Slow wave sleep is associated with forgetting in patients with temporal lobe epilepsy.

While time spent in slow wave sleep (SWS) after learning promotes memory consolidation in the healthy brain, it is unclear if the same benefit is obtained in patients with temporal lobe epilepsy (TLE). Interictal epileptiform discharges (IEDs) are potentiated during SWS and thus may disrupt memory consolidation processes thought to depend on hippocampal-neocortical interactions. Here, we explored the relationship between SWS, IEDs, and overnight forgetting in patients with TLE. Nineteen patients with TLE studied object-scene pairs and memory was tested across a day of wakefulness (6 hrs) and across a night of sleep (16 hrs) while undergoing continuous scalp EEG monitoring. We found that time spent in SWS after learning was related to greater forgetting overnight. Longer duration in SWS and number of IEDs were each associated with greater forgetting, although the number of IEDs did not mediate the relationship between SWS and memory. Further research, particularly with intracranial recordings, is required to identify the mechanisms by which SWS and IEDs can be pathological to sleep-dependent memory consolidation in patients with TLE.

Mechanical pain sensitivity is associated with hippocampal structural integrity.

ABSTRACT: Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage-ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity-the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.

Cognitive Outcomes After Antidepressant Pharmacotherapy for Late-Life Depression: A Systematic Review and Meta-Analysis.

OBJECTIVE: The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function. METHODS: A systematic review and meta-analysis of prospective studies of antidepressant pharmacotherapy for adults age 50 or older (or mean age of 65 or older) with LLD was conducted. MEDLINE, EMBASE, and PsycInfo were searched through December 31, 2022. The primary outcome was a change on cognitive test scores from baseline to after treatment. Secondary outcomes included the effects of specific medications and the associations between changes in depressive symptoms and cognitive test scores. Participants with bipolar disorder, psychotic depression, dementia, or neurological disease were excluded. Findings from all eligible studies were synthesized at a descriptive level, and a random-effects model was used to pool the results for meta-analysis. RESULTS: Twenty-two studies were included. Thirteen of 19 studies showed an improvement on at least one cognitive test after antidepressant pharmacotherapy, with the most robust evidence for the memory and learning (nine of 16 studies) and processing speed (seven of 10 studies) domains and for sertraline (all five studies). Improvements in depressive symptoms were associated with improvement in cognitive test scores in six of seven relevant studies. The meta-analysis (eight studies; N=493) revealed a statistically significant overall improvement in memory and learning (five studies: effect size=0.254, 95% CI=0.103-0.404, SE=0.077); no statistically significant changes were seen in other cognitive domains. The evaluated risk of publication bias was low. CONCLUSION: Antidepressant pharmacotherapy of LLD appears to improve certain domains of cognitive function, particularly memory and learning. This effect may be mediated by an improvement in depressive symptoms. Studies comparing individuals receiving pharmacotherapy with untreated control participants are needed.

Emergence Patterns from General Anesthesia after Epilepsy Surgery: An Observational Pilot Study.

Objective Emergence from anesthesia starts from the limbic structures and then spreads outwards to brainstem, reticular activating systems, and then to the cortex. Epilepsy surgery often involves resection of limbic structures and hence may disrupt the pattern of emergence. The aim of this study was to explore the pattern of emergence from anesthesia following epilepsy surgery and to determine associated variables affecting the emergence pattern. Setting and Design Tertiary care center, prospective observational study. Materials and Methods We conducted a prospective observation pilot study on adult patients undergoing anterior temporal lobectomy and amygdalohippocampectomy for epilepsy. Anesthesia management was standardized in all patients, and they were allowed to wake up with "no touch" technique. Primary outcome of the study was the pattern of emergence (normal emergence, agitated emergence, or slow emergence) from anesthesia. Secondary outcomes were to explore the differences in preoperative neuropsychological profile and limbic structure volumes between the different patterns of emergence. Quantitative variables were analyzed using Student's t -test. Qualitative variables were analyzed using chi-square test. Results Twenty-nine patients completed the study: 9 patients (31%) had agitated emergence, and 20 patients had normal emergence. Among the agitated emergence, 2 patients had Riker scale of 7 indicating violent emergence. Patient demographics, anesthetic used, neuropsychological profile, and limbic structure volumes were similar between normal emergence and agitated emergence groups. However, two patients who had severe agitation (Riker scale of 7) had the lowest intelligence quotient. Conclusion Our pilot study showed that emergence agitation is not uncommon in patients undergoing epilepsy surgery. However, due to smaller sample size, the role of preoperative neuropsychologic profile and hippocampal volumes in predicting the pattern of emergence is inconclusive.

