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.

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.

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.

Outpatient Approach to Occupational Therapy for Paroxysmal Functional Neurologic Symptoms: Sensory Modulation Training as an Emerging Treatment.

Occupational therapy (OT) is an important treatment modality for patients with paroxysmal functional neurologic disorder (FND) symptoms. In our clinical experience, an outpatient, OT-based sensory modulation treatment can address sensory processing difficulties often endorsed by patients with paroxysmal motor FND and functional seizures. This article aims to describe in detail the goals and treatment strategies for occupational therapists to replicate this approach. This article is also an important first step in aiding the development and execution of clinical trials to further evaluate the effectiveness of sensory-based treatment in patients with FND.

Feasibility and Validity of the Coma Recovery Scale-Revised for Accelerated Standardized Testing: A Practical Assessment Tool for Detecting Consciousness in the Intensive Care Unit.

We developed and validated an abbreviated version of the Coma Recovery Scale-Revised (CRS-R), the CRS-R For Accelerated Standardized Testing (CRSR-FAST), to detect conscious awareness in patients with severe traumatic brain injury in the intensive care unit. In 45 consecutively enrolled patients, CRSR-FAST administration time was approximately one-third of the full-length CRS-R (mean [SD] 6.5 [3.3] vs 20.1 [7.2] minutes, p < 0.0001). Concurrent validity (simple kappa 0.68), test-retest (Mak's ρ = 0.76), and interrater (Mak's ρ = 0.91) reliability were substantial. Sensitivity, specificity, and accuracy for detecting consciousness were 81%, 89%, and 84%, respectively. The CRSR-FAST facilitates serial assessment of consciousness, which is essential for diagnostic and prognostic accuracy. ANN NEUROL 2023;94:919-924.

Sensitivity to Change and Responsiveness of the Upper Extremity Fugl-Meyer Assessment in Individuals With Moderate to Severe Acute Stroke.

BACKGROUND: The Fugl-Meyer Assessment-Upper Extremity (FMA-UE) is a widely used outcome measure for quantifying motor impairment in stroke recovery. Meaningful change (responsiveness) in the acute to subacute phase of stroke recovery has not been determined. OBJECTIVE: Determine responsiveness and sensitivity to change of the FMA-UE from 1-week to 6-weeks (subacute) after stroke in individuals with moderate to severe arm impairment who received standard clinical care. METHODS: A total of 51 participants with resulting moderate and severe UE hemiparesis after stroke had FMA-UE assessment at baseline (within 2 weeks of stroke) and 6-weeks later. Sensitivity to change was assessed using Glass's delta, standardized response means (SRM), standard error of measure (SEM), and minimal detectable change (MDC). Responsiveness was assessed with the minimal clinically important difference (MCID), estimated using receiver operating characteristic curve analysis with patient-reported global rating of change scales (GROC) and a provider-reported modified Rankin Scale (mRS) as anchors. RESULTS: The MCID estimates were 13, 12, and 9 anchored to the GROC Arm Weakness, GROC Recovery, and mRS. Glass's delta and the SRM revealed large effect sizes, indicating high sensitivity to change, (∆ = 1.24, 95% CI [0.64, 1.82], SRM = 1.10). Results for the SEM and MDC were 2.46 and 6.82, respectively. CONCLUSION: The estimated MCID for the FMA-UE for individuals with moderate to severe motor impairment from 1 to 6-weeks after stroke is 13. These estimates will provide clinical context for FMA-UE change scores by helping to identify the change in upper-extremity motor impairment that is both beyond measurement error and clinically meaningful.

Distinguishing Distinct Neural Systems for Proximal vs Distal Upper Extremity Motor Control After Acute Stroke.

BACKGROUND AND OBJECTIVES: The classic and singular pattern of distal greater than proximal upper extremity motor deficits after acute stroke does not account for the distinct structural and functional organization of circuits for proximal and distal motor control in the healthy CNS. We hypothesized that separate proximal and distal upper extremity clinical syndromes after acute stroke could be distinguished and that patterns of neuroanatomical injury leading to these 2 syndromes would reflect their distinct organization in the intact CNS. METHODS: Proximal and distal components of motor impairment (upper extremity Fugl-Meyer score) and strength (Shoulder Abduction Finger Extension score) were assessed in consecutively recruited patients within 7 days of acute stroke. Partial correlation analysis was used to assess the relationship between proximal and distal motor scores. Functional outcomes including the Box and Blocks Test (BBT), Barthel Index (BI), and modified Rankin scale (mRS) were examined in relation to proximal vs distal motor patterns of deficit. Voxel-based lesion-symptom mapping was used to identify regions of injury associated with proximal vs distal upper extremity motor deficits. RESULTS: A total of 141 consecutive patients (49% female) were assessed 4.0 ± 1.6 (mean ± SD) days after stroke onset. Separate proximal and distal upper extremity motor components were distinguishable after acute stroke (p = 0.002). A pattern of proximal more than distal injury (i.e., relatively preserved distal motor control) was not rare, observed in 23% of acute stroke patients. Patients with relatively preserved distal motor control, even after controlling for total extent of deficit, had better outcomes in the first week and at 90 days poststroke (BBT, ρ = 0.51, p < 0.001; BI, ρ = 0.41, p < 0.001; mRS, ρ = 0.38, p < 0.001). Deficits in proximal motor control were associated with widespread injury to subcortical white and gray matter, while deficits in distal motor control were associated with injury restricted to the posterior aspect of the precentral gyrus, consistent with the organization of proximal vs distal neural circuits in the healthy CNS. DISCUSSION: These results highlight that proximal and distal upper extremity motor systems can be selectively injured by acute stroke, with dissociable deficits and functional consequences. Our findings emphasize how disruption of distinct motor systems can contribute to separable components of poststroke upper extremity hemiparesis.

