Computerized adaptive test strategies for the matrix reasoning subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV).

OBJECTIVE: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT). METHOD: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40). RESULTS: The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3-7 items had to be administered for a large percentage of individuals. CONCLUSIONS: This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

Comparison of minimally invasive to standard temporal lobectomy approaches to epilepsy surgery: Seizure relief and visual confrontation naming outcomes.

The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher's exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each.

Stereoelectroencephalography-guided radiofrequency ablation of the epileptogenic zone as a treatment and predictor of future success of further surgical intervention.

OBJECTIVE: Stereoelectroencephalography (SEEG)-guided radiofrequency ablation (RFA) is increasingly being used as a treatment for drug-resistant localization-related epilepsy. The aim of this study is to analyze the successes and failures using RFA and how response correlates with surgical epilepsy treatment outcomes. METHODS: We retrospectively reviewed 62 patients who underwent RFA via SEEG electrodes. After excluding five, the remaining 57 were classified into subgroups based on procedures and outcomes. Forty patients (70%) underwent a secondary surgical procedure, of whom 32 were delayed: 26 laser interstitial thermal therapy (LITT), five resection, one neuromodulation. We determined the predictive value of RFA outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the transient time of seizure freedom after RFA were calculated for each patient. RESULTS: Twelve of 49 patients (24.5%) who had RFA alone and delayed follow-up achieved Engel class I. Of the 32 patients who underwent a delayed secondary surgical procedure, 15 achieved Engel class I and nine Engel class II (24 successes), and eight were considered failures (Engel class III/IV). The transient time of seizure freedom after RFA was significantly longer in the success group (4 months, SD = 2.6) as compared to the failure group (.75 months, SD = 1.16; p < .001). Additionally, there was a higher portion of preoperative lesional findings in patients in the RFA alone and delayed surgical success group (p = .03) and a longer time to seizure recurrence in the presence of lesions (p < .05). Side effects occurred in 1% of patients. SIGNIFICANCE: In this series, RFA provided a treatment during SEEG-guided intracranial monitoring that led to seizure freedom in ~25% of patients. Of the 70% who underwent delayed surgery, longer transient time of seizure freedom after RFA was predictive of the results of the secondary surgeries, 74% of which were LITT.

An ERP measure of non-conscious memory reveals dissociable implicit processes in human recognition using an open-source automated analytic pipeline.

Non-conscious processing of human memory has traditionally been difficult to objectively measure and thus understand. A prior study on a group of hippocampal amnesia (N = 3) patients and healthy controls (N = 6) used a novel procedure for capturing neural correlates of implicit memory using event-related potentials (ERPs): old and new items were equated for varying levels of memory awareness, with ERP differences observed from 400 to 800 ms in bilateral parietal regions that were hippocampal-dependent. The current investigation sought to address the limitations of that study by increasing the sample of healthy subjects (N = 54), applying new controls for construct validity, and developing an improved, open-source tool for automated analysis of the procedure used for equating levels of memory awareness. Results faithfully reproduced prior ERP findings of parietal effects that a series of systematic control analyses validated were not contributed to nor contaminated by explicit memory. Implicit memory effects extended from 600 to 1000 ms, localized to right parietal sites. These ERP effects were found to be behaviorally relevant and specific in predicting implicit memory response times, and were topographically dissociable from other traditional ERP measures of implicit memory (miss vs. correct rejections) that instead occurred in left parietal regions. Results suggest first that equating for reported awareness of memory strength is a valid, powerful new method for revealing neural correlates of non-conscious human memory, and second, behavioral correlations suggest that these implicit effects reflect a pure form of priming, whereas misses represent fluency leading to the subjective experience of familiarity.

Intracranial investigation of piriform cortex epilepsy during odor presentation.

The piriform cortex (PC) is part of the olfactory system, principally receiving input from the lateral olfactory tract and projecting to downstream components of the olfactory network, including the amygdala. Based on preclinical studies, PC is vulnerable to injury and can be easily kindled as an onset site for seizures. While the role of PC in human epilepsy has been studied indirectly and the subject of speculation, cases of demonstrated PC seizure onset from direct intracranial recording are rare. We present a pediatric patient with drug-resistant focal reflex epilepsy and right mesial temporal sclerosis with habitual seizures triggered by coconut aroma. The patient underwent stereoelectroencephalography with implantation of olfactory cortices including PC, through which we identified PC seizure onset, mapped high-frequency activity associated with presentation of olfactory stimuli and performance on cognitive tasks, and reproduced habitual seizures via cortical stimulation of PC. Coconut odor did not trigger seizures in our work with the patient. Surgical workup resulted in resection of the patient's right amygdala, PC, and mesial temporal pole, following which she has been seizure free for 20 months without functional decline in cognition or smell. Histological findings from resected tissue showed astrogliosis and subpial gliosis.

