Mechanistic studies in pathological health anxiety: A systematic review and emerging conceptual framework.

BACKGROUND: Pathological health anxiety (PHA) (e.g., hypochondriasis and illness anxiety disorder) is common in medical settings and associated with increased healthcare costs. However, the psychological and neurobiological mechanisms contributing to the development and maintenance of PHA are incompletely understood. METHODS: We performed a systematic review to characterize the mechanistic understanding of PHA. PubMed, PsycINFO, and Embase databases were searched to find articles published between 1/1/1990 and 12/31/2022 employing a behavioral task and/or physiological measures in individuals with hypochondriasis, illness anxiety disorder, and PHA more broadly. RESULTS: Out of 9141 records identified, fifty-seven met inclusion criteria. Article quality varied substantially across studies, and was overall inadequate. Cognitive, behavioral, and affective findings implicated in PHA included health-related attentional and memory recall biases, a narrow health concept, threat confirming thought patterns, use of safety-seeking behaviors, and biased explicit and implicit affective processing of health-related information among other observations. There is initial evidence supporting a potential overestimation of interoceptive stimuli in those with PHA. Neuroendocrine, electrophysiology, and brain imaging research in PHA are particularly in their early stages. LIMITATIONS: Included articles evaluated PHA categorically, suggesting that sub-threshold and dimensional health anxiety considerations are not contextualized. CONCLUSIONS: Within an integrated cognitive-behavioral-affective and predictive processing formulation, we theorize that sub-optimal illness and health concepts, altered interoceptive modeling, biased illness-based predictions and attention, and aberrant prediction error learning are mechanisms relevant to PHA requiring more research. Comprehensively investigating the pathophysiology of PHA offers the potential to identify adjunctive diagnostic biomarkers and catalyze new biologically-informed treatments.

Predictive Processing and the Pathophysiology of Functional Neurological Disorder.

The contemporary neuroscience understanding of the brain as an active inference organ supports that our conscious experiences, including sensorimotor perceptions, depend on the integration of probabilistic predictions with incoming sensory input across hierarchically organized levels. As in other systems, these complex processes are prone to error under certain circumstances, which may lead to alterations in their outcomes (i.e., variations in sensations and movements). Such variations are an important aspect of functional neurological disorder, a complex disorder at the interface of brain-mind-body interactions. Thus, predictive processing frameworks offer fundamental mechanistic insights into the pathophysiology of functional neurological disorder. In recent years, many of the aspects relevant to the neurobiology of functional neurological disorder - e.g., aberrant motor and sensory processes, symptom expectation, self-agency, and illness beliefs, as well as interoception, allostasis, and emotion - have been investigated through the lens of predictive processing frameworks. Here, we provide an overview of the current state of research on predictive processing and the pathophysiology of functional neurological disorder.

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.

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.

Sensory Processing Difficulties and Occupational Therapy Outcomes for Functional Neurological Disorder: A Retrospective Cohort Study.

Background and Objectives: Occupational therapy (OT) consensus recommendations and articles outlining a sensory-based OT intervention for functional neurological disorder (FND) have been published. However, limited research has been conducted to examine the efficacy of OT interventions for FND. We performed a retrospective cohort study aimed at independently replicating preliminarily characterized sensory processing difficulties in patients with FND and reporting on clinical outcomes of a sensory-based OT treatment in this population. We hypothesized that (1) a history of functional seizures, anxiety, and/or post-traumatic stress disorder would be associated with increased sensory processing difficulties and (2) the number of OT treatment sessions received would positively relate to clinical improvement. Methods: Medical records were reviewed for 77 consecutive adults with FND who received outpatient, sensory-based OT care. Data from the Adolescent/Adult Sensory Profile characterized self-reported sensory processing patterns across 4 quadrants (low registration, sensory sensitivity, sensory seeking, and sensory avoidance) in this population. Following univariate screenings, multivariate linear regression analyses were performed to identify neuropsychiatric characteristics associated with discrete sensory processing patterns. Clinical improvement was quantified using an estimated, clinician-determined improvement rating ("improved" vs "not improved"), and relationships between clinical participation, baseline neuropsychiatric factors, and outcomes were investigated. Results: Patients with FND reported sensory processing patterns with elevated scores in low registration, sensory sensitivity, and sensation avoidance compared with normative values; differences in sensory processing scores were not observed across FND subtypes (i.e., motor, seizure, and speech variants). In linear regression analyses, lifetime history of an anxiety disorder, history of migraine headaches, current cognitive complaints, and a comorbid major neurologic condition independently predicted individual differences in sensory processing scores. Following a sensory-based OT intervention, 62% of individuals with FND were clinician determined as "improved." In a multivariate logistic regression analysis controlling for baseline characteristics associated with improvement ratings, number of treatment sessions positively correlated with clinical improvement. Discussion: These findings support the presence of sensory processing difficulties in patients with FND and provide Class IV evidence for the efficacy of an outpatient, sensory-based OT intervention in this population. Controlled prospective trials are warranted.

