Machine learning classification of functional neurological disorder using structural brain MRI features.

BACKGROUND: Brain imaging studies investigating grey matter in functional neurological disorder (FND) have used univariate approaches to report group-level differences compared with healthy controls (HCs). However, these findings have limited translatability because they do not differentiate patients from controls at the individual-level. METHODS: 183 participants were prospectively recruited across three groups: 61 patients with mixed FND (FND-mixed), 61 age-matched and sex-matched HCs and 61 age, sex, depression and anxiety-matched psychiatric controls (PCs). Radial basis function support vector machine classifiers with cross-validation were used to distinguish individuals with FND from HCs and PCs using 134 FreeSurfer-derived grey matter MRI features. RESULTS: Patients with FND-mixed were differentiated from HCs with an accuracy of 0.66 (p=0.005; area under the receiving operating characteristic (AUROC)=0.74); this sample was also distinguished from PCs with an accuracy of 0.60 (p=0.038; AUROC=0.56). When focusing on the functional motor disorder subtype (FND-motor, n=46), a classifier robustly differentiated these patients from HCs (accuracy=0.72; p=0.002; AUROC=0.80). FND-motor could not be distinguished from PCs, and the functional seizures subtype (n=23) could not be classified against either control group. Important regions contributing to statistically significant multivariate classifications included the cingulate gyrus, hippocampal subfields and amygdalar nuclei. Correctly versus incorrectly classified participants did not differ across a range of tested psychometric variables. CONCLUSIONS: These findings underscore the interconnection of brain structure and function in the pathophysiology of FND and demonstrate the feasibility of using structural MRI to classify the disorder. Out-of-sample replication and larger-scale classifier efforts incorporating psychiatric and neurological controls are needed.

Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

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.

Harnessing Placebo Effects for the Treatment of Functional Cognitive Disorder: A Feasibility Pilot Study.

OBJECTIVE: Limited research has directly investigated whether and how placebo effects can be harnessed for the treatment of functional neurological disorder (FND), despite a long-standing and controversial history of interest in this area. METHODS: A small exploratory study was conducted with adults with a cognitive subtype of FND recruited from a single cognitive neurology center in the United States. Participants were given the expectation of receiving cranial stimulation that could benefit their memory symptoms; however, the intervention was sham transcranial magnetic stimulation (placebo). Outcomes included measures of short-term memory testing, subjective memory rating, and state anxiety before and after stimulation. After the study, the true objective and rationale for investigating placebo effects were explained in a scripted debriefing session. Acceptability of the study design and qualitative feedback were collected. Institutional ethics approval and signed consent were obtained. RESULTS: Three patients (female, N=2; male, N=1; average age=57 years) were recruited. Outcome data were analyzed descriptively at the patient level. Trends of improvement in subjective memory rating, but not objective cognitive test scores, and decreases in state anxiety were observed. After the debriefing session, all patients found the study design to be acceptable (ratings of 70%, 90%, and 100%), and two of the three patients believed that withholding mechanistic information about the intervention was needed to leverage placebo effects as treatment. CONCLUSIONS: In the first study to prospectively investigate the feasibility of harnessing placebo effects for the treatment of FND, promising preliminary findings were obtained, and methods and resources for use in larger future studies are offered.

Telemedicine-Based Cognitive Examinations During COVID-19 and Beyond: Perspective of the Massachusetts General Hospital Behavioral Neurology & Neuropsychiatry Group.

Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

A new science of emotion: implications for functional neurological disorder.

Functional neurological disorder reflects impairments in brain networks leading to distressing motor, sensory and/or cognitive symptoms that demonstrate positive clinical signs on examination incongruent with other conditions. A central issue in historical and contemporary formulations of functional neurological disorder has been the mechanistic and aetiological role of emotions. However, the debate has mostly omitted fundamental questions about the nature of emotions in the first place. In this perspective article, we first outline a set of relevant working principles of the brain (e.g. allostasis, predictive processing, interoception and affect), followed by a focused review of the theory of constructed emotion to introduce a new understanding of what emotions are. Building on this theoretical framework, we formulate how altered emotion category construction can be an integral component of the pathophysiology of functional neurological disorder and related functional somatic symptoms. In doing so, we address several themes for the functional neurological disorder field including: (i) how energy regulation and the process of emotion category construction relate to symptom generation, including revisiting alexithymia, 'panic attack without panic', dissociation, insecure attachment and the influential role of life experiences; (ii) re-interpret select neurobiological research findings in functional neurological disorder cohorts through the lens of the theory of constructed emotion to illustrate its potential mechanistic relevance; and (iii) discuss therapeutic implications. While we continue to support that functional neurological disorder is mechanistically and aetiologically heterogenous, consideration of how the theory of constructed emotion relates to the generation and maintenance of functional neurological and functional somatic symptoms offers an integrated viewpoint that cuts across neurology, psychiatry, psychology and cognitive-affective neuroscience.

