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Background: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions., Methods: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken., Results: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD., Conclusions: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: People with functional seizures (FS) have frequent and disabling cognitive dysfunction and mental health symptoms, with low quality of life. However, interrelationships among these constructs are poorly understood. In this meta-analysis, we examined associations between objective (i.e. performance-based) cognitive testing and self-reported (i) mental health, (ii) cognition, and (iii) quality of life in FS. Method : We searched MEDLINE, Embase, PsycINFO, and Web of Science, with the final search on June 10, 2024. Inclusion criteria were studies documenting relationships between objective cognitive test scores and self-reported (i.e. subjective) mental health, cognition, and/or quality of life in adults with FS. Exclusion criteria were mixed FS/epilepsy samples. A modified Newcastle-Ottawa Scale evaluated risk of bias. This project is registered as CRD42023392385 in PROSPERO. Results : Initially, 4,054 unique reports were identified, with the final sample including 24 articles of 1,173 people with FS. Mean age was 35.9 (SD = 3.9), mean education was 12.6 (SD = 1.3), and proportion of women was 73.9%. Risk of bias was moderate, due in part to inconsistent reporting of confounding demographic variables. Significant relationships were found between global objective cognition and global self-reported mental health ( k  = 21, Z = -0.23 [0.04], 95% CI = -0.30, -0.16), depression ( k  = 11, Z = -0.13 [0.05], 95% CI = -0.21, -0.04), cognition ( k  = 5, Z = -0.16 [0.05], 95% CI = -0.26, -0.06), and quality of life ( k  = 5, Z = -0.17 [0.05], 95% CI = -0.24, -0.10). Exploratory analyses showed associations between select cognitive and mental health constructs. Conclusions : Objective cognition is reliably associated with self-reported mental health, cognition, and quality of life in people with FS. Scientific and clinical implications are discussed.

Objective: Patients with traumatic brain injury (TBI) often present with seizures (functional and/or epileptic), but treatments for patients with TBI and seizures are limited. We examined treatment phase and 1-year post-enrollment outcomes following neurobehavioral therapy (NBT) for patients with TBI + functional seizures (FS) and TBI + epilepsy., Methods: In this multicenter, prospective, three-group, nonrandomized, controlled trial, with 1-year post-enrollment follow-up, three cohorts of adults were recruited: TBI + video-electroencephalography (EEG)-confirmed FS (n = 89), TBI + EEG-confirmed epilepsy (n = 29), and chart/history-confirmed TBI without seizures (n = 75). Exclusion criteria were recent psychotic or self-injurious behavior, current suicidal ideation, pending litigation or long-term disability, active substance use disorder, and inability to participate in study procedures. TBI + FS and TBI + epilepsy groups completed NBT for seizures, an evidence-based, 12-session, multimodal psychotherapy, whereas TBI without seizures participants received standard medical care. The primary outcome was change in seizure frequency; secondary outcomes were changes in mental health, TBI-related symptoms, disability, and quality of life., Results: Reductions in average monthly seizures occurred during treatment in TBI + FS participants (p = .002) and were significant from baseline (mean = 16.75; 95% confidence interval [CI] = 11.44-24.53) to 12 months post-enrollment (mean = 7.28, 95% CI = 4.37-12.13, p = .002, d = .38). Monthly seizures decreased during treatment in TBI + epilepsy participants (p = .002); reductions were not statistically significant from baseline (mean = 2.38, 95% CI = 1.12-5.04) to 12-month postenrollment (mean = .98, 95% CI = .40-2.42, p = .07, d = .22). Regarding treatment-phase changes in secondary outcome measures, TBI + FS participants improved significantly on 10 of 19 variables (52.6%), TBI + epilepsy participants improved on five of 19 (26.3%), and TBI-only comparisons improved on only one of 19 (5.3%)., Significance: NBT benefited patients with TBI + FS and TBI + epilepsy. Improvements were demonstrated at 1 year post-enrollment in those with TBI + FS. NBT may be a clinically useful treatment for patients with seizures., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: Epilepsy is associated with significant mortality risk. There is limited research examining how traumatic brain injury (TBI) timing affects mortality in relation to the onset of epilepsy. We aimed to assess the temporal relationship between epilepsy and TBI regarding mortality in a cohort of post-9/11 veterans., Methods: This retrospective cohort study included veterans who received health care in the Defense Health Agency and the Veterans Health Administration between 2000 and 2019. For those diagnosed with epilepsy, the index date was the date of first antiseizure medication or first seizure; we simulated the index date for those without epilepsy. We created the study groups by the index date and first documented TBI: (1) controls (no TBI, no epilepsy), (2) TBI only, (3) epilepsy only, (4) TBI before epilepsy, (5) TBI within 6 months after epilepsy, and (6) TBI >6 months after epilepsy. Kaplan-Meier estimates of all-cause mortality were calculated, and log-rank tests were used to compare unadjusted cumulative mortality rates among groups compared to controls. Cox proportional hazard models were used to compute hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: Among 938 890 veterans, 27 436 (2.92%) met epilepsy criteria, and 264 890 (28.22%) had a TBI diagnosis. Mortality was higher for veterans with epilepsy than controls (6.26% vs. 1.12%; p < .01). Veterans with TBI diagnosed ≤6 months after epilepsy had the highest mortality hazard (HR = 5.02, 95% CI = 4.21-5.99) compared to controls, followed by those with TBI before epilepsy (HR = 4.25, 95% CI = 3.89-4.58), epilepsy only (HR = 4.00, 95% CI = 3.67-4.36), and TBI >6 months after epilepsy (HR = 2.49, 95% CI = 2.17-2.85). These differences were significant across groups., Significance: TBI timing relative to epilepsy affects time to mortality; TBI within 6 months after epilepsy or before epilepsy diagnosis was associated with earlier time to death compared to those with epilepsy only or TBI >6 months after epilepsy., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: Functional neurological symptom disorder (FNSD) is a neuropsychiatric condition characterized by signs/symptoms associated with brain network dysfunction. FNSDs are common and are associated with high healthcare costs. FNSDs are relevant to neuropsychologists, as they frequently present with chronic neuropsychiatric symptoms, subjective cognitive concerns, and/or low neuropsychological test scores, with associated disability and reduced quality of life. However, neuropsychologists in some settings are not involved in care of patients with FNSDs. This review summarizes relevant FNSD literature with a focus on the role of neuropsychologists., Methods: A brief review of the literature is provided with respect to epidemiology, public health impact, symptomatology, pathophysiology, and treatment., Results: Two primary areas of focus for this review are the following: (1) increasing neuropsychologists' training in FNSDs, and (2) increasing neuropsychologists' role in assessment and treatment of FNSD patients., Conclusions: Patients with FNSD would benefit from increased involvement of neuropsychologists in their care.

