Reduced Subjective Cognitive Concerns With Neurobehavioral Therapy in Functional Seizures and Traumatic Brain Injury.

OBJECTIVE: Functional seizures are common among people with traumatic brain injury (TBI). Subjective cognitive concerns refer to a person's own perception of problems with cognitive functioning in everyday life. The authors investigated the presence and correlates of subjective cognitive concerns and the response to neurobehavioral therapy among adults with TBI and functional seizures (TBI+FS group). METHODS: In this observational study, participants in the TBI+FS group (N=47) completed a 12-session neurobehavioral therapy protocol for seizures, while participants in the comparison group (TBI without seizures) (N=50) received usual treatment. Subjective cognitive concerns, objective cognition, mental health, and quality of life were assessed before and after treatment. Data collection occurred from 2018 to 2022. RESULTS: Baseline subjective cognitive concerns were reported for 37 (79%) participants in the TBI+FS group and 20 (40%) participants in the comparison group. In a multivariable regression model in the TBI+FS group, baseline global mental health (ß=-0.97) and obsessive-compulsive symptoms (ß=-1.01) were associated with subjective cognitive concerns at baseline. The TBI+FS group had fewer subjective cognitive concerns after treatment (η2=0.09), whereas the TBI comparison group showed a nonsignificant increase in subjective cognitive concerns. CONCLUSIONS: Subjective cognitive concerns are common among people with TBI and functional seizures and may be related to general mental health and obsessive-compulsive symptoms. Evidence-based neurobehavioral therapy for functional seizures is a reasonable treatment option to address such concerns in this population, although additional studies in culturally diverse samples are needed. In addition, people with functional seizures would likely benefit from rehabilitation specifically targeted toward cognitive functioning.

Brain network entropy, depression, and quality of life in people with traumatic brain injury and seizure disorders.

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.

Decreased uncinate fasciculus integrity in functional seizures following traumatic brain injury.

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.

Role of Deployment History on the Association Between Epilepsy and Traumatic Brain Injury in Post-9/11 Era US Veterans.

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.

Improvements in Montreal Cognitive Assessment scores after neurobehavioral therapy in adults with functional (nonepileptic) seizures and traumatic brain injury.

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.

Integrated psychological care services within seizure settings: Key components and implementation factors among example services in four ILAE regions: A report by the ILAE Psychiatry Commission.

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.

White Matter Changes after Neurobehavioral Therapy for Functional Seizures.

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.

Clinician-rated outcomes of patients with functional neurological disorders treated in an outpatient clinic.

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.

Relationship between intrinsic network connectivity and psychiatric symptom severity in functional seizures.

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.

Treatment of Psychogenic Nonepileptic Seizures.

PURPOSE OF REVIEW: Psychogenic nonepileptic seizures (PNES) are the most common Functional Neurological Disorder/Conversion Disorder subtype. Significant advances have been made related to diagnosis, neurobiology, and treatment. In this review, we summarize updates in diagnosis and management over the past 3 years. RECENT FINDINGS: Although evidence is mixed for the treatment of PNES, psychotherapeutic modalities remain a powerful instrument to empower patients and reduce seizures. A multidisciplinary, holistic approach is beneficial. While seizure freedom in all patients may not be the achieved endpoint in this chronic, paroxysmal disorder, quality of life can be improved with treatment. Additional treatment modalities and further research are needed for patients who are refractory to current treatment. Evidence-based therapies exist for PNES, and recent findings represent an increased understanding of the clinical and neurophysiologic aspects of PNES.

Reduction of the Adult Epilepsy Self-Management Measure Instrument (AESMMI).

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.

Diagnostic delay in functional seizures is associated with abnormal processing of facial emotions.

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.

Psychotherapeutic Tools to Enhance the Neurologist-Patient Interaction.

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.

Precentral gyrus and insula responses to stress vary with duration to diagnosis in functional seizures.

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.

Regional brain atrophy and aberrant cortical folding relate to anxiety and depression in patients with traumatic brain injury and psychogenic nonepileptic seizures.

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.

Functional (psychogenic non-epileptic/dissociative) seizures: why and how?

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.

The role of evidence-based guidelines in the diagnosis and treatment of functional neurological disorder.

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.