Minimal clinically important difference in the World Health Organization Quality of Life Brief (WHOQOL-BREF) for adults with neurofibromatosis.

PURPOSE: This study aimed to estimate minimal clinically important difference (MCID) values for the World Health Organization Quality of Life Brief version (WHOQOL-BREF) among adults with neurofibromatosis (NF). An MCID is needed to demonstrate clinical meaningfulness of interventions for NF. METHODS: We estimated MCID for the WHOQOL-BREF: the quality of life (QoL) measure recommended by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration. We used data from 228 clinical trial participants with NF type 1, NF type 2-related schwannomatosis, or schwannomatosis (SCHWN) who completed 10 weeks of a virtual group mind-body program targeting resiliency or a time- and attention-matched control. Following established guidelines, we estimated MCIDs using both anchor-based and distribution-based methods for physical, psychological, social relationships, and environmental domains of the WHOQOL-BREF. RESULTS: MCID results varied across method and QoL domain. Three anchor-based methods, average change (AC), change difference (CD), and regression (REG), yielded the most consistent and comparable MCID across QoL domains. Based on these methods, we recommend ranges for each QoL domain: Physical QoL (3.9-7.3), Psychological QoL (4.7-8.1), Social QoL (2.6-5.9), and Environmental QoL (4.1-6.6). CONCLUSION: Establishing a rigorous MCID for QoL in NF is a critical step toward evaluating meaningful change in response to psychosocial interventions.

Addressing the Chronic Pain-Early Cognitive Decline Comorbidity Among Older Adults: Protocol for the Active Brains Remote Efficacy Trial.

BACKGROUND: Chronic pain and early cognitive decline, which are costly to treat and highly prevalent among older adults, commonly co-occur, exacerbate one another over time, and can accelerate the development and progression of Alzheimer disease and related dementias. We developed the first mind-body activity program (Active Brains [AB]) tailored to the needs of older adults with chronic pain and early cognitive decline. Results from our previous study strongly supported the feasibility of conducting AB remotely and provided evidence for improvements in outcomes. OBJECTIVE: We are conducting a single-blinded, National Institutes of Health stage-2, randomized clinical trial to establish the efficacy of AB versus a time-matched and dose-matched education control (Health Enhancement Program [HEP]) in improving self-reported and objective outcomes of physical, cognitive, and emotional functions in 260 participants. The methodology described in this paper was informed by the lessons learned from the first year of the trial. METHODS: Participants are identified and recruited through multidisciplinary clinician-referred individuals (eg, pain psychologists and geriatricians), the Rally Research platform, social media, and community partnerships. Interested participants complete eligibility screening and electronic informed consent. Baseline assessments include self-report, performance-based measures (eg, 6-min walk test) and objective measures (eg, Repeatable Battery for the Assessment of Neuropsychological Status). Participants are mailed a wrist-worn ActiGraph device (ActiGraph LLC) to passively monitor objective function (eg, steps) during the week between the baseline assessment and the beginning of the programs, which they continue to wear throughout the programs. After baseline assessments, participants are randomized to either AB or HEP and complete 8 weekly, remote, group sessions with a Massachusetts General Hospital psychologist. The AB group receives a Fitbit (Fitbit Inc) to help reinforce increased activity. Assessments are repeated after the intervention and at the 6-month follow-up. Coprimary outcomes include multimodal physical function (self-report, performance based, and objective). Secondary outcomes are cognitive function (self-report and objective), emotional function, and pain. RESULTS: We began recruitment in July 2022 and recruited 37 participants across 4 cohorts. Of them, all (n=37, 100%) have completed the baseline assessment, 26 (70%) have completed the posttest assessment, and 9 (24%) are actively enrolled in the intervention (total dropout: n=2, 5%). In the three cohorts (26/37, 70%) that have completed the AB or HEP, 26 (100%) participants completed all 8 group sessions (including minimal makeups), and watch adherence (1937/2072, 93.48%, average across ActiGraph and Fitbit devices) has been excellent. The fourth cohort is ongoing (9/37, 24%), and we plan to complete enrollment by March 2026. CONCLUSIONS: We aim to establish the efficacy of the AB program over a time-matched and dose-matched control in a live video-based trial and test the mechanisms through theoretically driven mediators and moderators. Findings will inform the development of a future multisite effectiveness-implementation trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05373745; https://classic.clinicaltrials.gov/ct2/show/NCT05373745. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47319.