Background: Cognition is a core component of functional seizures, but the literature on cognition in this disorder has been heterogeneous, with no clear unifying profile emerging from individual studies. The aim of this study was to do a systematic review and meta-analysis of cognitive performance in adults with functional seizures compared with epilepsy (including left temporal lobe epilepsy) and compared with healthy non-seizure cohorts., Methods: In this systematic review and meta-analysis, starting Feb 6, 2023, replicated and updated on Oct 31, 2023, a medical librarian searched MEDLINE, Embase, PsycINFO, and Web of Science. Inclusion criteria were full reports documenting raw or standardised cognitive test data in adults with functional seizures compared with adults with epilepsy, prospectively recruited healthy comparisons, or published norms. Grey literature was retained and there were no language or date restrictions. We excluded studies only reporting on mixed functional seizures and epilepsy, or mixed functional neurological samples, with no pure functional seizures group. Risk of bias was evaluated using a modified version of the Newcastle-Ottawa Scale. People with lived experiences were not involved in the design or execution of this study. This study is registered as CRD42023392385 in PROSPERO., Findings: Of 3834 records initially identified, 84 articles were retained, including 8654 participants (functional seizures 4193, epilepsy 3638, and healthy comparisons 823). Mean age was 36 years (SD 12) for functional seizures, 36 years (12) for epilepsy, and 34 years (10) for healthy comparisons, and the proportion of women per group was 72% (range 18-100) for functional seizures, 59% (range 15-100) for epilepsy, and 69% (range 34-100) for healthy comparisons. Data on race or ethnicity were rarely reported in the individual studies. Risk of bias was moderate. Cognitive performance was better in people with functional seizures than those with epilepsy (Hedges' g=0·17 [95% CI 0·10-0·25)], p<0·0001), with moderate-to-high heterogeneity (Q[56]=128·91, p=0·0001, I 2 =57%). The functional seizures group performed better than the epilepsy group on global cognition and intelligence quotient (g=0·15 [0·02-0·28], p=0·022) and language (g=0·28 [0·14-0·43], p=0·0001), but not other cognitive domains. A larger effect was noted in language tests when comparing functional seizures with left temporal lobe epilepsy (k=5; g=0·51 [0·10 to 0·91], p=0·015). The functional seizures group underperformed relative to healthy comparisons (g=-0·61 [-0·78 to -0·44], p<0·0001), with significant differences in all cognitive domains. Meta regressions examining effects of multiple covariates on global cognition were not significant., Interpretation: Patients with functional seizures have widespread cognitive impairments that are likely to be clinically meaningful on the basis of moderate effect sizes in multiple domains. These deficits might be slightly less severe than those seen in many patients with epilepsy but nevertheless argue for consideration of clinical assessment and treatment., Funding: Department of Veterans Affairs, Veterans Health Administration., Competing Interests: Declaration of interests RVP receives funding from VA Providence, RR&D Center for Neurorestoration and Neurotechnology; engages in profit sharing with the International Neuropsychological Society for Continuing Education proceeds from the Navigating Neuropsychology podcast; receives royalties from publication of the book, Becoming a Neuropsychologist: Advice and Guidance for Students and Trainees (Springer, 2021); receives travel support from Brown University Department of Psychiatry and Human Behavior; is a member of the advisory board for the New2Neuropsychology organisation; and the research reported or outlined here was supported by the Department of Veterans Affairs, Veterans Health Administration, VISN 1 Career Development Award to R Van Patten. TAA is supported by a Career Development Award (1IK2RX004764) from the VA Rehabilitation Research and Development Service. EC receives grant funding from the Women's Board of Northwestern University, and is on the Medical Advisory Board for the Epilepsy Foundation of Chicago. JAB engages in profit sharing with the International Neuropsychological Society for Continuing Education proceeds from the Navigating Neuropsychology podcast; receives royalties from publication of the book, Becoming a Neuropsychologist: Advice and Guidance for Students and Trainees (Springer, 2021); and is a member of the Advisory Board for the New2Neuropsychology organisation. HA has received research funding from National Institutes of Health, Department of Defense Congressionally Directed Medical Research Program Epilepsy Research Program, The Epilepsy Consortium, Eisai, UCB, and Cerevel. SC is a co-investigator for the National Institute of Mental Health U01 MH 123427 study, “Low intensity focused ultrasound: A new paradigm for depression and anxiety”. EWT gratefully acknowledges the support of a VA Rehabilitation Research and Development Research Career Scientist Award. WCL has served on the editorial boards of Epilepsia, Epilepsy & Behavior, Journal of Neurology, Neurosurgery and Psychiatry, and Journal of Neuropsychiatry and Clinical Neurosciences; receives funding from the DoD CDMRP Epilepsy Research Program (W81XWH-17-0169, PI), co-editor royalties for Gates and Rowan's Nonepileptic Seizures, and co-author royalties from Oxford University Press for Taking Control of Your Seizures: Workbook and for Treating Nonepileptic Seizures: Therapist Guide; serves on the Epilepsy Foundation New England Professional Advisory Board; received honoraria for the American Academy of Neurology Meeting Annual Course; served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, SpectrumHealth, Emory University, Oregon Health Sciences University, and Vanderbilt University; and provided medicolegal expert witness testimony. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Traumatic brain injury (TBI) often precedes the onset of epileptic (ES) or psychogenic nonepileptic seizures (PNES) with depression being a common comorbidity. The relationship between depression severity and quality of life (QOL) may be related to resting-state network complexity. We investigated these relationships in adults with TBI-only, TBI + ES, or TBI + PNES using Sample Entropy (SampEn), a measure of physiologic signals complexity., Methods: Adults with TBI-only (n = 60), TBI + ES (n = 21), or TBI + PNES (n = 56) completed the Beck Depression Inventory-II (BDI-II; depression symptom severity) and QOL in Epilepsy (QOLIE-31) assessments and underwent resting-state functional magnetic resonance imaging (rs-fMRI). SampEn values derived from six resting state functional networks were calculated per participant. Effects of group, network, and group-by-network-interactions for SampEn were investigated with a mixed-effects model. We examined relationships between BDI-II, QOL, and SampEn of each of the networks., Results: Groups did not differ in age, but there was a higher proportion of women with TBI + PNES (p = 0.040). TBI + ES and TBI-only groups did not differ in BDI-II or QOLIE-31 scores, while the TBI + PNES group scored worse on both measures. The fixed effects of the model revealed significant differences in SampEn values across networks (lower SampEn for the frontoparietal network compared to other networks). The likelihood ratio test for group-by-network-interactions was significant (p = 0.033). BDI-II was significantly negatively associated with Overall QOL scale scores in all groups, and significantly negatively associated with network SampEn values only in the TBI + PNES group., Significance: Only TBI + PNES had significant relationships between depression symptom severity and network SampEn values indicating that the resting state network complexity is related to depression severity in this group but not in TBI + ES or TBI-only., Plain Language Summary: The brain has a complex network of internal connections. How well these connections work may be affected by TBI and seizures and may underlie mental health symptoms including depression; the worse the depression, the worse the quality of life. Our study compared brain organization in people with TBI, people with epilepsy after TBI, and people with nonepileptic seizures after TBI. Only people with nonepileptic seizures after TBI showed a relationship between how organized their brain connections were and how bad was their depression. We need to better understand these relationships to develop more impactful, effective treatments., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: The uncinate fasciculus (UF) has been implicated previously in contributing to the pathophysiology of functional (nonepileptic) seizures (FS). FS are frequently preceded by adverse life events (ALEs) and present with comorbid psychiatric symptoms, yet neurobiological correlates of these factors remain unclear. To address this gap, using advanced diffusion magnetic resonance imaging (dMRI), UF tracts in a large cohort of patients with FS and pre-existing traumatic brain injury (TBI + FS) were compared to those in patients with TBI without FS (TBI-only). We hypothesized that dMRI measures in UF structural connectivity would reveal UF differences when controlling for TBI status. Partial correlation tests assessed the potential relationships with psychiatric symptom severity measures., Methods: Participants with TBI-only (N = 46) and TBI + FS (N = 55) completed a series of symptom questionnaires and MRI scanning. Deterministic tractography via diffusion spectrum imaging (DSI) was implemented in DSI studio (https://dsi-studio.labsolver.org) with q-space diffeomorphic reconstruction (QSDR), streamline production, and manual segmentation to assess bilateral UF integrity. Fractional anisotropy (FA), radial diffusivity (RD), streamline counts, and their respective asymmetry indices (AIs) served as estimates of white matter integrity., Results: Compared to TBI-only, TBI + FS participants demonstrated decreased left hemisphere FA and RD asymmetry index (AI) for UF tracts (both p < .05, false discovery rate [FDR] corrected). Additionally, TBI + FS reported higher symptom severity in depression, anxiety, and PTSD measures (all p < .01). Correlation tests comparing UF white matter integrity differences to psychiatric symptom severity failed to reach criteria for significance (all p > .05, FDR corrected)., Significance: In a large, well-characterized sample, participants with FS had decreased white matter health after controlling for the history of TBI. Planned follow-up analysis found no evidence to suggest that UF connectivity measures are a feature of group differences in mood or anxiety comorbidities for FS. These findings suggest that frontolimbic structural connectivity may play a role in FS symptomology, after accounting for prior ALEs and comorbid psychopathology severity., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Competing Interests: W.C.L. receives editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures , 3rd ed. (Cambridge University Press, 2010) and 4th ed. (2018), plus author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015). The remaining authors declare no conflicts of interest.