Leveraging the resting brain to predict memory decline after temporal lobectomy.

OBJECTIVE: Predicting memory morbidity after temporal lobectomy in patients with temporal lobe epilepsy (TLE) relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly considered a network disorder, and memory a network phenomenon. We assessed the utility of functional network measures to predict postoperative memory changes. METHODS: Seventy-two adults with TLE (37 left/35 right) underwent preoperative resting-state functional magnetic resonance imaging and pre- and postoperative neuropsychological assessment. We compared functional connectivity throughout the memory network of each patient to a healthy control template (n = 19) to identify differences in global organization. A second metric indicated the degree of integration of the to-be-resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical variables as predictors of memory change after surgery. RESULTS: Left TLE patients with more atypical memory networks, and with greater functional integration of the to-be-resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change, outperforming standard clinical and demographic variables. None of the variables examined was associated with visuospatial memory change in patients with right TLE. SIGNIFICANCE: Resting-state connectivity provides valuable information concerning both the integrity of to-be-resected tissue and functional reserve across memory-relevant regions outside of the to-be-resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision-making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE.

Exploring the merits of research performance measures that comply with the San Francisco Declaration on Research Assessment and strategies to overcome barriers of adoption: qualitative interviews with administrators and researchers.

BACKGROUND: In prior research, we identified and prioritized ten measures to assess research performance that comply with the San Francisco Declaration on Research Assessment, a principle adopted worldwide that discourages metrics-based assessment. Given the shift away from assessment based on Journal Impact Factor, we explored potential barriers to implementing and adopting the prioritized measures. METHODS: We identified administrators and researchers across six research institutes, conducted telephone interviews with consenting participants, and used qualitative description and inductive content analysis to derive themes. RESULTS: We interviewed 18 participants: 6 administrators (research institute business managers and directors) and 12 researchers (7 on appointment committees) who varied by career stage (2 early, 5 mid, 5 late). Participants appreciated that the measures were similar to those currently in use, comprehensive, relevant across disciplines, and generated using a rigorous process. They also said the reporting template was easy to understand and use. In contrast, a few administrators thought the measures were not relevant across disciplines. A few participants said it would be time-consuming and difficult to prepare narratives when reporting the measures, and several thought that it would be difficult to objectively evaluate researchers from a different discipline without considerable effort to read their work. Strategies viewed as necessary to overcome barriers and support implementation of the measures included high-level endorsement of the measures, an official launch accompanied by a multi-pronged communication strategy, training for both researchers and evaluators, administrative support or automated reporting for researchers, guidance for evaluators, and sharing of approaches across research institutes. CONCLUSIONS: While participants identified many strengths of the measures, they also identified a few limitations and offered corresponding strategies to address the barriers that we will apply at our organization. Ongoing work is needed to develop a framework to help evaluators translate the measures into an overall assessment. Given little prior research that identified research assessment measures and strategies to support adoption of those measures, this research may be of interest to other organizations that assess the quality and impact of research.

DORA-compliant measures of research quality and impact to assess the performance of researchers in biomedical institutions: Review of published research, international best practice and Delphi survey.