Psychiatric changes after stereotactic laser amygdalohippocampotomy for medial temporal lobe epilepsy.

PURPOSE: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for drug-resistant temporal lobe epilepsy (TLE) that has comparable rates of seizure freedom to traditional open resective TLE surgery. The objective of this study was to determine psychiatric outcome (i.e., depression and anxiety changes, psychosis) after SLAH, to explore possible contributory factors to these changes, and to determine the prevalence of de novo psychopathology. METHODS: We explored mood and anxiety in 37 adult patients with TLE undergoing SLAH using the Beck psychiatric symptoms scales (i.e., Beck Depression Inventory-II [BDI-II] and Beck Anxiety Inventory [BAI]) preoperatively and 6 months following surgery. Multivariable regression analysis was conducted to identify predictors of worse depression or anxiety symptoms following SLAH. The prevalence of de novo psychopathology following SLAH was also determined. RESULTS: We found a significant decrease in BDI-II (mean decline from 16.3 to 10.9, p = 0.004) and BAI (mean decline from 13.3 to 9.0, p = 0.045) scores following SLAH at the group level. While the rate of resolution of depression (from 62% to 49%) did not achieve statistical significance (p = 0.13, McNemar's), the rate of resolution of anxiety (from 57% to 35%) was statistically significant (p = 0.03, McNemar's). The de novo rate of psychopathology (i.e., new onset depression or anxiety) following SLAH was 1 of 7 (14%). Using a metric of meaningful change rather than complete symptom resolution, 16 of 37 (43%) patients experienced improvement in depression and 6 of 37 (16%) experienced worsening. For anxiety, 14 of 37 (38%) experienced meaningful improvement and 8 of 37 (22%) experienced worsening. Baseline performance on the Beck Scales was the only factor contributing to outcome status. DISCUSSION: In one of the first studies to evaluate psychiatric outcomes after SLAH, we found promising overall trends toward stability or significant improvement in symptom burden at the group level for both depression and anxiety. There was also a significant improvement in clinical anxiety, though the decrease in clinical depression was not significant, likely owing to the limitations of sample size. SLAH may improve overall psychiatric symptoms, similarly to traditional resective TLE surgery, but de novo psychopathology and postoperative psychiatric morbidity remain significant issues, and larger samples are necessary to determine causal contributory factors.

The effect of responsive neurostimulation (RNS) on neuropsychiatric and psychosocial outcomes in drug-resistant epilepsy.

OBJECTIVE: The impact of responsive neurostimulation (RNS) on neuropsychiatric and psychosocial outcomes has not been extensively evaluated outside of the original clinical trials and post-approval studies. The goal of this study was to ascertain the potential real-world effects of RNS on cognitive, psychiatric, and quality of life (QOL) outcomes in relation to seizure outcomes by examining 50 patients undergoing RNS implantation for drug-resistant epilepsy (DRE). METHODS: We performed a retrospective review of all patients treated at our institution with RNS for DRE with at least 12 months of follow-up. In addition to baseline demographic and disease-related characteristics, we collected cognitive (Full-Scale Intelligence Quotient, Verbal Comprehension, and Perceptual Reasoning Index), psychiatric (Beck Depression and Anxiety Inventory Scores), and QOL (QOLIE-31) outcomes at 6 and 12 months after RNS implantation and correlated them with seizure outcomes. RESULTS: Fifty patients (median age 39.5 years, 64% female) were treated with RNS for DRE in our institution from 2005 to 2020. Of the 37 of them who had well-documented pre and post-implantation seizure diaries, the 6-month median seizure frequency reduction was 88%, the response rate (50% or greater seizure frequency reduction) was 78%, and 32% of patients were free of disabling seizures in this timeframe. There was no statistically significant difference at a group level in any of the evaluated cognitive, psychiatric, and QOL outcomes at 6 and 12 months post-implantation compared to the pre-implantation baseline, irrespective of seizure outcomes, although a subset of patients experienced a decline in mood or cognitive variables. SIGNIFICANCE: Responsive neurostimulation does not appear to have a statistically significant negative or positive impact on neuropsychiatric and psychosocial status at the group level. We observed significant variability in outcome, with a minority of patients experiencing worse behavioral outcomes, which seemed related to RNS implantation. Careful outcome monitoring is required to identify the subset of patients experiencing a poor response and to make appropriate adjustments in care.