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.L.P. has received honoraria for continuing medical education lectures in FND; royalties from Springer for the textbook Functional Movement Disorder and from Elsevier for the textbook Functional Neurological Disorder; is on the editorial boards of Brain and Behavior (paid), Epilepsy & Behavior, and The Journal of Neuropsychiatry and Clinical Neurosciences; has received funding from the NIH and Sidney R. Baer Jr. Foundation for FND research; and is on the FND Society board and American Neuropsychiatric Association advisory council. T.R.N. does expert witness work in personal injury and clinical negligence cases of FND and other disorders; has received financial support for lectures from the FND Society; receives royalties from CRC Press for The Pocket Prescriber textbook series and from Springer for the textbook Functional Movement Disorder; has received grant funding, including for studies related to FND, from the UK National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC); is co-chair of the FNDS patient liaison committee and on the medical advisory boards of the charities FND Hope UK and FND Action and a trustee of FND Action. A.A.A.P. honoraria from Cobel Daruo; royalty: Oxford University Press (Book publication). M.B. receives royalties from CRC Press for Pocket Prescriber Psychiatry 2E and has been awarded fellowships from NIHR and the Wellcome Trust for studies on FND. A.J.C. paid associate editor of Journal of Neurology, Neurosurgery and Psychiatry; provides expert testimony in court on a range of neuropsychiatric topics including FND; and is on the FND Society board. Q.D. does medical expert reporting in personal injury and clinical negligence cases, including in cases of FND. M.J.E. does medical expert reporting in personal injury and clinical negligence cases, including in cases of FND; has shares in Brain & Mind (which provides neuropsychiatric and neurological rehabilitation in the independent medical sector, including in people with FND); has received financial support for lectures from the International Parkinson’s and Movement Disorders Society and the FND Society; receives royalties from Oxford University Press for his book The Oxford Specialist Handbook of Parkinson’s Disease and Other Movement Disorder; has received honoraria for medical advice to Teva Pharmaceuticals; receives grant funding, including for studies related to FND, from the National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC); is an associate editor of the European Journal of Neurology; is a member of the international executive committee of the International Parkinson’s and Movement Disorders Society and the FND Society board; and is on the medical advisory boards of the charities FND Hope UK and Dystonia UK. A.J.E. has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Neuroderm, Amneal, Acadia, Avion Pharmaceuticals, Acorda, Kyowa Kirin, Supernus (formerly, USWorldMeds), and Herantis Pharma; honoraria for speakership for Avion, Amneal, and Supernus; royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; cofounded REGAIN Therapeutics; co-inventor of the patent “Compositions and methods for treatment and/or prophylaxis of proteinopathies”; and is on the FND Society board. M.H. is an inventor of a patent held by NIH for the H-coil for magnetic stimulation for which he receives license fee payments from the NIH (from Brainsway); is on the Medical Advisory Boards of Brainsway, QuantalX, and VoxNeuro; has consulted for Janssen Pharmaceuticals, and is on the FND Society board. R.A.A.K. receives royalties from Guilford press for a book chapter related to FND; grant funding from the National Health and Medical Research Council, The Medical Research Future Fund for research in FND; provides expert medico-legal opinions on neuropsychiatric disorders, including FND; is on the board of the International Neuropsychiatry Association. M.A.J.T reports grants from the Netherlands Organization for Health Research and Development ZonMW Topsubsidie (91218013) and ZonMW Program Translational Research(40–44600-98–323); has received a European Fund for Regional Development from the European Union (01492947) and a European Joint Programme on Rare Diseases (EJP RD) Networking Support Scheme; furthermore, from the province of Friesland, the Stichting Wetenschapsfonds Dystonie and unrestricted grants from Actelion, Ipsen and Merz. W.C.L. has served on the editorial boards of Epilepsia, Epilepsy & Behavior; Journal of Neurology, Neurosurgery and Psychiatry, and The Journal of Neuropsychiatry and Clinical Neurosciences; receives editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures, 3rd ed. (Cambridge University Press, 2010) and 4th ed. (2018); author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); has received research support from the Department of Defense (DoD W81XWH-17–0169), NIH (NINDS 5K23NS45902 [PI]), VA Providence HCS, Center for Neurorestoration and Neurorehabilitation, Rhode Island Hospital, the American Epilepsy Society (AES), the Epilepsy Foundation (EF), Brown University and the Siravo Foundation; has served on the Epilepsy Foundation New England Professional Advisory Board, the FND Society Board, the American Neuropsychiatric Association advisory council; has received honoraria for the AES Annual Meeting; has served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health, Emory University, Oregon Health Sciences University and Vanderbilt University; and has provided medico legal expert testimony. C.W.M. has received honoraria for continuing medical education lectures in FND, royalties from Springer for a textbook on functional movement disorder, and has received grant support from the Parkinson’s Foundation, Alzheimer’s Association and the Stony Brook Biomedical Sciences Innovation Fund unrelated to this work. J. P. Staab is supported by grant W81XWH1810760 from the US Department of Defense. J.S. royalties from UpToDate and carries out expert witness work in relation to FND; runs a free website for people with FND, www.neurosymptoms.org; and is on the FND Society board. J.P. Szaflarski, funding: NIH, NSF, DoD, Shor Foundation for Epilepsy Research, UCB Biosciences, NeuroPace Inc., SAGE Therapeutics Inc., Serina Therapeutics Inc., LivaNova Inc., Greenwich Biosciences Inc., Biogen Inc., Eisai Inc., State of AL; Consulting/Advisory Boards: PureTech Health, Biopharmaceutical Research Company, LivaNova Inc., UCB Pharma, AdCel Pharma, iFovea Inc; Editor-in-Chief, Epilepsy & Behavior Reports (paid); Editorial board member for Epilepsy & Behavior, Journal of Epileptology (associate editor), Journal of Medical Science, and Folia Medica Copernicana; provided expert opinion in medico-legal cases including of FND; has served on the Alabama State Medical Cannabis Study Commission (nominated by Gov. Ivey); serves on the Alabama Medical Cannabis Commission (2021–2025; nominated by Dr. Scott Harris, State Health Officer). S.A. is on the FND Society board.

Background and Objectives: Traumatic brain injury (TBI) is a well-established epilepsy risk factor and is common among service members. Deployment-related TBI, where combat/blast may be more common, may have different outcomes than nondeployment-related TBI. This work examined associations of all TBI exposures (not just combat), and epilepsy, while adjusting for comorbidities associated with epilepsy, among veterans by deployment status., Methods: The cohort included post-9/11 veterans with ≥2 years of care in both Veterans Health Administration and Defense Health Agency systems. We identified epilepsy using ICD-9/10-CM codes, antiseizure medication, and service-connected disability for epilepsy. We conducted a logistic regression model with interaction terms for conditions by deployment history that adjusted for demographics and military characteristics., Results: The cohort (n = 938,890) included post-9/11 veterans of whom 27,436 (2.92%) had epilepsy. Most veterans had a history of deployment (70.64%), referred to as "deployed." Epilepsy was more common among veterans who were never deployed ("nondeployed") (3.85% vs 2.54%). Deployed veterans were more likely to have had TBI, compared with the nondeployed veterans (33.94% vs 14.24%), but nondeployed veterans with moderate/severe TBI had higher odds of epilepsy compared with deployed veterans (adjusted odds ratio [aOR] 2.92, 95% CI 2.68-3.17 vs aOR 2.01, 95% CI 1.91-2.11). Penetrating TBI had higher odds of epilepsy among the deployed veterans (aOR 5.33, 95% CI 4.89-5.81), whereas the odds of epilepsy for mild TBI did not significantly differ by deployment status. Although most neurologic conditions were more prevalent among the nondeployed veterans, they were often associated with higher odds of epilepsy in the deployed veterans., Discussion: Deployment history had a significant differential impact on epilepsy predictors. As expected, penetrating TBI had a greater epilepsy impact among deployed veterans perhaps due to combat/blast. Some epilepsy predictors (moderate/severe TBI, multiple sclerosis, and Parkinson disease) had a stronger association in the nondeployed veterans suggesting a potential healthy warrior effect in which such conditions preclude deployment. Other neurologic conditions (e.g., brain tumor, Alzheimer disease/frontotemporal dementia) had a greater epilepsy impact in the deployed veterans. This may be attributable to deployment-related exposures (combat injury, occupational exposures). A better understanding of deployment effects is critical to provide targeted epilepsy prevention in veterans and military service members.