OBJECTIVE: The San Francisco Declaration on Research Assessment (DORA) advocates for assessing biomedical research quality and impact, yet academic organizations continue to employ traditional measures such as Journal Impact Factor. We aimed to identify and prioritize measures for assessing research quality and impact. METHODS: We conducted a review of published and grey literature to identify measures of research quality and impact, which we included in an online survey. We assembled a panel of researchers and research leaders, and conducted a two-round Delphi survey to prioritize measures rated as high (rated 6 or 7 by ≥ 80% of respondents) or moderate (rated 6 or 7 by ≥ 50% of respondents) importance. RESULTS: We identified 50 measures organized in 8 domains: relevance of the research program, challenges to research program, or productivity, team/open science, funding, innovations, publications, other dissemination, and impact. Rating of measures by 44 panelists (60%) in Round One and 24 (55%) in Round Two of a Delphi survey resulted in consensus on the high importance of 5 measures: research advances existing knowledge, research plan is innovative, an independent body of research (or fundamental role) supported by peer-reviewed research funding, research outputs relevant to discipline, and quality of the content of publications. Five measures achieved consensus on moderate importance: challenges to research productivity, potential to improve health or healthcare, team science, collaboration, and recognition by professional societies or academic bodies. There was high congruence between researchers and research leaders across disciplines. CONCLUSIONS: Our work contributes to the field by identifying 10 DORA-compliant measures of research quality and impact, a more comprehensive and explicit set of measures than prior efforts. Research is needed to identify strategies to overcome barriers of use of DORA-compliant measures, and to "de-implement" traditional measures that do not uphold DORA principles yet are still in use.

Subcortical language localization using sign language and awake craniotomy for dominant posterior temporal glioma resection in a hearing-impaired patient.

Intraoperative direct cortical stimulation (DCS) is the gold standard technique to maximize the extent of resection of tumors located in eloquent areas. To date, there are three cases reported of awake mapping for language centers in deaf patients who could communicate only with sign language. We present the case of DCS in a deaf patient who could communicate vocally, native to American Sign Language and English, that underwent intraoperative awake mapping. DCS showed similar disruption of expressive phonology to both pictorial and gestural stimuli, confirming that sign language follows the same pattern as oral language.

Age-related effects on the anterior and posterior hippocampal volumes in 6-21 year olds: A model selection approach.

Although recent studies support significant differences in intrinsic structure, function, and connectivity along the longitudinal axis of the hippocampus, few studies have investigated the normative development of this dimension. In addition, factors known to influence hippocampal structure, such as sex or puberty, have yet to be characterized when assessing age-related effects on its subregions. This study addresses this gap by investigating the relationship of the anterior (antHC) and posterior (postHC) hippocampus volumes with age, and how these are moderated by sex or puberty, in structural magnetic resonance imaging scans from 183 typically developing participants aged 6-21 years. Based on previous literature, we first anticipated that non-linear models would best represent the relationship between age and the antHC and postHC volumes. We found that age-related effects are region-specific, such that the antHC volume remains stable with increasing age, while the postHC shows a cubic function characterized by overall volume increase with age but a slower rate during adolescence. Second, we hypothesized that models, which include biological sex or pubertal status would best describe these relationships. Contrary to expectation, models comprising either biological sex or pubertal status did not significantly improve model performance. Further longitudinal research is needed to evaluate their effects on the antHC and postHC development.

Schemas provide a scaffold for neocortical integration of new memories over time.

Memory transformation is increasingly acknowledged in theoretical accounts of systems consolidation, yet how memory quality and neural representation change over time and how schemas influence this process remains unclear. We examined the behavioral quality and neural representation of schema-congruent and incongruent object-scene pairs retrieved across 10-minutes and 72-hours using fMRI. When a congruent schema was available, memory became coarser over time, aided by post-encoding coupling between the anterior hippocampus and medial prefrontal cortex (mPFC). Only schema-congruent representations were integrated in the mPFC over time, and were organized according to schematic context. In the hippocampus, pattern similarity changed across 72-hours such that the posterior hippocampus represented specific details and the anterior hippocampus represented the general context of specific memories, irrespective of congruency. Our findings suggest schemas are used as a scaffold to facilitate neocortical integration of congruent information, and illustrate evolution in hippocampal organization of detailed contextual memory over time.

Imaging in medically refractory epilepsy at 3 Tesla: a 13-year tertiary adult epilepsy center experience.