Sensory Processing Difficulties in Patients with Functional Neurological Disorder: Occupational Therapy Management Strategies and Two Cases.

Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry, with some patients experiencing sensory hypersensitivities and other sensory processing difficulties. It has been postulated that poor integration and modulation of sensory information with cognitive, affective and behavioral processes may play a role in the pathophysiology of FND. In this article, we first succinctly review the role for occupational therapy (OT) in the multidisciplinary therapeutic approach to managing patients with FND. After highlighting previously published data identifying sensory processing difficulties in patients with FND, we subsequently outline the components of the sensory-based outpatient OT program for FND at the Massachusetts General Hospital. Here, we detail how occupational therapists assess and treat sensory modulation difficulties with the aid of resources like the Adolescent/Adult Sensory Profile (AASP), The Canadian Occupational Performance Measure (COPM), and the Sensory-Motor Preference Checklist. We then report on 2 clinical cases representative of the sensory modulation difficulties endorsed by some patients with FND, illustrating how developing an individualized, sensory-based treatment plan can help improve functional neurological symptoms and overall participation in activities of daily living. Prospective, controlled research is needed to further operationalize OT-based sensory modulation interventions, as well as define the tolerability and efficacy of this intervention for pediatric and adult populations with FND.

Cognitive Demands Influence Upper Extremity Motor Performance During Recovery From Acute Stroke.

OBJECTIVE: To test the hypothesis that cognitive demands influence motor performance during recovery from acute stroke, we tested patients with acute stroke on 2 motor tasks with different cognitive demands and related task performance to cognitive impairment and neuroanatomic injury. METHODS: We assessed the contralesional and ipsilesional upper extremities of a cohort of 50 patients with weakness after unilateral acute ischemic stroke at 3 time points with 2 tasks: the Box & Blocks Test, a task with greater cognitive demand, and Grip Strength, a simple and ballistic motor task. We compared performance on the 2 tasks, related motor performance to cognitive dysfunction, and used voxel-based lesion symptom mapping to determine neuroanatomic sites associated with motor performance. RESULTS: Consistent across contralesional and ipsilesional upper extremities and most pronounced immediately after stroke, Box & Blocks scores were significantly more impaired than Grip Strength scores. The presence of cognitive dysfunction significantly explained up to 33% of variance in Box & Blocks performance but was not associated with Grip Strength performance. While Grip Strength performance was associated with injury largely restricted to sensorimotor regions, Box & Blocks performance was associated with broad injury outside sensorimotor structures, particularly the dorsal anterior insula, a region known to be important for complex cognitive function. CONCLUSIONS: Together, these results suggest that cognitive demands influence upper extremity motor performance during recovery from acute stroke. Our findings emphasize the integrated nature of motor and cognitive systems and suggest that it is critical to consider cognitive demands during motor testing and neurorehabilitation after stroke.

Arm Motor Recovery After Ischemic Stroke: A Focus on Clinically Distinct Trajectory Groups.

BACKGROUND AND PURPOSE: Recovery of arm function poststroke is highly variable with some people experiencing rapid recovery but many experiencing slower or limited functional improvement. Current stroke prediction models provide some guidance for clinicians regarding expected motor outcomes poststroke but do not address recovery rates, complicating discharge planning. This study developed a novel approach to defining recovery groups based on arm motor recovery trajectories poststroke. In addition, between-group differences in baseline characteristics and therapy hours were explored. METHODS: A retrospective cohort analysis was conducted where 40 participants with arm weakness were assessed 1 week, 6 weeks, 3 months, and 6 months after an ischemic stroke. Arm recovery trajectory groups were defined on the basis of timing of changes in the Fugl-Meyer Assessment Upper Extremity (FMA-UE), at least the minimal clinically important difference (MCID), 1 week to 6 weeks or 6 weeks to 6 months. Three recovery trajectory groups were defined: Fast (n = 19), Extended (n = 12), and Limited (n = 9). Between-group differences in baseline characteristics and therapy hours were assessed. Associations between baseline characteristics and group membership were also determined. RESULTS: Three baseline characteristics were associated with trajectory group membership: FMA-UE, NIH Stroke Scale, and Barthel Index. The Fast Recovery group received the least therapy hours 6 weeks to 6 months. No differences in therapy hours were observed between Extended and Limited Recovery groups at any time points. DISCUSSION AND CONCLUSIONS: Three clinically relevant recovery trajectory groups were defined using the FMA-UE MCID. Baseline impairment, overall stroke severity, and dependence in activities of daily living were associated with group membership and therapy hours differed between groups. Stratifying individuals by recovery trajectory early poststroke could offer additional guidance to clinicians in discharge planning.(See Supplemental Digital Content 1 for Video Abstract, available at: http://links.lww.com/JNPT/A337.).