Lessons Learned in Outpatient Physical Therapy for Motor Functional Neurological Disorder.

BACKGROUND AND PURPOSE: Motor functional neurological disorder is a prevalent and costly condition at the intersection of neurology and psychiatry that is diagnosed using positive "rule-in" signs. Physical therapy is a first-line treatment and consensus recommendations exist to guide clinical care. Nonetheless, optimal outpatient treatment of adults with functional motor symptoms requires an expanded physical therapy tool kit to effectively guide care. SUMMARY OF KEY POINTS: In this article, lessons learned from a physical therapist practicing in a multidisciplinary and interdisciplinary outpatient functional neurological disorder clinic are highlighted. In doing so, we discuss how use of the biopsychosocial model and neuroscience constructs can inform physical therapy interventions. The importance of team-based care and the delivery of physical therapy through video telehealth services are also outlined. RECOMMENDATIONS FOR CLINICAL PRACTICE: Use of the biopsychosocial formulation to triage clinical challenges and guide longitudinal care, coupled with application of neuroscience to aid intervention selection, allows for patient-centered physical therapy treatment across the spectrum of functional motor symptoms.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A400 ).

Toward a Unified Classification System for Brain-Mind Disorders: Putting Calls for Integrated Clinical Neuroscience Into Action.

Dividing the brain-mind into the specialized fields of neurology and psychiatry has produced many granular advantages, but these silos have imposed barriers to comprehensively understanding and contextualizing the fundamentals governing mental life and its maladies. Scientific inquiry into these fundamentals cannot reach its full potential without interdigitating the boundaries of two specialties of the same organ for both scholarship and clinical practice. We propose that to truly integrate disorders of the brain and the mind for research and clinical care, we must carefully reexamine the classification of its disorders (nosology) as an instrument to develop a coherent pathological and psychological framework. We call on professional organizations from neurology, psychiatry, behavioral neurology, neuropsychiatry, neuropsychology, and other relevant subspecialties (eg, geriatric psychiatry) to convene a multidisciplinary task force to define the current classification principles of their subspecialties and work toward developing an integrated nosology. The effect of a shared classification system, which we acknowledge is a difficult proposition philosophically and politically, would have transformative potential across educational, clinical, scientific, programmatic, and sociocultural realms. If accomplished, this initiative would provide a definitive step toward reducing stigma (and promoting reimbursement parity) for the full spectrum of complex brain disorders (regardless of traditional neurologic vs psychiatric conceptualizations).

Neuromodulation for the treatment of functional neurological disorder and somatic symptom disorder: a systematic review.

Functional neurological disorder and somatic symptom disorder are complex neuropsychiatric conditions that have been linked to circuit-based dysfunction of brain networks. Neuromodulation is a novel therapeutic strategy capable of modulating relevant brain networks, making it a promising potential candidate for the treatment of these patient populations. We conducted a systematic review of Medline, Embase and PsycINFO up to 4 March 2021. Trials investigating neuromodulation devices for the treatment of functional neurological disorder or somatic symptom disorder were selected. Extracted variables included study design, demographic and clinical characteristics, psychiatric comorbidity, neurostimulation protocols, clinical outcome measures and results. 404 studies were identified with 12 meeting inclusion criteria. 221 patients were treated in the included studies with mean study sample size of 18 (4-70). Five studies were randomised clinical trials. Functional motor symptoms (six weakness, four movement disorders) were the most studied subpopulations. Transcranial magnetic stimulation (TMS) was the most frequently used device (10 studies), followed by electroconvulsive therapy (one study) and direct-current stimulation (one study). Treatment protocols varied in intended therapeutic mechanism(s): eight studies aimed to modulate underlying network dysfunction, five aimed to demonstrate movement (one also leveraged the former) and three boosted their primary mechanism with enhanced suggestion/expectation. All but one study reported positive results; however, methodological/outcome heterogeneity, mixed study quality and small sample sizes precluded quantitative meta-analysis. Neuromodulation, particularly TMS for the treatment of functional motor symptoms, shows preliminary promise in a growing line of research. Larger, sham-controlled studies are needed to further establish efficacy and better understand therapeutic mechanisms.