OBJECTIVES: MRI negative epilepsy has evolved through increased usage of 3 T and insights from surgically correlated studies. The goal of this study is to describe dedicated 3 T epilepsy MRI findings in medically refractory epilepsy (MRE) patients at a tertiary epilepsy center to familiarize radiologists with an updated spectrum and frequency of potential imaging findings in the adult MRE population. METHODS: Included were all patients with MRE admitted to the epilepsy monitoring unit who were discussed at weekly interdisciplinary imaging conferences at Toronto Western Hospital with MRI studies (3 T with dedicated epilepsy protocol) performed between January 2008 and January 2021. Lesion characterization was performed by two readers based on most likely imaging diagnosis in consensus. Lobes involved per case were recorded. RESULTS: A total of 738 patients (386 female; mean age 35 years, range 15-77) were included. A total of 262 patients (35.5%) were MRI negative. The most common imaging finding was mesial temporal sclerosis, seen in 132 patients (17.9%), followed by encephalomalacia and gliosis, either posttraumatic, postoperative, postischemic, or postinfectious in nature, in 79 patients (10.7%). The most common lobar involvement (either partially or uniquely) was temporal (341 cases, 58.6%). MRE patients not candidates for surgical resection were included in the study, as were newly described pathologies from surgically correlated studies revealing findings seen retrospectively on reported MRI negative exams (isolated enlargement of the amygdala, temporal pole white matter abnormality, temporal encephalocele). CONCLUSION: This study provides an updated description of the spectrum of 3 T MRI findings in adult MRE patients from a tertiary epilepsy center.

I remember therefore I am: Episodic memory retrieval and self-reported trait empathy judgments in young and older adults and individuals with medial temporal lobe excisions.

How do we know what sort of people we are? Do we reflect on specific past instances of our own behaviour, or do we just have a general idea? Previous work has emphasized the role of personal semantic memory (general autobiographical knowledge) in how we assess our own personality traits. Using a standardized trait empathy questionnaire, we show in four experiments that episodic autobiographical memory (memory for specific personal events) is associated with people's judgments of their own trait empathy. Specifically, neurologically healthy young adults rated themselves as more empathic on questionnaire items that cued episodic memories of events in which they behaved empathically. This effect, however, was diminished in people who are known to have poor episodic memory: older adults and individuals who have undergone unilateral excision of medial temporal lobe tissue (as treatment for epilepsy). Further, self-report ratings on individual questionnaire items were generally predicted by subjectively rated phenomenological qualities of the memories cued by those items, such as sensory detail, scene coherence, and overall vividness. We argue that episodic and semantic memory play different roles with respect to self-knowledge depending on life experience, the integrity of the medial temporal lobes, and whether one is assessing general abstract traits versus more concrete behaviours that embody these traits. Future research should examine different types of self-knowledge as well as personality traits other than empathy.

Baseline resting-state functional connectivity determines subsequent pain ratings to a tonic ecologically valid experimental model of orofacial pain.

ABSTRACT: Pain is a subjective experience with significant individual differences. Laboratory studies investigating pain thresholds and experimental acute pain have identified structural and functional neural correlates. However, these types of pain stimuli have limited ecological validity to real-life pain experiences. Here, we use an orthodontic procedure-the insertion of an elastomeric separator between teeth-which typically induces mild to moderate pain that peaks within 2 days and lasts several days. We aimed to determine whether the baseline structure and resting-state functional connectivity of key regions along the trigeminal nociceptive and pain modulatory pathways correlate with subsequent peak pain ratings. Twenty-six healthy individuals underwent structural and resting-state functional MRI scanning before the placement of a separator between the first molar and second premolar, which was kept in place for 5 days. Participants recorded pain ratings 3 times daily on a 100-mm visual analogue scale. Peak pain was not significantly correlated with diffusion metrics of the trigeminal nerve or gray matter volume of any brain region. Peak pain did, however, positively correlate with baseline resting-state functional connectivity between the thalamus contralateral to the separator and bilateral insula, and negatively correlated with connectivity between the periaqueductal gray (PAG) and core nodes of the default mode network (medial prefrontal and posterior cingulate cortices). The ascending (thalamic) nociceptive and the descending (PAG) pain modulatory pathways at baseline each explained unique variation in peak pain intensity ratings. In sum, preinterventional functional neural architecture of both systems determined the individual pain experience to a subsequent ecologically valid pain stimulus.

Impact of Mesial Temporal Lobe Resection on Brain Structure in Medically Refractory Epilepsy.