Background and Purpose: The aim of this study was to assess the repeatability of neurite orientation dispersion and density imaging in healthy controls (HCs) and traumatic brain injury (TBI)., Methods: Seventeen HCs and 48 TBI patients were scanned twice over 18 weeks with diffusion imaging. Orientation dispersion (ODI), neurite density (NDI), and the fraction of isotropic diffusion (F-ISO) were quantified in regions of interest (ROIs) from a gray matter, subcortical, and white matter atlas and compared using the coefficient of variation for repeated measures (CV rep ), which quantifies the expected percent change on repeated measurement. We used a modified signed likelihood ratio test (M-SLRT) to compare the CV rep between groups in each ROI while correcting for multiple comparisons., Results: NDI exhibited excellent repeatability in both groups; the only group difference was found in the fusiform gyrus, where HCs exhibited better repeatability (M-SLRT = 9.463, p = .0021). ODI also had excellent repeatability in both groups, although repeatability was significantly better in HCs in 16 cortical ROIs (p < .0022) and in the bilateral white matter and bilateral cortex (p < .0027). F-ISO exhibited relatively poor repeatability in both groups, with few group differences., Conclusion: Overall, the repeatability of the NDI, ODI, and F-ISO metrics over an 18-week period is acceptable for assessing the effects of behavioral or pharmacological interventions, though caution is advised when assessing F-ISO changes over time., (© 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Cognitive functioning impacts clinical symptoms, treatment response, and quality of life in adults with functional/nonepileptic seizures (FS/NES), but no study to date examines effects of behavioral FS/NES treatment on cognition in these patients. We hypothesized that there would be a reduction in cognitive symptoms in participants with FS/NES and traumatic brain injury (TBI) following neurobehavioral therapy (NBT). We also hypothesized that select seizure-related, medication, subjective cognitive, and mental health symptoms would be negatively correlated with improvements in cognitive performance after NBT. Participants were 37 adults with TBI + FS/NES and 35 adults with TBI only, recruited from medical centers in the northeastern or southeastern U.S. TBI + FS/NES participants completed a 12 session NBT intervention, and TBI without seizures participants were not treated. All participants completed pre-post assessments of cognition (Montreal Cognitive Assessment [MoCA]) and baseline sociodemographic factors and mental health symptoms. Pre-post MoCA scores increased significantly in TBI + FS/NES participants (28/37 [75.7%] improved) but not in TBI comparisons (10/35 [28.6%] improved). Language, memory, and visuospatial/executive functions, but not attention, improved over time in the TBI + FS/NES group. Gains in cognition were concentrated in those TBI + FS/NES participants with likely baseline cognitive impairments (MoCA total score <26), and 9/17 of these participants moved from the "impaired" range at baseline (<26) to the "intact" range at endpoint (≥26). Lastly, participants taking fewer medications and reporting lower subjective cognitive difficulties at baseline showed larger pre-post MoCA total score improvements. Overall, results from this study suggest the potential for positive change in cognition in FS/NES and co-occurring TBI using evidence-based psychotherapy., Competing Interests: Declaration of competing interest Dr. Ryan Van Patten receives funding from VA Providence, RR&D Center for Neurorestoration and Neurotechnology. He engages in profit sharing with the International Neuropsychological Society for Continuing Education proceeds from the Navigating Neuropsychology podcast. He also receives royalties from publication of the book, Becoming a Neuropsychologist: Advice and Guidance for Students and Trainees (Springer, 2021). Dr. Tyler Gaston receives a consulting fee from GW Biosciences, honorarium from the American Academy of Neurology. Dr. A. M. Goodman is funded by US Department of Defense grant W81XWH-17-1-0619 and NIH grant (R01HD102723). Dr. L. E. Grayson has received research support from the Department of Defense (DoD W81XWH-17-0169) and the State of Alabama. She serves on the Board of the Epilepsy Foundation of Western North Carolina and is receiving consulting fees from Jazz Pharmaceuticals. A.M. Goodman is funded by US Department of Defense grant W81XWH-17-1-0619 and NIH grants (R01HD102723 and R21MH133055-01 [PI]). S. Correia is a Co-Investigator for the NIMH U01 MH 123427 study, “Low intensity focused ultrasound: A new paradigm for depression and anxiety.” J.B. Allendorfer is funded by the U.S. Department of Defense (W81XWH-17-1-0619), the state of Alabama Carlys Law, the Evelyn F. McKnight Brain Institute at UAB, and NIH (R01HD102723 [PI]), and has served as a consultant for LivaNova Inc. Dr. J. P. Szaflarski: • Funding: NIH, NSF, DoD, State of Alabama, Shor Foundation for Epilepsy Research, UCB Pharma Inc., NeuroPace Inc., Greenwich Biosciences Inc., Biogen Inc., Xenon Pharmaceuticals, Serina Therapeutics Inc., and Eisai, Inc. • Consulting/Advisory Boards: Greenwich Biosciences Inc., Pure Tech Health Inc., NeuroPace, Inc., Serina Therapeutics Inc., AdCel Biopharma Inc., iFovea Inc, LivaNova Inc., UCB Pharma Inc., SK Lifesciences Inc., and medico-legal services. • Paid Editorial Work: Editor-in-Chief – Epilepsy & Behavior Reports. • Dr. Szaflarski has served as a member on the Alabama State Medical Cannabis Study Commission (nominated by Gov. Ivey). • Dr. Szaflarski serves on the Alabama Medical Cannabis Commission (2021–2025; nominated by Dr. Scott Harris, State Health Officer). Dr. W. Curt LaFrance Jr. receives funding from the DoD, and co-author royalties from Oxford University Press for Taking Control of Your Seizures: Workbook and for Treating Nonepileptic Seizures: Therapist Guide. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objective: We aimed to prospectively quantify changes in white matter morphology after neurobehavioral therapy (NBT) for functional seizures (FS) using neurite orientation dispersion and density imaging (NODDI). We hypothesized that patients with FS would exhibit white matter plasticity in the uncinate fasciculus, fornix/stria terminalis, cingulum, and corticospinal tract following NBT that would correlate with improvements in affective symptoms, postconcussive symptoms, and quality of life (QOL)., Methods: Forty-two patients with traumatic brain injury (TBI) and FS (TBI+FS) underwent NBT and provided pre-/postintervention neuroimaging and behavioral data; 47 controls with TBI without FS (TBI-only) completed the same measures but did not receive NBT. Changes in neurite density, orientation dispersion (orientation dispersion index [ODI]), and extracellular free water (FW) were compared between groups., Results: Significant ODI increases in the left uncinate fasciculus in TBI+FS (mean difference = 0.017, p = 0.039) correlated with improvements in posttraumatic symptoms (r = -0.395, p = 0.013), QOL (r = 0.474, p = 0.002), emotional well-being (r = 0.524, p < 0.001), and energy (r = 0.474, p = 0.002). In TBI-only, ODI decreased (mean difference = -0.008, p = 0.047) and FW increased (mean difference = 0.011, p = 0.003) in the right cingulum. FW increases correlated with increased psychological problems (r = 0.383, p = 0.013). In TBI+FS, NBT resulted in FS decreases of 3.5 seizures per week. None of the imaging changes correlated with FS frequency., Interpretation: We identified white matter changes after NBT in patients with FS that were associated with improved psychosocial functioning. NODDI could be incorporated into future mechanistic assessments of interventions in patients with FS. ANN NEUROL 2023;94:350-365., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Mental health comorbidities are prevalent and problematic in patients with seizures but often suboptimally managed. To address common gaps in care, the Integrated Mental Health Care Pathways Task Force of the International League Against Epilepsy (ILAE) Psychiatry Commission was tasked with providing education and guidance on the integration of mental health management (e.g., screening, referral, treatment) into routine seizure care. This report aims to describe a variety of established services in this area, with a specific focus on psychological care models. Services were identified by members of the ILAE Psychiatry Commission and authors of psychological intervention trials in epilepsy. A total of eight services met inclusion criteria and agreed to be showcased. They include three pediatric and five adult services located across four distinct ILAE regions (Europe, North America, Africa, Asia Oceania). The report describes the core operations, known outcomes, and implementation factors (i.e., barriers and facilitators) of these services. The report concludes with a set of practical tips for building successful psychological care services within seizure settings, including the importance of having local champions, clearly defining the scope of the service, and establishing sustainable funding models. The breadth of exemplars demonstrates how models tailored to the local environment and resources can be implemented. This report is an initial step to disseminate information regarding integrated mental health care within seizure care settings. Future work is needed to systematically examine both psychological and pharmacological care models and to further establish the evidence base in this area, especially around clinical impact, and cost-effectiveness., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Patients with functional neurological (conversion) disorder (FND) have historically been difficult to treat. Outcomes have been studied in research trials, documenting improvements; however, limited information is available from a community-treated FND cohort., Objectives: We aimed to examine clinical outcomes in outpatients with FND treated with the Neuro-Behavioral Therapy (NBT) approach. These uncontrolled setting treatment data could complement more structured clinical studies results., Methods: We conducted a retrospective chart review of consecutive patients diagnosed with FND, ages 17 to 75, who were treated with the NBT workbook at the Rhode Island Hospital Behavioral Health clinic between 2014 and 2022. NBT consisted of 45-minute, individual, outpatient sessions, in clinic or via telehealth with one clinician. Global Assessment of Functioning (GAF), and Clinical Global Impression (CGI) -Severity, and -Improvement were scored for every appointment., Results: Baseline characteristics are available for 107 patients. Mean age at FND symptom onset was 37 years. Patients had a mix of FND semiologies, which included Psychogenic Nonepileptic Seizures (71%), Functional Movement Disorder (24.3%), Functional Sensory Disorder (14%), Functional Weakness (6.5%), and Functional Speech Disorder (5.6%). Clinical evaluation scores revealed improvements over time., Conclusions: We describe a well-characterized sample of patients with various and mixed FND semiologies, who received manualized therapy, NBT, in an outpatient clinic. Patients had similar psychosocial profiles to those in clinical studies and displayed improvement in clinical measures. These results demonstrate the practicability of NBT for motor FND semiologies and for PNES, in a "real-world" outpatient practice, extending care beyond structured clinical trials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: as noted in disclosures., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Traumatic brain injury (TBI) may precipitate the onset of functional seizures (FSs). Many patients with FS report at least one prior TBI, and these patients typically present with more severe psychiatric comorbidities. TBI and psychopathology are linked to changes in neural network connectivity, but their combined effects on these networks and relationship to the effects of FS remain unclear. We hypothesised that resting-state functional connectivity (rsFC) would differ between patients with FS and TBI (FS+TBI) compared with TBI without FS (TBI only), with variability only partially explained by the presence of psychopathology., Methods: Patients with FS+TBI (n=52) and TBI only (n=54) were matched for age and sex. All participants completed psychiatric assessments prior to resting-state functional MRI at 3 T. Independent component analysis identified five canonical rsFC networks related to emotion and motor functions., Results: Five linear mixed-effects analyses identified clusters of connectivity coefficients that differed between groups within the posterior cingulate of the default mode network, insula and supramarginal gyrus of the executive control network and bilateral anterior cingulate of the salience network (all α=0.05, corrected). Cluster signal extractions revealed decreased contributions to each network for FS+TBI compared to TBI only. Planned secondary analyses demonstrated correlations between signal and severity of mood, anxiety, somatisation and global functioning symptoms., Conclusions: These findings indicate the presence of aberrant connectivity in FS and extend the biopsychosocial network model by demonstrating that common aetiology is linked to both FS and comorbidities, but the overlap in affected networks varies by comorbid symptoms., Competing Interests: Competing interests: AMG was funded by US Department of Defense (grant W81XWH-17-1-0619) and National Institutes of Health (NIH) (grant R01HD102723). RN, SC, PK has no conflicts to report. NSP received clinical trial support from Wave Neuro and Neurolief through Veterans Affairs contracts. JBA was funded by the US Department of Defense (W81XWH-17-1-0619), the state of Alabama 'Carly’s Law', the Evelyn F. McKnight Brain Institute at University of Alabama at Birmingham and NIH (R01HD102723 (PI)) and has served as a consultant for LivaNova Inc. WCL Jr. Dr. LaFrance served on the editorial boards of Epilepsia, Epilepsy & Behavior; Journal of Neurology, Neurosurgery and Psychiatry, and Journal of Neuropsychiatry and Clinical Neurosciences; received editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures, 3rd ed. (Cambridge University Press, 2010) and 4th ed. (2018); received author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); received research support from the Department of Defense (DoD W81XWH-17-0169), NIH (NINDS 5K23NS45902 (PI)), Providence VAMC, Center for Neurorestoration and Neurotechnology, Rhode Island Hospital, the American Epilepsy Society, the Epilepsy Foundation, Brown University and the Siravo Foundation; served on the Epilepsy Foundation New England Professional Advisory Board, the Functional Neurological Disorder Society Board of Directors and the American Neuropsychiatric Association Advisory Council; received honoraria for the American Academy of Neurology Annual Meeting; served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health, Emory University, Oregon Health Sciences University and Vanderbilt University; and provided medicolegal expert testimony. JPS is funded by NIH, NSF, DoD, State of Alabama, Shor Foundation for Epilepsy Research, UCB Pharma, NeuroPace, Greenwich Biosciences, Biogen, Xenon Pharmaceuticals and Serina Therapeutics; served on consulting/advisory boards for Greenwich Biosciences, NeuroPace, Serina Therapeutics, LivaNova, UCB Pharma, iFovea, AdCel Biopharma LLC, and Elite Medical Experts LLC and served as an editorial board member for Epilepsy & Behavior, Journal of Epileptology (associate editor), Epilepsy & Behavior Reports (associate editor), Journal of Medical Science, Epilepsy Currents (contributing editor) and Folia Medica Copernicana., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with psychogenic nonepileptic seizures (PNES) represent a distinct, challenging group among those with functional neurologic symptom (conversion) disorders and involve a complex set of symptoms and comorbidities, best evaluated and treated by a multidisciplinary team of clinicians. Multidisciplinary, collaborative care is becoming more common, using evidence-based treatment. Outpatient neurology clinics at sites not currently treating these patients hold potential for providing such a model of care, with coordination of services. Best practice care should encourage the integration of neurology and mental health professionals to improve communication among clinicians and with patients, allowing for better patient care and symptomatic outcomes., Competing Interests: Disclosure N.J. Beimer has served as an ad hoc reviewer for Epilepsy & Behavior; has received honoraria from MedLink LLC and Decker Intellectual Properties; has received research support from the Health Resources and Services Administration (HRSA H98MC30374, co-I), NIH (R01 NS094399-10, co-I), the University of Michigan Department of Neurology, and the Pediatric Epilepsy Research Foundation; serves on the Epilepsy Foundation of Michigan Professional Advisory Board, and has provided medicolegal expert testimony. W.C. LaFrance, Jr. has served on the editorial boards of Epilepsia, Epilepsy & Behavior; Journal of Neurology, Neurosurgery and Psychiatry, and Journal of Neuropsychiatry and Clinical Neurosciences; receives editor's royalties from the publication of Gates and Rowan's Nonepileptic Seizures, 3rd edition (Cambridge University Press, 2010) and 4th ed (2018); author's royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); has received research support from the Department of Defense (DoD WSlXWH-17-0169), NIH (NINDS 5K23NS45902 [PI]), Providence VAMC, Center for Neurorestoration and Neurotechnology, Rhode Island Hospital, the American Epilepsy Society (AES), the Epilepsy Foundation (EF), Brown University, and the Siravo Foundation; serves on the Epilepsy Foundation New England Professional Advisory Board, the Functional Neurological Disorder Society Board of Directors, the American Neuropsychiatric Association Advisory Council; has received honoraria for the American Academy of Neurology and AES Annual Meetings; has served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health, Emory University, Oregon Health Sciences University, and Vanderbilt University; and has provided medicolegal expert testimony., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: In patients with functional seizures (FS), delay in diagnosis (DD) may negatively affect outcomes. Altered brain responses to emotional stimuli have been shown in adults with FS. We hypothesized that DD would be associated with differential fMRI activation in emotion processing circuits., Methods: Fifty-two adults (38 females) with video-EEG confirmed FS prospectively completed assessments related to symptoms of depression (BDI-II), anxiety (BAI), post-traumatic stress disorder (PCL-S), a measure of how their symptoms affect day-to-day life (GAF), and fMRI at 3T with emotional faces task (EFT). During fMRI, subjects indicated "male" or "female" via button press while implicitly processing happy, sad, fearful, and neutral faces. Functional magnetic resonance imaging (FMRI) response to each emotion was modeled and group analyses were performed in AFNI within pre-specified regions-of-interest involved in emotion processing. A median split (507 days) defined short- (s-DD) and long-delay diagnosis (l-DD) groups. Voxelwise regression analyses were also performed to examine linear relationship between DD and emotion processing. FMRI signal was extracted from clusters showing group differences and Spearman's correlations assessed relationships with symptom scores., Results: Groups did not differ in FS age of onset, sex distribution, years of education, TBI characteristics, EFT in-scanner or post-test performance, or scores on the GAF, BDI-II, BAI, and PCL-S measures. The s-DD group was younger than l-DD (mean age 32.6 vs. 40.1; p = 0.022) at the time of study participation. After correcting for age, compared to s-DD, the l-DD group showed greater fMRI activation to sad faces in the bilateral posterior cingulate cortex (PCC) and to neutral faces in the right anterior insula. Within-group linear regression revealed that with increasing DD, there was increased fMRI activation to sad faces in the PCC and to happy faces in the right anterior insula/inferior frontal gyrus (AI/IFG). There were positive correlations between PCC response to sad faces and BDI-II scores in the l-DD group (rho = 0.48, p = 0.012) and the combined sample (rho = 0.30, p = 0.029). Increased PCC activation to sad faces in those in the l-DD group was associated with worse symptoms of depression (i.e. higher BDI-II score)., Conclusions: Delay in FS diagnosis is associated with fMRI changes in PCC and AI/IFG. As part of the default mode network, PCC is implicated in mood control, self-referencing, and other emotion-relevant processes. In our study, PCC changes are linked to depression. Future studies should assess the effects of interventions on these abnormalities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Managing one's own symptoms, medications, treatments, lifestyle, and psychological and social aspects of chronic disease is known as self-management. The Institute of Medicine has identified three categories of epilepsy self-management, including medication management, behavior management, and emotional support. Overall, there has been limited research of interventions measuring epilepsy self-management behaviors. The present study aimed to develop an abbreviated version of the full, previously published, Adult Epilepsy Self-Management Measurement Instrument (AESMMI) using confirmatory factor analysis. Data come from a cross-sectional survey of people with epilepsy. The sample included adults with epilepsy (n = 422), who reported that a clinician diagnosed them with epilepsy or a seizure disorder. We ran confirmatory factor analyses in testing the abbreviated scale. The scale was reduced using a theory-driven data-informed approach. The full AESMMI length was reduced by 40% (from 65 to 38 items) with an overall internal consistency of 0.912. The abbreviated AESMMI retained the 11 subdomains, with Cronbach's alphas from 0.535 to 0.878. This reduced item scale can be useful for assessing self-management behaviors for people with epilepsy or measuring outcomes in self-management research., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Despite providing care for patients with "disturbances of the same organ," the brain, the therapeutic approaches used by neurologists and psychiatrists are, to some extent, distinct. With recognition of the closely coupled relationship between physical health and mental health, there is increased awareness of the need to provide an integrated, neuropsychiatric approach to the care of patients in neurology. In this review article, we provide a broad overview of how neurologists can use psychotherapeutic principles to enhance patient-physician interactions in the neurological setting (e.g., developing a therapeutic alliance; frame/boundary setting; active, empathic listening; acknowledging affect). These practices relate to a broad range of conditions, including, but not necessarily limited to epilepsy, traumatic brain injury, and functional neurological (conversion) disorder. The authors provide practical approaches that a neurologist can learn to leverage psychotherapeutic tools to enhance clinical encounters., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study was undertaken to determine whether undiagnosed illness duration (time between functional seizures [FS] onset and diagnosis) is linked to differences in neural response and functional connectivity during processing of stressful experiences., Methods: Forty-nine participants with traumatic brain injury preceding the onset of FS confirmed by video-electroencephalography were recruited prospectively. Participants completed psychiatric symptom assessments before undergoing functional magnetic resonance imaging (fMRI) with an acute psychosocial stress task. Linear mixed effects (LME) analyses identified significant interactions between the factors of group (early vs. delayed diagnosis) and time lag to diagnosis on neural responses to stressful math performance and auditory feedback (corrected α = .05). Functional connectivity analysis utilized clusters from initial LME analyses as seed regions to determine significant interactions between these factors on network functional connectivity., Results: Demographic and psychiatric symptom measures were similar between early (n = 25) and delayed (n = 24) groups. Responses to stressful math performance within the left anterior insula and functional connectivity between the anterior insula seed region and a precentral gyrus cluster were significantly negatively correlated with time lag to diagnosis for the early but not the delayed FS diagnosis group. There was no correlation between fMRI findings and psychiatric symptoms., Significance: This study indicates that aberrant left anterior insula activation and its functional connectivity to the precentral gyrus underlie differences in processing of stressful experiences in patients with delayed FS diagnosis. Follow-up comparisons suggest changes are associated with undiagnosed illness duration rather than psychiatric comorbidities and indicate a potential mechanistic association between neuropathophysiology, response to stressful experiences, and functional neuroanatomy in FS., (© 2022 International League Against Epilepsy.)