A virtual reality paradigm with dynamic scene stimuli for use in memory research.

Episodic memory may essentially be memory for one's place within a temporally unfolding scene from a first-person perspective. Given this, pervasively used static stimuli may only capture one small part of episodic memory. A promising approach for advancing the study of episodic memory is immersing participants within varying scenes from a first-person perspective. We present a pool of distinct scene stimuli for use in virtual environments and a paradigm that is implementable across varying levels of immersion on multiple virtual reality (VR) platforms and adaptable to studying various aspects of scene and episodic memory. In our task, participants are placed within a series of virtual environments from a first-person perspective and guided through a virtual tour of scenes during a study phase and a test phase. In the test phase, some scenes share a spatial layout with studied scenes; others are completely novel. In three experiments with varying degrees of immersion, we measure scene recall, scene familiarity-detection during recall failure, the subjective experience of déjà vu, the ability to predict the next turn on a tour, the subjective sense of being able to predict the next turn on a tour, and the factors that influence memory search and the inclination to generate candidate recollective information. The level of first-person immersion mattered to multiple facets of episodic memory. The paradigm presents a useful means of advancing mechanistic understanding of how memory operates in realistic dynamic scene environments, including in combination with cognitive neuroscience methods such as functional magnetic resonance imaging and electrophysiology.

Opening a conceptual space for metamemory experience.

The experiences associated with remembering, including metamemory feelings about the act of remembering and attempts at remembering, are not often integrated into general accounts of memory. For example, David Rubin (2022) proposes a unified, three-dimensional conceptual space for mapping memory states, a map that does not systematically specify metamemory feelings. Drawing on Rubin's model, we define a distinct role for metamemory in relation to first-order memory content. We propose a fourth dimension for the model and support the proposal with conceptual, neurocognitive, and clinical lines of reasoning. We use the modified model to illustrate several cases, and show how it helps to conceptualize a new category of memory state: autonoetic knowing, exemplified by déjà vu. We also caution not to assume that memory experience is directly correlated with or caused by memory content, an assumption Tulving (1989) labeled the doctrine of concordance.

White matter association tracts underlying language and theory of mind: An investigation of 809 brains from the Human Connectome Project.

Language and theory of mind (ToM) are the cognitive capacities that allow for the successful interpretation and expression of meaning. While functional MRI investigations are able to consistently localize language and ToM to specific cortical regions, diffusion MRI investigations point to an inconsistent and sometimes overlapping set of white matter tracts associated with these two cognitive domains. To further examine the white matter tracts that may underlie these domains, we use a two-tensor tractography method to investigate the white matter microstructure of 809 participants from the Human Connectome Project. 20 association white matter tracts (10 in each hemisphere) are uniquely identified by leveraging a neuroanatomist-curated automated white matter tract atlas. The fractional anisotropy (FA), mean diffusivity (MD), and number of streamlines (NoS) are measured for each white matter tract. Performance on neuropsychological assessments of semantic memory (NIH Toolbox Picture Vocabulary Test, TPVT) and emotion perception (Penn Emotion Recognition Test, PERT) are used to measure critical subcomponents of the language and ToM networks, respectively. Regression models are constructed to examine how structural measurements of left and right white matter tracts influence performance across these two assessments. We find that semantic memory performance is influenced by the number of streamlines of the left superior longitudinal fasciculus III (SLF-III), and emotion perception performance is influenced by the number of streamlines of the right SLF-III. Additionally, we find that performance on both semantic memory & emotion perception is influenced by the FA of the left arcuate fasciculus (AF). The results point to multiple, overlapping white matter tracts that underlie the cognitive domains of language and ToM. Results are discussed in terms of hemispheric dominance and concordance with prior investigations.

Central Nervous System Manifestations of COVID-19: A Critical Review and Proposed Research Agenda.