OBJECTIVE: Surgical resection can decrease seizure frequency in medically intractable temporal lobe epilepsy. However, the functional and structural consequences of this intervention on brain circuitry are poorly understood. We investigated structural changes that occur in brain circuits after mesial temporal lobe resection for refractory epilepsy. Specifically, we used neuroimaging techniques to evaluate changes in 1) contralesional hippocampal and bilateral mammillary body volume and 2) brain-wide cortical thickness. METHODS: Serial T1-weighted brain magnetic resonance images were acquired before and after surgery (1.6 ± 0.5 year interval) in 21 patients with temporal lobe epilepsy (9 women, 12 men; mean age, 39.4 ± 11.5 years) who had undergone unilateral temporal lobe resection (14 anterior temporal lobectomy; 7 selective amygdalohippocampectomy). Blinded manual segmentation of the unresected hippocampal formation and bilateral mammillary bodies was performed using the Pruessner and Copenhaver protocols, respectively. Brain-wide cortical thickness estimates were computed using the CIVET pipeline. RESULTS: Surgical resection was associated with a 5% reduction in contralesional hippocampal volume (P < 0.01) and a 9.5% reduction in mammillary body volume (P = 0.03). In addition, significant changes in cortical thickness were observed in contralesional anterior and middle cingulate gyrus and insula (Pfalse discovery rate < 0.01) as well as in other temporal, frontal, and occipital regions (Pfalse discovery rate < 0.05). Postoperative verbal memory function was significantly associated with cortical thickness change in contralesional inferior temporal gyrus (R2 = 0.39; P = 0.03). CONCLUSIONS: These results indicate that mesial temporal lobe resection is associated with both volume loss in spared Papez circuitry and changes in cortical thickness across the brain.

Nomograms to Predict Verbal Memory Decline After Temporal Lobe Resection in Adults With Epilepsy.

OBJECTIVE: To develop and externally validate models to predict the probability of postoperative verbal memory decline in adults following temporal lobe resection (TLR) for epilepsy using easily-accessible preoperative clinical predictors. METHODS: Multivariable models were developed to predict delayed verbal memory outcome on three commonly used measures: Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from Wechsler Memory Scale-Third Edition. Using Harrell's step-down procedure for variable selection, models were developed in 359 adults who underwent TLR at Cleveland Clinic and validated in 290 adults at one of five epilepsy surgery centers in the United States or Canada. RESULTS: Twenty-nine percent of the development cohort and 26% of the validation cohort demonstrated significant decline on at least one verbal memory measure. Initial models had good to excellent predictive accuracy (calibration (c) statistic range=0.77-0.80) in identifying patients with memory decline; however, models slightly underestimated decline in the validation cohort. Model coefficients were updated using data from both cohorts to improve stability. The model for RAVLT included surgery side, baseline memory score, and hippocampal resection. The models for LM and VPA included surgery side, baseline score, and education. Updated model performance was good to excellent (RAVLT c=0.81, LM c=0.76, VPA c=0.78). Model calibration was very good, indicating no systematic over- or under-estimation of risk. CONCLUSIONS: Nomograms are provided in two easy-to-use formats to assist clinicians in estimating the probability of verbal memory decline in adults considering TLR for treatment of epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that multivariable prediction models accurately predict verbal memory decline after temporal lobe resection for epilepsy in adults.

The psychological burden of waiting for procedures and patient-centred strategies that could support the mental health of wait-listed patients and caregivers during the COVID-19 pandemic: A scoping review.

BACKGROUND: Waiting for procedures delayed by COVID-19 may cause anxiety and related adverse consequences. OBJECTIVE: To synthesize research on the mental health impact of waiting and patient-centred mitigation strategies that could be applied in the COVID-19 context. METHODS: Using a scoping review approach, we searched 9 databases for studies on waiting lists and mental health and reported study characteristics, impacts and intervention attributes and outcomes. RESULTS: We included 51 studies that focussed on organ transplant (60.8%), surgery (21.6%) or cancer management (13.7%). Most patients and caregivers reported anxiety, depression and poor quality of life, which deteriorated with increasing wait time. The impact of waiting on mental health was greater among women and new immigrants, and those of younger age, lower socio-economic status, or with less-positive coping ability. Six studies evaluated educational strategies to develop coping skills: 2 reduced depression (2 did not), 1 reduced anxiety (2 did not) and 2 improved quality of life (2 did not). In contrast, patients desired acknowledgement of concerns, peer support, and periodic communication about wait-list position, prioritization criteria and anticipated procedure date. CONCLUSIONS: Findings revealed patient-centred strategies to alleviate the mental health impact of waiting for procedures. Ongoing research should explore how to optimize the impact of those strategies for diverse patients and caregivers, particularly in the COVID-19 context. PATIENT OR PUBLIC CONTRIBUTION: Six patients and four caregivers waiting for COVID-19-delayed procedures helped to establish eligibility criteria, plan data extraction and review a draft and final report.