Functional seizures (FS) known also as psychogenic non-epileptic seizures or dissociative seizures, present with ictal semiological manifestations, along with various comorbid neurological and psychological disorders. Terminology inconsistencies and discrepancies in nomenclatures of FS may reflect limitations in understanding the neuropsychiatric intricacies of this disorder. Psychological and neurobiological processes of FS are incompletely understood. Nevertheless, important advances have been made on underlying neuropsychopathophysiological mechanisms of FS. These advances provide valuable information about the underlying mechanisms of mind-body interactions. From this perspective, this narrative review summarises recent studies about aetiopathogenesis of FS at two levels: possible risk factors (why) and different aetiopathogenic models of FS (how). We divided possible risk factors for FS into three categories, namely neurobiological, psychological and cognitive risk factors. We also presented different models of FS based on psychological and neuroanatomical understanding, multilevel models and integrative understanding of FS. This work should help professionals to better understand current views on the multifactorial mechanisms involved in the development of FS. Shedding light on the different FS profiles in terms of aetiopathogenesis will help guide how best to direct therapy, based on these different underlying mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Psychogenic nonepileptic seizures (PNES) are characterized by multifocal and global abnormalities in brain function and connectivity. Only a few studies have examined neuroanatomic correlates of PNES. Traumatic brain injury (TBI) is reported in 83% of patients with PNES and may be a key component of PNES pathophysiology. In this study, we included patients with TBI preceding the onset of PNES (TBI-PNES) and TBI without PNES (TBI-only) to identify neuromorphometric abnormalities associated with PNES., Methods: Adults diagnosed with TBI-PNES (n = 62) or TBI-only (n = 59) completed psychological questionnaires and underwent 3-T magnetic resonance imaging. Imaging data were analyzed by voxel- and surface-based morphometry. Voxelwise general linear models computed group differences in gray matter volume, cortical thickness, sulcal depth, fractal dimension (FDf), and gyrification. Statistical models were assessed with permutation-based testing at 5000 iterations with the Threshold-Free Cluster Enhancement toolbox. Logarithmically scaled p-values corrected for multiple comparisons using familywise error were considered significant at p < .05. Post hoc analyses determined the association between structural and psychological measures (p < .05)., Results: TBI-PNES participants demonstrated atrophy of the left inferior frontal gyrus and the right cerebellum VIII. Relative to TBI-only, TBI-PNES participants had decreased FDf in the right superior parietal gyrus and decreased sulcal depth in the left insular cortex. Significant clusters were positively correlated with global assessment of functioning scores, and demonstrated varying negative associations with measures of anxiety, depression, somatization, and global severity of symptoms., Significance: The diagnosis of PNES was associated with brain atrophy and reduced cortical folding in regions implicated in emotion processing, regulation, and response inhibition. Cortical folds primarily develop during the third trimester of pregnancy and remain relatively constant throughout the remainder of one's life. Thus, the observed aberrations in FDf and sulcal depth could originate early in development. The convergence of environmental, developmental, and neurobiological factors may coalesce to reflect the neuropathophysiological substrate of PNES., (© 2021 International League Against Epilepsy.)