OBJECTIVE: On March 11, 2020, the World Health Organization declared an outbreak of a new viral entity, coronavirus 2019 (COVID-19), to be a worldwide pandemic. The characteristics of this virus, as well as its short- and long-term implications, are not yet well understood. The objective of the current paper was to provide a critical review of the emerging literature on COVID-19 and its implications for neurological, neuropsychiatric, and cognitive functioning. METHOD: A critical review of recently published empirical research, case studies, and reviews pertaining to central nervous system (CNS) complications of COVID-19 was conducted by searching PubMed, PubMed Central, Google Scholar, and bioRxiv. RESULTS: After considering the available literature, areas thought to be most pertinent to clinical and research neuropsychologists, including CNS manifestations, neurologic symptoms/syndromes, neuroimaging, and potential long-term implications of COVID-19 infection, were reviewed. CONCLUSION: Once thought to be merely a respiratory virus, the scientific and medical communities have realized COVID-19 to have broader effects on renal, vascular, and neurological body systems. The question of cognitive deficits is not yet well studied, but neuropsychologists will undoubtedly play an important role in the years to come.

Rationale and Design of the National Neuropsychology Network.

OBJECTIVE: The National Neuropsychology Network (NNN) is a multicenter clinical research initiative funded by the National Institute of Mental Health (NIMH; R01 MH118514) to facilitate neuropsychology's transition to contemporary psychometric assessment methods with resultant improvement in test validation and assessment efficiency. METHOD: The NNN includes four clinical research sites (Emory University; Medical College of Wisconsin; University of California, Los Angeles (UCLA); University of Florida) and Pearson Clinical Assessment. Pearson Q-interactive (Q-i) is used for data capture for Pearson published tests; web-based data capture tools programmed by UCLA, which serves as the Coordinating Center, are employed for remaining measures. RESULTS: NNN is acquiring item-level data from 500-10,000 patients across 47 widely used Neuropsychology (NP) tests and sharing these data via the NIMH Data Archive. Modern psychometric methods (e.g., item response theory) will specify the constructs measured by different tests and determine their positive/negative predictive power regarding diagnostic outcomes and relationships to other clinical, historical, and demographic factors. The Structured History Protocol for NP (SHiP-NP) helps standardize acquisition of relevant history and self-report data. CONCLUSIONS: NNN is a proof-of-principle collaboration: by addressing logistical challenges, NNN aims to engage other clinics to create a national and ultimately an international network. The mature NNN will provide mechanisms for data aggregation enabling shared analysis and collaborative research. NNN promises ultimately to enable robust diagnostic inferences about neuropsychological test patterns and to promote the validation of novel adaptive assessment strategies that will be more efficient, more precise, and more sensitive to clinical contexts and individual/cultural differences.

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.

Interventions for ADHD in children & adolescents with epilepsy: A review and decision tree to guide clinicians.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common pediatric epilepsy comorbidities. Treating ADHD in the context of epilepsy can be overwhelming for parents and clinicians. Current frontline treatment for ADHD is stimulant medication. However, some parents of pediatric patients with epilepsy have concerns about adding additional medication to their child's epilepsy regimen and/or about adverse effects of stimulant medication. Non-medication ADHD treatments including psychosocial interventions and ketogenic diet have also shown success in improving ADHD symptoms. Our focused review provides an easy-to-use guide for clinicians on ADHD interventions and combinations of interventions for pediatric patients with epilepsy and ADHD. Our guide includes information from 8 electronic databases for peer-reviewed, English language studies of psychosocial treatments for youth with epilepsy and ADHD. One hundred eight studies were selected based on inclusion criteria (21 systematic reviews, 12 meta-analyses, 8 literature reviews, 6 population surveys, 31 clinical trials, 20 cross-sectional studies, and 10 retrospective reviews). Results indicated that stimulant medication is a frontline treatment for ADHD symptoms in youth with epilepsy, with important caveats and alternatives.

Open surgery or laser interstitial thermal therapy for low-grade epilepsy-associated tumors of the temporal lobe: A single-institution consecutive series.