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.

Inpatient Rehabilitation for Acute Presentations of Motor Functional Neurological Disorder: A Retrospective Cohort Study.

OBJECTIVE: Patients with functional neurological disorder involving the motor system (eg, functional weakness, functional gait) may acutely present to the hospital for new-onset symptoms. For some, symptoms may remain severe enough at the time of hospital discharge to qualify for an inpatient rehabilitation facility stay. DESIGN: Data were extracted via retrospective chart review on functional neurological disorder patients ( N = 22) admitted to an inpatient rehabilitation facility between September 2019 and May 2022. Demographic and clinical data, including admission and discharge physical and occupational therapy measurements on the Inpatient Rehabilitation Facility Patient Assessment Instrument, were recorded and analyzed. RESULTS: Symptom duration was less than 1 wk for nearly two thirds of the cohort. After an approximately 2-wk length of stay, patients showed statistically significant changes in admission to discharge measures of self-care, transfers, ambulation, and balance. More than 95% of patients were able to be discharged home. The presence or absence of comorbid depression, anxiety, or posttraumatic stress disorder did not impact outcomes. CONCLUSIONS: For a subset of patients with persistent motor symptoms after an acute hospital admission for a new diagnosis of functional neurological disorder, a relatively short inpatient rehabilitation facility stay was associated with significant clinical gains.

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.

Functional neurological disorder and functional somatic syndromes among sexual and gender minority people: A scoping review.

OBJECTIVE: To describe the current literature on functional neurological disorder and functional somatic syndromes among sexual and gender minority people (SGM). METHODS: A search string with descriptors of SGM identity and functional disorders was entered into PubMed, Embase, Web of Science, PsycInfo, and CINAHL for articles published before May 24, 2022, yielding 3121 items entered into Covidence, where 835 duplicates were removed. A neurologist and neuropsychiatrist screened titles and abstracts based on predefined criteria, followed by full-text review. A third neurologist adjudicated discrepancies. Eligible publications underwent systematic data extraction and statistical description. RESULTS: Our search identified 26 articles on functional disorders among SGM people. Most articles were case (13/26, 46%) or cross-sectional (4/26, 15%) studies. Gender minority people were represented in 50% of studies. Reported diagnoses included fibromyalgia (n = 8), functional neurological disorder (n = 8), somatic symptom disorder (n = 5), chronic fatigue syndrome (n = 3), irritable bowel syndrome (n = 2), and other functional conditions (n = 3). Three cohort studies of fibromyalgia or somatic symptom disorder reported an overrepresentation of gender minority people compared to cisgender cohorts or general population measures. Approximately half of case studies reported pediatric or adolescent onset (7/13, 54%), functional neurological disorder diagnosis (7/13, 54%), and symptom improvement coinciding with identity-affirming therapeutic interventions (7/13, 58%). CONCLUSION: Despite a methodologically rigorous literature search, there are limited data on functional neurological disorder and functional somatic syndromes among SGM people. Several studies reported increased prevalence of select conditions among transgender people. More observational studies are needed regarding the epidemiology and clinical course of functional disorders among SGM people.