Central Executive Network and Executive Function in Patients With Alzheimer's Disease and Healthy Individuals: Meta-Analysis of Structural and Functional MRI.

OBJECTIVE: The neural architecture of executive function is of interest given its utility as a transdiagnostic predictor of adaptive functioning. However, a gap exists in the meta-analytic literature assessing this relationship in neuropsychiatric populations, concordance between structural and functional architecture, and the relationship with neuropsychological assessment of executive function. Given the importance of the central executive network (CEN) in Alzheimer's disease, this population may be useful in understanding this relationship in Alzheimer's disease pathology. METHODS: A meta-analysis of studies (k=21) was conducted to elucidate the relationship between executive function and CEN for structural architecture (k=10; N=1,027) among patients with Alzheimer's disease (k=6; N=250) and healthy control subjects (HCs) (k=4; N=777) and for functional architecture (k=11; N=522) among patients with Alzheimer's disease (k=6; N=306) and HCs (k=5; N=216). Random-effects modeling was used to increase accuracy of conclusions about population means. RESULTS: Analyses revealed a positive brain-behavior relationship (pr=0.032, 95% CI=0.07, 0.54), although there was a lack of statistically significant heterogeneity between functional and structural neuroimaging (Q=9.89, p=0.971, I2=0.00%) and between the Alzheimer's and HC groups in functional (Q=8.18, p=0.612, I2=0.00%) and structural (Q=1.60, p=0.996, I2=0.00%) neuroimaging. Similarly, a lack of statistically significant heterogeneity was revealed between functional and structural neuroimaging among patients with Alzheimer's disease (Q=3.59, p=0.980, I2=0.00%) and HCs (Q=3.67, p=0.885, I2=0.00%). CONCLUSIONS: Structural and functional imaging in the CEN are predictive of executive function performance among patients with Alzheimer's disease and HCs. Regardless of how the CEN is affected, behavior is correlated to the degree to which the CEN is affected. Findings are significant in the context of methodological decisions in multimodal neuroimaging research.

The central executive network and executive function in healthy and persons with schizophrenia groups: a meta-analysis of structural and functional MRI.

This meta-analysis evaluated the extent to which executive function can be understood with structural and functional magnetic resonance imaging. Studies included structural in schizophrenia (k = 8; n = 241) and healthy controls (k = 12; n = 1660), and functional in schizophrenia (k = 4; n = 104) and healthy controls (k = 12; n = 712). Results revealed a positive association in the brain behavior relationship when pooled across schizophrenia and control samples for structural (pr = 0.27) and functional (pr = 0.29) modalities. Subgroup analyses revealed no significant difference for functional neuroimaging (pr = .43, 95%CI = -.08-.77, p = .088) but with structural neuroimaging (pr = .37, 95%CI = -.08-.69, p = .015) the association to executive functions is lower in the control group. Subgroup analyses also revealed no significant differences in the strength of the brain-behavior relationship in the schizophrenia group (pr = .59, 95%CI = .58-.61, p = .881) or the control group (pr = 0.19, 95%CI = 0.18-0.19, p = 0.920), suggesting concordance.

Human and pigeon suboptimal choice.

Many studies have shown that pigeons will sometimes behave suboptimally by choosing an option that provides food less frequently over one that provides food more frequently. The critical factor in driving suboptimal behavior in these procedures is that the delayed outcomes are differentially signaled on the suboptimal alternative, but not the optimal alternative. Although this procedure is frequently cited as potentially analogous to human gambling, there is little empirical data to evaluate this assertion. The present study tested both pigeon (Experiment 1) and human (Experiment 2) subjects with a suboptimal choice task. Subjects chose between a suboptimal alternative that provided a large reinforcer 20% of the time and an optimal alternative that always provided a small reinforcer. Stimuli presented during the delays signaled the outcomes on the suboptimal alternative in some conditions. When outcomes were signaled, pigeons chose the suboptimal alternative more frequently than did humans. When the outcomes were not signaled, pigeons' choices became more optimal, but humans' choices did not. Humans' suboptimal choice was unrelated to performance on a probability discounting task. Overall, these findings suggest that although both pigeons and humans can choose suboptimally, more research is needed in order to determine whether non-human performance on this task can serve as a model for human gambling.