We report a survey of neurology residency program directors (PDs) and recent neurology residency graduates about the education provided during residency on functional seizures (FS), a subtype of functional neurological disorder (FND). The purpose of our study was to assess the education gap for neurology residents about FS since patients with FS are frequently seen by neurologists, who typically conduct the evaluation and share the findings with the patient. A survey was sent to 93 Neurology residency program directors and 71 recent graduates. We obtained a low response rate of 17%. Results of the survey revealed that the most frequent settings for education on FS were within a clinical rotation in the Epilepsy Monitoring Unit (68.8% of PDs and 88.7% of recent graduate respondents) and via a single didactic lecture (81.3% of PDs and 80.3% of recent graduate respondents). The majority of programs did not provide a curriculum for training and feedback on best practices in communicating the diagnosis or on evidence-based treatments. Eighteen percent of neurology residents reported not learning how to communicate the diagnosis of FS to patients, while 77% responded that they were not taught about treatment. These results illustrate a curriculum gap in what neurology residents are taught about diagnosis and management of FS (and FND). We propose a standardized model that can be adapted in residencies., Competing Interests: Dr. Dworetzky, Baslet, and LaFrance receive authors’ royalties from Oxford University Press. The other authors report no disclosures., (© 2021 The Authors.)

Clinical interest in using psychological interventions for people with epilepsy (PWE) aiming at decreasing mental health difficulties, improving health-related quality of life (HRQOL) and seizure-related outcomes, continues to grow. This article summarizes the 2020 update of the 2017 Cochrane Review and meta-analysis of psychological interventions for PWE, highlighting the reasons for major methodological modifications such as the recategorization of interventions and expanded risk of bias assessment. A 2020 literature search yielded 36 RCTs (n=3526) investigating psychological treatments for PWE with a validated HRQOL measure as an outcome. Twenty-seven trials were skills-based psychological interventions, whilst nine studies were education-only interventions. Among skills-based psychological interventions, 11 studies (n=643) used the Quality of Life in Epilepsy-31 (QOLIE-31) or other QOLIE inventories convertible to QOLIE-31 as an outcome measure and were pooled for meta-analysis. Significant mean changes were observed for the QOLIE-31 total score (mean improvement of 5.23 points; p< 0.001) and in six out of seven subscales (emotional well-being, energy and fatigue, overall QoL, seizure worry, medication and cognitive functioning). The mean changes in the QOLIE-31 total score and the overall QoL subscale exceeded the threshold of minimally important change (MIC), indicating clinically meaningful post-intervention improvement. These results provide moderate evidence that psychological treatments for adults and adolescents with epilepsy enhance HRQOL. In addition to the summary of the Cochrane review, we provide a detailed characterization of the interventions and patient populations of the meta-analyzed studies.