Early-life trauma endophenotypes and brain circuit-gene expression relationships in functional neurological (conversion) disorder.

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition whereby individuals present with sensorimotor symptoms incompatible with other neurological disorders. Early-life maltreatment (ELM) is a risk factor for developing FND, yet few studies have investigated brain network-trauma relationships in this population. In this neuroimaging-gene expression study, we used two graph theory approaches to elucidate ELM subtype effects on resting-state functional connectivity architecture in 30 patients with motor FND. Twenty-one individuals with comparable depression, anxiety, and ELM scores were used as psychiatric controls. Thereafter, we compared trauma endophenotypes in FND with regional differences in transcriptional gene expression as measured by the Allen Human Brain Atlas (AHBA). In FND patients only, we found that early-life physical abuse severity, and to a lesser extent physical neglect, correlated with corticolimbic weighted-degree functional connectivity. Connectivity profiles influenced by physical abuse occurred in limbic (amygdalar-hippocampal), paralimbic (cingulo-insular and ventromedial prefrontal), and cognitive control (ventrolateral prefrontal) areas, as well as in sensorimotor and visual cortices. These findings held adjusting for individual differences in depression/anxiety, PTSD, and motor phenotypes. In FND, physical abuse also correlated with amygdala and insula coupling to motor cortices. In exploratory analyses, physical abuse correlated connectivity maps overlapped with the AHBA spatial expression of three gene clusters: (i) neuronal morphogenesis and synaptic transmission genes in limbic/paralimbic areas; (ii) locomotory behavior and neuronal generation genes in left-lateralized structures; and (iii) nervous system development and cell motility genes in right-lateralized structures. These circuit-specific architectural profiles related to individual differences in childhood physical abuse burden advance our understanding of the pathophysiology of FND.

Using the Biopsychosocial Model to Guide Patient-Centered Neurological Treatments.

The biopsychosocial model was defined by George L. Engel to propose a holistic approach to patient care. Through this model, physicians can understand patients in their context to aid the development of tailored, individualized treatment plans that consider relevant biological, psychological, and social-cultural-spiritual factors impacting health and longitudinal care. In this article, we advocate for the use of the biopsychosocial model in neurology practice across outpatient and inpatient clinical settings. To do so, we first present the history of the biopsychosocial model, and its relationships to precision medicine and deep phenotyping. Then, we bring the neurologist up-to-date information on the components of the biopsychosocial clinical formulation, including predisposing, precipitating, perpetuating, and protective factors. We conclude by detailing illustrative neurological case examples using the biopsychosocial model, emphasizing the importance of considering relevant psychological and social factors to aid the delivery of patient-centered clinical care in neurology.

Neuropsychiatric Treatment Approaches for Functional Neurological Disorder: A How to Guide.

There is a growing body of knowledge regarding management of functional neurological disorder (FND). The aim of this article is to guide the clinician through FND clinical management, from delivery of the diagnosis, to creation of a biopsychosocially-informed treatment plan, to troubleshooting common issues that arise throughout longitudinal care. We review the evidence and core principles of both rehabilitative therapies (physical therapy, occupational therapy, and speech and language therapy) and psychological therapies for the treatment of FND, and discuss the benefits of engaging a multidisciplinary and interdisciplinary team. The optimal timing of specific therapeutic interventions is also discussed, emphasizing a patient-centered perspective. Resources for further reading, for both patients and clinicians, are provided throughout. Additional research is needed to further optimize the therapeutic approach to patients with FND, including the need to develop novel treatments for those that do not positively respond to currently available interventions.

Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: Functional neurological disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with FND, suggesting that gaps remain in our systems-level neurobiological understanding. As such, other important physiological variables, including autonomic, endocrine, and inflammation findings, need to be contextualized for a more complete mechanistic picture. METHODS: The investigators conducted a systematic review and meta-analysis of available case-control and cohort studies of FND. PubMed, PsycINFO, and Embase databases were searched for studies from January 1, 1900, to September 1, 2020, that investigated autonomic, endocrine, and inflammation markers in patients with FND. Sixty-six of 2,056 screened records were included in the review, representing 1,699 patients; data from 20 articles were used in the meta-analysis. RESULTS: Findings revealed that children and adolescents with FND, compared with healthy control subjects (HCs), have increased resting heart rate (HR); there is also a tendency toward reduced resting HR variability in patients with FND across the lifespan compared with HCs. In adults, peri-ictal HR differentiated patients with functional seizures from those with epileptic seizures. Other autonomic and endocrine profiles for patients with FND were heterogeneous, with several studies highlighting the importance of individual differences. CONCLUSIONS: Inflammation research in FND remains in its early stages. Moving forward, there is a need for the use of larger sample sizes to consider the complex interplay between functional neurological symptoms and behavioral, psychological, autonomic, endocrine, inflammation, neuroimaging, and epigenetic/genetic data. More research is also needed to determine whether FND is mechanistically (and etiologically) similar or distinct across phenotypes.

Cortical thickness in default mode network hubs correlates with clinical features of dissociative seizures.

BACKGROUND: Dissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated. METHODS: Forty-eight patients with DS without neurological comorbidities and 43 matched clinical control patients with syncope with structural brain MRIs were identified retrospectively. FreeSurfer-based cortical thickness and FSL FIRST-based subcortical volumes were used for quantitative analyses, and all findings were age and sex adjusted, and corrected for multiple comparisons. RESULTS: Groups were not statistically different in cortical thickness or subcortical volumes. For patients with DS, illness duration was inversely correlated with cortical thickness of left-sided anterior and posterior cortical midline structures (perigenual/dorsal anterior cingulate cortex, superior parietal cortex, precuneus), and clusters at the left temporoparietal junction (supramarginal gyrus, postcentral gyrus, superior temporal gyrus), left postcentral gyrus, and right pericalcarine cortex. Dissociative seizure duration was inversely correlated with cortical thickness in the left perigenual anterior cingulate cortex, superior/middle frontal gyri, precentral gyrus and lateral occipital cortex, along with the right isthmus-cingulate and posterior-cingulate, middle temporal gyrus, and precuneus. Seizure frequency did not show any significant correlations. CONCLUSIONS: In patients with DS, illness duration inversely correlated with cortical thickness of left-sided default mode network cortical hubs, while seizure duration correlated with left frontopolar and right posteromedial areas, among others. Etiological factors contributing to neuroanatomical variations in areas related to self-referential processing in patients with DS require more research inquiry.

Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study.

In motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel-based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND-seiz; n = 21) or functional movement disorders (n = 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within-group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self-reported bodily awareness). Results were corrected for multiple comparisons, and all findings were adjusted for depression and trait anxiety. mFND and HCs did not show any between-group interoceptive accuracy or FA differences. However, the FND-seiz subgroup compared to HCs showed decreased integrity in right-lateralized tracts: extreme capsule/inferior fronto-occipital fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, and thalamic/striatum to occipital cortex projections. These alterations originated predominantly from the right temporoparietal junction and inferior temporal gyrus. In mFND patients, individual differences in interoceptive accuracy and interoceptive trait prediction error correlated with fiber bundle integrity originating from the insula, temporoparietal junction, putamen and thalamus among other regions. In this first study investigating brain-interoception relationships in mFND, individual differences in interoceptive accuracy and trait prediction error mapped onto multimodal integration-related fiber bundles. Right-lateralized limbic and associative tract disruptions distinguished FND-seiz from HCs.

Decade of progress in motor functional neurological disorder: continuing the momentum.

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.

Reduced limbic microstructural integrity in functional neurological disorder.

BACKGROUND: Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration. METHODS: A diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons. RESULTS: Compared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients. CONCLUSIONS: In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.

Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures: A Report From the American Neuropsychiatric Association Committee on Research.

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.