Lateralizing magnetic resonance imaging findings in mesial temporal sclerosis and correlation with seizure and neurocognitive outcome after temporal lobectomy.

BACKGROUND: Mesial temporal sclerosis (MTS) is the most common cause of temporal lobe epilepsy (TLE). While MTS is associated with a high cure rate after temporal lobectomy (TL), postoperative neurocognitive deficits are common, and a subset of patients may continue to have refractory seizures. OBJECTIVE: To use magnetic resonance (MR) volumetry to identify features of the mesial temporal lobe in patients with MTS that correlate with seizure and neurocognitive outcome after temporal lobectomy. METHODS: Thirty-five patients with unilateral MTS, high-resolution MR imaging, and at least one year of postoperative assessments were retrospectively examined. Volumetric analysis of the hippocampus, parahippocampal gyrus (PHG) and FLAIR hyperintensity of the affected temporal lobe was performed. TL resections were manually segmented, and resection heat maps reflecting seizure outcome were produced. The degree of preoperative atrophy of the affected mesial structures relative to the unaffected side were related to preoperative and postoperative component scores of verbal and visuospatial memory as well as confrontation naming. RESULTS: Greater FLAIR hyperintense volume was associated with favorable seizure outcome at one year and last follow-up. Resections extending most medial and posteriorly were associated with favorable seizure outcome. In patients with left MTS, less atrophy of the affected PHG was predictive of higher preoperative naming scores and greater postoperative naming deficit, while less hippocampal atrophy was predictive of higher preoperative verbal memory component scores. CONCLUSION: Greater hippocampal FLAIR volume is associated with favorable surgical outcome. Hippocampal volume correlates with preoperative verbal memory, while PHG volume is implicated in confrontation naming ability.

An exploratory study into the influence of laterality and location of hippocampal sclerosis on seizure prognosis and global cortical thinning.

In mesial temporal lobe epilepsy (mTLE), the correlation between disease duration, seizure laterality, and rostro-caudal location of hippocampal sclerosis has not been examined in the context of seizure severity and global cortical thinning. In this retrospective study, we analyzed structural 3 T MRI from 35 mTLE subjects. Regions of FLAIR hyperintensity (as an indicator of sclerosis)-based on 2D coronal FLAIR sequences-in the hippocampus were manually segmented, independently and in duplicate; degree of segmentation agreement was confirmed using the DICE index. Segmented lesions were used for separate analyses. First, the correlation of cortical thickness with disease duration and seizure focus laterality was explored using linear model regression. Then, the relationship between the rostro-caudal location of the FLAIR hyperintense signal and seizure severity, based on the Cleveland Clinic seizure freedom score (ccSFS), was explored using probabilistic voxel-wise mapping and functional connectivity analysis from normative data. The mean DICE Index was 0.71 (range 0.60-0.81). A significant correlation between duration of epilepsy and decreased mean whole brain cortical thickness was identified, regardless of seizure laterality (p < 0.05). The slope of cortical volume loss over time, however, was greater in subjects with right seizure focus. Based on probabilistic voxel-wise mapping, FLAIR hyperintensity in the posterior hippocampus was significantly associated with lower ccSFS scores (greater seizure severity). Finally, the right hippocampus was found to have greater brain-wide connectivity, compared to the left side, based on normative connectomic data. We have demonstrated a significant correlation between duration of epilepsy and right-sided seizure focus with global cortical thinning, potentially due to greater brain-wide connectivity. Sclerosis along the posterior hippocampus was associated with greater seizure severity, potentially serving as an important biomarker of seizure outcome after surgery.