Amongst the most important conditions in the differential diagnosis of epilepsy is the one that manifests as paroxysms of altered behaviour, awareness, sensation or sense of bodily control in ways that often resemble epileptic seizures, but without the abnormal excessive or synchronous electrical activity in the brain that defines these. Despite this importance, there remains little agreement - and frequent debate - on what to call this condition, known inter alia as psychogenic non-epileptic seizures (PNES), dissociative seizures (DS), functional seizures (FS), non-epileptic attack disorder (NEAD), pseudoseizures, conversion disorder with seizures, and by many other labels besides. This choice of terminology is not merely academic - it affects patients' response to and understanding of their diagnosis, and their ability to navigate health care systems.This paper summarises two recent discussions hosted by the American Epilepsy Society and Functional Neurological Disorders Society on the naming of this condition. These discussions are conceptualised as the initial step of an exploration of whether it might be possible to build consensus for a new diagnostic label., (Copyright © 2021 British Epilepsy Association. All rights reserved.)

The American Neuropsychiatric Association's Committee on Research assigned the task of defining the most helpful clinical factors and tests in establishing the diagnosis of psychogenic nonepileptic seizures (PNES) during a neuropsychiatric assessment. A systematic review of the literature was conducted using three search engines and specified search terms for PNES and the predetermined clinical factors and diagnostic tests, followed by a selection process with specific criteria. Data extraction results from selected articles are presented for clinical factors (semiology, psychiatric comorbidities, medical comorbidities, psychological traits) and diagnostic tests (EEG, psychometric and neuropsychological measures, prolactin level, clinical neuroimaging, autonomic testing). Semiology with video EEG (vEEG) remains the most valuable tool to determine the diagnosis of PNES. With the exception of semiology, very few studies revealed the predictive value of a clinical factor for PNES, and such findings were isolated and not replicated in most cases. Induction techniques, especially when coupled with vEEG, can lead to a captured event, which then confirms the diagnosis. In the absence of a captured event, postevent prolactin level and personality assessment can support the diagnosis but need to be carefully contextualized with other clinical factors. A comprehensive clinical assessment in patients with suspected PNES can identify several clinical factors and may include a number of tests that can support the diagnosis of PNES. This is especially relevant when the gold standard of a captured event with typical semiology on vEEG cannot be obtained.

Functional neurological (conversion) disorder (FND) is a prevalent and disabling condition at the intersection of neurology and psychiatry. Advances have been made in elucidating an emerging pathophysiology for motor FND, as well as in identifying evidenced-based physiotherapy and psychotherapy treatments. Despite these gains, important elements of the initial neuropsychiatric assessment of functional movement disorders (FND-movt) and functional limb weakness/paresis (FND-par) have yet to be established. This is an important gap from both diagnostic and treatment planning perspectives. In this article, the authors performed a narrative review to characterize clinically relevant variables across FND-movt and FND-par cohorts, including time course and symptom evolution, precipitating factors, medical and family histories, psychiatric comorbidities, psychosocial factors, physical examination signs, and adjunctive diagnostic tests. Thereafter, the authors propose a preliminary set of clinical content that should be assessed during early-phase patient encounters, in addition to identifying physical signs informing diagnosis and potential use of adjunctive tests for challenging cases. Although clinical history should not be used to make a FND diagnosis, characteristics such as acute onset, precipitating events (e.g., injury and surgery), and a waxing and waning course (including spontaneous remissions) are commonly reported. Active psychiatric symptoms (e.g., depression and anxiety) and ongoing psychosocial stressors also warrant evaluation. Positive physical examination signs (e.g., Hoover's sign and tremor entrainment) are key findings, as one of the DSM-5 diagnostic criteria. The neuropsychiatric assessment proposed emphasizes diagnosing FND by using "rule-in" physical signs while also considering psychiatric and psychosocial factors to aid in the development of a patient-centered treatment plan.

Evidence-based clinical practice guidelines, based on systematic reviews of existing evidence, play an important role in improving and standardizing the quality of patient care in many medical and psychiatric disorders, and could play an important role in the diagnosis and treatment of functional seizures and other functional neurological disorder (FND) subtypes. There are several reasons to think that evidence-based guidelines might be especially beneficial for the management of FND. In particular, the interdisciplinary and multidisciplinary teamwork necessary for the care of people with FND, the current lack of formal clinical training in FND, and the rapidly expanding body of evidence relating to FND all make guidelines based on systematic literature reviews especially valuable. In this perspective piece, we review clinical practice guidelines, their advantages and limitations, the reasons why evidence-based guidelines might be especially beneficial in the diagnosis and treatment of FND, and the steps that must be taken to create such guidelines for FND. We propose that professional organizations such as the American Academy of Neurology and the American Psychiatric Association undertake guideline development, ideally to create a co-authored or jointly endorsed set of guidelines that can set standards for interdisciplinary care for neurologists and mental health clinicians alike.

Background: Using machine learning to combine wrist accelerometer (ACM) and electrodermal activity (EDA) has been shown effective to detect primarily and secondarily generalized tonic-clonic seizures, here termed as convulsive seizures (CS). A prospective study was conducted for the FDA clearance of an ACM and EDA-based CS-detection device based on a predefined machine learning algorithm. Here we present its performance on pediatric and adult patients in epilepsy monitoring units (EMUs). Methods: Patients diagnosed with epilepsy participated in a prospective multi-center clinical study. Three board-certified neurologists independently labeled CS from video-EEG. The Detection Algorithm was evaluated in terms of Sensitivity and false alarm rate per 24 h-worn (FAR) on all the data and on only periods of rest. Performance were analyzed also applying the Detection Algorithm offline, with a less sensitive but more specific parameters configuration ("Active mode"). Results: Data from 152 patients (429 days) were used for performance evaluation (85 pediatric aged 6-20 years, and 67 adult aged 21-63 years). Thirty-six patients (18 pediatric) experienced a total of 66 CS (35 pediatric). The Sensitivity (corrected for clustered data) was 0.92, with a 95% confidence interval (CI) of [0.85-1.00] for the pediatric population, not significantly different ( p > 0.05) from the adult population's Sensitivity (0.94, CI: [0.89-1.00]). The FAR on the pediatric population was 1.26 (CI: [0.87-1.73]), higher ( p < 0.001) than in the adult population (0.57, CI: [0.36-0.81]). Using the Active mode, the FAR decreased by 68% while reducing Sensitivity to 0.95 across the population. During rest periods, the FAR's were 0 for all patients, lower than during activity periods ( p < 0.001). Conclusions: Performance complies with FDA's requirements of a lower bound of CI for Sensitivity higher than 0.7 and of a FAR lower than 2, for both age groups. The pediatric FAR was higher than the adult FAR, likely due to higher pediatric activity. The high Sensitivity and precision (having no false alarms) during sleep might help mitigate SUDEP risk by summoning caregiver intervention. The Active mode may be advantageous for some patients, reducing the impact of the FAR on daily life. Future work will examine the performance and usability outside of EMUs., Competing Interests: FO, GR, and CC are shareholders of Empatica Inc., which manufactured two of the devices used in this work and developed the two new algorithms tested in this work. GR is also an employee of Empatica and RP is also a consultant and chairs the board of directors for Empatica. TL is part of pending patent applications to detect and predict seizures and to diagnose epilepsy with devices different from the ones used in this work and has received research support from Empatica to conduct this research. TL, WL, and AB have received sensors from Empatica to perform the reported research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Onorati, Regalia, Caborni, LaFrance, Blum, Bidwell, De Liso, El Atrache, Loddenkemper, Mohammadpour-Touserkani, Sarkis, Friedman, Jeschke and Picard.)