The Impact of Depression, Anxiety and Personality Disorders on the Outcome of Patients with Functional Limb Weakness - Individual Patient Data Meta-Analysis.

OBJECTIVE: Psychiatric comorbidities such as depression, anxiety, and personality disorders are common in patients with functional limb weakness/paresis (FND-par). The impact of these conditions on the prognosis of FND-par has not been systematically reviewed. The aim of this study was to identify a potential prognostic effect of comorbid depression, anxiety, and/or personality disorder on prognosis in patients with FND-par. METHODS: A systematic review was performed to identify studies that reported measures of baseline depression, anxiety, and/or personality disorder, and physical disability. An individual patient data meta-analysis was subsequently performed. RESULTS: Eight studies comprising 348 individuals were included (7 prospective cohorts; 1 case-control study). There was heterogeneity in sample size, follow-up duration, and treatment modality. Depression and anxiety were present in 51.4% and 53.0% of FND-par patients, respectively. In individuals whose FND-par improved, there was no significant difference between those with versus without depression (52.6% vs 47.4%, p = 0.69) or those with versus without anxiety (50.3% vs 49.7%, p = 0.38). Meta-analysis showed no clear impact of baseline depression or anxiety per se [pooled OR for depression 0.85 (95%CI 0.50-1.45; p = 0.40) and anxiety 0.84 (95%CI 0.51-1.38; p = 0.91)]; and of depression or anxiety severity [pooled OR for depression 1.23 (95%CI 0.63-2.39; p = 0.91) and anxiety 1.40 (95%CI 0.70-2.78; p = 0.58)] on FND-par outcome. Insufficient data were available to assess the impact of personality disorders. CONCLUSION: We found no evidence that depression or anxiety influenced outcome in FND-par. Large-scale, prospective studies in FND-par, and other FND subtypes, are needed to fully contextualize the impact of concurrent mental health concerns on outcomes.

Toward a Precision Medicine Approach to the Outpatient Assessment and Treatment of Functional Neurological Disorder.

Functional neurological disorder (FND) is a neuropsychiatric condition. In this field, prospective psychotherapy trials and consensus recommendations for physiotherapy, occupational therapy, and speech language therapy have been published. However, significant clinical complexities remain. "Rule in" signs - while critical for making a positive diagnosis - do not equate to a personalized treatment plan in many instances. Here, we propose that the neuropsychiatric assessment and real-time development of a work-in-progress biopsychosocial clinical formulation aids the development of a patient-centered outpatient treatment plan. This precision medicine approach is based on the literature, expert opinions and our clinical experience working in an interdisciplinary FND service.

Developing a Curriculum for Functional Neurological Disorder in Neurology Training: Questions and Answers.

Functional neurologic disorder (FND) is a common condition for which neurology residents often receive little to no formal teaching. Using a question-and-answer format, this article puts forward a case for why an FND curriculum is needed and aims to provide guidance on possible curricular content including medical knowledge, clinical skills, communication, and team-based collaboration. The authors also discuss methods for teaching and evaluating this knowledge and associated clinical skills, linking this to current Accreditation Council for Graduate Medical Education neurology milestones. Finally, the authors consider how to better engage and energize neurology trainees around this underserved yet challenging patient population.

Setting up Functional Neurological Disorder Treatment Services: Questions and Answers.

Functional neurologic disorder (FND) is commonly encountered across outpatient and inpatient medical settings. Given the potential for a high burden of disability in some patients and mounting evidence for the efficacy of FND-specific multidisciplinary treatment services, expanding clinical services for this population is a necessity. In this perspective article, we discuss considerations for creating FND services, including the types of services that exist, how to start, how to identify appropriate referrals, and how to develop and monitor individualized treatment plans. In addition, we discuss how this effort can be done sustainably - balancing patient needs with limited healthcare resources.

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).