures of bias (ca). These results indicate a broader role for sleep in the processing of emotional stimuli with differing effects based on arousal and valence, and they raise the possibility that sleep spindles causally facilitate emotional memory consolidation. These findings are discussed in terms of the known use of hypnotics in individuals with emotional mood disorders.

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.

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.