Functional neurological disorder (FND) is a prevalent, disabling and costly condition at the neurology-psychiatry intersection. After being marginalised in the late 20th century, there has been renewed interest in this field. In this article, we review advances that have occurred over the past decade (2011-2020) across diagnosis, mechanisms, aetiologies, treatments and stigma in patients with motor FND (mFND, that is, functional movement disorder and functional limb weakness). In each content area, we also discuss the implications of recent advances and suggest future directions that will help continue the momentum of the past decade. In diagnosis, a major advance has been the emphasis on rule-in physical signs that are specific for hyperkinetic and hypokinetic functional motor symptoms. Mechanistically, greater importance has been given to determining 'how' functional neurological symptoms develop, highlighting roles for misdirected attention, expectation and self-agency, as well as abnormal influences of emotion/threat processing brain areas on motor control circuits. Aetiologically, while roles for adverse life experiences remain of interest in mFND, there is recognition of other aetiologic contributors, and efforts are needed to investigate links between aetiological factors and mechanisms. This decade has seen the first randomised controlled trials for physiotherapy, multidisciplinary rehabilitation and psychotherapy performed in the field, with consensus recommendations for physiotherapy, occupational therapy and outcome measures also published. Across patients, clinicians, healthcare systems and society, stigma remains a major concern. While challenges persist, a patient-centred integrated clinical neuroscience approach is primed to carry forward the momentum of the past decade into the future., Competing Interests: Competing interests: DLP has received honoraria for continuing medical education lectures in functional neurological disorder and is on the editorial board of Epilepsy & Behavior. MH is an inventor of patents held by National Institutes of Health (NIH) for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulation; in relation to the latter, he has received license fee payments from the NIH (from Brainsway). He is on the medical advisory boards of Cala Health and Brainsway. He has research grants from Allergan for studies of methods to inject botulinum toxins, Medtronic, Inc. for a study of deep brain stimulation (DBS) for dystonia and Cala Health for studies of a device to suppress tremor. WCL receives editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures, 3rd edition (Cambridge University Press, 2010) and 4th edition (2018) and author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015) and receives research support from the Department of Defense (DoD W81XWH-17-0169)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The Psychology Task Force of the Medical Therapies Commission of the International League Against Epilepsy (ILAE) has been charged with taking steps to improve global mental health care for people with epilepsy. This study aimed to inform the direction and priorities of the Task Force by examining epilepsy healthcare providers' current practical experiences, barriers, and unmet needs around addressing depression and anxiety in their patients., Methods: A voluntary 27-item online survey was distributed via ILAE chapters and networks. It assessed practices in the areas of screening, referral, management, and psychological care for depression and anxiety. A total of 445 participants, from 67 countries (68% high income), commenced the survey, with 87% completing all components. Most respondents (80%) were either neurologists or epileptologists., Results: Less than half of respondents felt adequately resourced to manage depression and anxiety. There was a lack of consensus about which health professionals were responsible for screening and management of these comorbidities. About a third only assessed for depression and anxiety following spontaneous report and lack of time was a common barrier (>50%). Routine referrals to psychiatrists (>55%) and psychologists (>41%) were common, but approximately one third relied on watchful waiting. A lack of both trained mental health specialists (>55%) and standardized procedures (>38%) was common barriers to referral practices. The majority (>75%) of respondents' patients identified with depression or anxiety had previously accessed psychotropic medications or psychological treatments. However, multiple barriers to psychological treatments were endorsed, including accessibility difficulties (52%)., Significance: The findings suggest that while the importance of managing depression and anxiety in patients with epilepsy is being recognized, there are ongoing barriers to effective mental health care. Key future directions include the need for updated protocols in this area and the integration of mental health professionals within epilepsy settings., Competing Interests: Author Gandy, Modi, Wagner, LaFrance, Reuber, Tang, Valente, Donald, and Michaelis received a travel stipend from the ILAE to attend the 33rd International Epilepsy Congress in Bangkok Thailand (June 2019), during which the Task Force had one‐day meeting where the promotion and results of the survey were discussed. Author Gandy is supported by a Macquarie University Research Fellowship. She develops and evaluates psychological treatment programs for adults with neurological disorders, including epilepsy. These clinical trials follow CONSORT reporting standards and are ethics committee‐approved and peer‐reviewed to address any potential bias. Author Modi receives research funding from the National Institutes of Health for clinical trials related to psychological treatments for youth with epilepsy. These clinical trials follow CONSORT reporting standards and are ethics committee‐approved and peer‐reviewed to address any potential bias. Author Wagner receives research funding from the National Institutes of Health for clinical trials related to psychological treatments for youth with epilepsy. These clinical trials follow CONSORT reporting standards and are ethics committee‐approved and peer‐reviewed to address any potential bias. Author LaFrance receives author royalties for the seizure treatment book Taking Control of Your Seizures: Workbook, Oxford University Press, 2015. He studies evidence‐based nonpharmacological interventions for people with seizures and receives funding from the US Congressionally Directed Medical Research Programs (CDMRP) (Award Number W81XWH‐17‐1‐0619) that are ethics committee‐approved and peer‐reviewed to address any potential bias. Author Reuber is responsible for developing and supervising a team of psychotherapists working in a clinical neurology department and provides treatment to people with epilepsy. He therefore has an interest in demonstrating the effectiveness of psychotherapy. However, this potential bias is outweighed by his interest in the development of evidence‐based treatments, encouraging him to assess the existing evidence as objectively and impartially as possible. Author Tang works as a clinical psychologist in a public hospital in Hong Kong under the Hospital Authority (“HA”). The views expressed are those of the author, and not necessarily those of the HA. She has received honoraria for speaking, and educational activities not funded by industry. She has no conflicts of interest to report. Author Valente receives personal grant from the National Council for Scientific and Technological Development (307817/2019‐9) and is responsible for four projects with grants from The Sao Paulo Research Foundation (2019/04956‐8; 2018/23798‐1; 2018/03228‐6; 2017/09870‐9). Author Donald works in a clinical environment where she sees and manages children with epilepsy, developmental, and intellectual disabilities and challenging behavior. She has received funding for unrelated research projects supported by the South African National Research Foundation and Medical Research Council, by an Academy of Medical Sciences Newton Advanced Fellowship (NAF002\1001), funded by the UK Government’s Newton Fund, by the National Institutes of Health (NIAAA, NIMH); UK MRC (MR/T002816/1) and by the US Brain and Behaviour Foundation Independent Investigator grant (24467). She has no conflicts of interest. Author Goldstein has received honoraria for speaking, and educational activities not funded by industry; she receives royalties from the publication of Clinical Neuropsychology (Wiley, 2004, 2013) and The Clinical Psychologist's Handbook of Epilepsy Cull 1997. This work represents independent research part‐funded by the NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, Psychology and Neuroscience, King’s College London. The views expressed are those of the author, and not necessarily those of the NHS, the NIHR or the Department of Health., (© 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using "rule-in" examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To utilize traumatic brain injury (TBI) as a model for investigating functioning during acute stress experiences in psychogenic nonepileptic seizures (PNES) and to identify neural mechanisms underlying the link between changes in processing of stressful experiences and mental health symptoms in PNES., Methods: We recruited 94 participants: 50 with TBI only (TBI-only) and 44 with TBI and PNES (TBI + PNES). Participants completed mood (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), and posttraumatic stress disorder (PTSD) symptom (PTSD Checklist-Specific Event) assessments before undergoing functional magnetic resonance imaging during an acute psychosocial stress task. Linear mixed-effects analyses identified clusters of significant interactions between group and neural responses to stressful math performance and stressful auditory feedback conditions within limbic brain regions (volume-corrected α = .05). Spearman rank correlation tests compared mean cluster signals to symptom assessments (false discovery rate-corrected α = .05)., Results: Demographic and TBI-related measures were similar between groups; TBI + PNES demonstrated worse clinical symptom severity compared to TBI-only. Stressful math performance induced relatively greater reactivity within dorsomedial prefrontal cortex (PFC) and right hippocampal regions and relatively reduced reactivity within left hippocampal and dorsolateral PFC regions for TBI + PNES compared to TBI-only. Stressful auditory feedback induced relatively reduced reactivity within ventral PFC, cingulate, hippocampal, and amygdala regions for TBI + PNES compared to TBI-only. Changes in responses to stressful math within hippocampal and dorsal PFC regions were correlated with increased mood, anxiety, and PTSD symptom severity., Significance: Corticolimbic functions underlying processing of stressful experiences differ between patients with TBI + PNES and those with TBI-only. Relationships between these neural responses and symptom assessments suggest potential pathophysiologic mechanisms in PNES., (© 2020 International League Against Epilepsy.)

A dualistic mind-body understanding of functional neurological disorders (FNDs), also known as conversion disorders, has led to the view that the cause of the symptom should be either psychological (psychogenic) or physical (neurogenic-"organic"). One of the most influential psychological approaches is the Freudian model of conversion, which suggests that FNDs arise from a defense process in which emotional stress is converted into physical symptoms. This conversion theory has been challenged in recent years, accompanied by a shift in emphasis toward neuropathophysiological models of FND and away from historical psychological concepts. In this review, the authors consider the contemporary relevance of the conversion model from the neuroscientific perspective to reconcile the role of both psychological and biological factors in FND. A narrative review of recent neuroscientific findings pertaining to the conversion model of FND, encompassing neuroimaging, cognitive psychology, biological markers, and epigenetic studies, was performed. Research on the role of psychological stressors is discussed. Neurobiological mechanisms of repression of traumatic memories and their translation into physical symptoms are then explored. Finally, the role of physical symptoms as a potential protective defense mechanism against social stressors is considered. The authors argue that the conversion concept is consistent with recent neuroscientific research findings, and the model allows psychological and neurobiological concepts to be reconciled within a single account of FND that begins to resolve the dualistic mind-body dichotomy.