Outcomes of treating low-grade epilepsy-associated tumors (LEATs) in the temporal lobe with MRI-guided laser interstitial thermal therapy (MRgLITT) remain poorly characterized. This study aimed to compare the safety and effectiveness of treating temporal lobe LEATs with MRgLITT versus open resection in a consecutive single-institution series. We reviewed all adult patients with epilepsy that underwent surgery for temporal lobe LEATs at our institution between 2002 and 2019, during which time we switched from open surgery to MRgLITT. Surgical outcome was categorized by Engel classification at >12mo follow-up and Kaplan-Meir analysis of seizure freedom. We recorded hospital length of stay, adverse events, and available neuropsychological results. Of 14 total patients, 7 underwent 9 open resections, 6 patients underwent MRgLITT alone, and 1 patient underwent an open resection followed by MRgLITT. Baseline group demographics differed and were notable for preoperative duration of epilepsy of 9.0 years (range 1-36) for open resection versus 14.0 years (range 2-34) for MRgLITT. Median length of stay was one day shorter for MRgLITT compared to open resection (p=<.0001). There were no major adverse events in the series, but there were fewer minor adverse events following MRgLITT. At 12mo follow-up, 50% (5/10) of patients undergoing open resection and 57% (4/7) of patients undergoing MRgLITT were free of disabling seizures (Engel I). When comparing patients who underwent similar procedures in the dominant temporal lobe, patients undergoing MRgLITT had fewer and milder material-specific neuropsychological declines than patients undergoing open resections. In this small series, MRgLITT was comparably safe and effective relative to open resection of temporal lobe LEATs.

Depression and Anxiety in Adult Persons With Epilepsy and Their Caregivers: A Survey-Based Study at a Tertiary Care Center.

ABSTRACT: This study evaluated the rates of depression and anxiety and their determinants in adult persons with epilepsy and their caregivers. Both completed surveys about demographic, disease-related, and psychosocial characteristics. One hundred patients and caregivers participated. A mood disorder was present in 89% of patients and 56% of caregivers. In the univariate analysis, the presence of mood disorder in the patient was associated with being unmarried, unemployed, frequent hospitalizations, side effects from polypharmacy, patient stigma, patient quality of life, caregiver anxiety, and caregiver burden. In the multivariate analysis, medication side effects sustained as an important determinant. In the univariate analysis, the presence of mood disorder in the caregiver was associated with seizure frequency, patient anxiety, patient quality of life, caregiver stigma, and caregiver burden. In the multivariate analysis, patient anxiety level and caregiver burden sustained as important determinants. Adult persons with epilepsy and their caregivers experience high rates of mood disorders, explained by certain clinical factors.

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.

Cortical disconnection in temporal lobe epilepsy.

A critical concept in neurology is cortical disconnection, in which seemingly normal gray matter can have reduced function due to loss of white matter (WM) connections. White matter damage has been extensively described in temporal lobe epilepsy (TLE), but the anatomical distribution of cortical disconnection in TLE is not fully characterized. Here, we studied 221 participants (64 left-TLE, 55 right-TLE, 102 controls) from three different epilepsy treatment centers. We employed a group connectometry diffusion imaging tractography approach to identify WM fibers with reduced integrity in TLE. We then assessed the anatomical distribution of the gray matter endpoint projections of abnormal fibers to map the anatomical pattern of disconnections. As expected, left- and right-TLE were associated with multiple WM pathways with reduced integrity, which were associated with extensive cortical disconnection involving predominantly limbic structures. Controlling for medial temporal gray matter atrophy, cortical disconnection of the left cingulum and the thalamus as well as disconnection of the bilateral putamen and the amygdala was associated with lower verbal memory immediate recall. In conclusion, our results support that cortical disconnection is an underappreciated but pervasive phenomenon in TLE, and cortical disconnection of limbic structures beyond the medial temporal regions is related to verbal memory performance.

Subjective distinguishability of seizure and non-seizure Déjà Vu: A case report, brief literature review, and research prospects.

Roughly two-thirds of all people report having experienced déjà vu-the odd feeling that a current experience is both novel and a repeat or replay of a previous, unrecalled experience. Reports of an association between déjà vu and seizure aura symptomatology have accumulated for over a century, and frequent déjà vu is also now known to be associated with focal seizures, particularly those of a medial temporal lobe (MTL) origin. A longstanding question is whether seizure-related déjà vu has the same basis and is the same subjective experience as non-seizure déjà vu. Survey research suggests that people who experience both seizure-related and non-seizure déjà vu can often subjectively distinguish between the two. We present a case of a person with a history of focal MTL seizures who reports having experienced both seizure-related and non-seizure common déjà vu, though the non-seizure type was more frequent during this person's youth than it is currently. The patient was studied with a virtual tour paradigm that has previously been shown to elicit déjà vu among non-clinical, young adult participants. The patient reported experiencing déjà vu of the common non-seizure type during the virtual tour paradigm, without associated abnormalities of the intracranial EEG. We situate this work in the context of broader ongoing projects examining the subjective correlates of seizures. The importance for memory research of virtual scenes, spatial tasks, virtual reality (VR), and this paradigm for isolating familiarity in the context of recall failure are discussed.