A transdiagnostic group exercise intervention for mental health outpatients in Germany (ImPuls): results of a pragmatic, multisite, block-randomised, phase 3 controlled trial.

BACKGROUND: Globally, mental health conditions pose a substantial burden of disease. Despite the availability of evidence-based pharmacological and psychological treatments, the symptoms of a substantial subgroup of patients do not respond to these interventions, and only a minority of patients have access to them. This study aimed to assess the efficacy of ImPuls, a 6-month transdiagnostic group exercise intervention, plus treatment-as-usual, compared with treatment-as-usual alone in outpatients with various mental disorders. METHODS: In this pragmatic, two-arm, multisite, randomised controlled trial in Germany, ten outpatient rehabilitative and medical care facilities were involved as study sites. Participants were outpatients diagnosed according to ICD-10 with one or more of the following disorders based on structured clinical interviews: moderate or severe depression, primary insomnia, post-traumatic stress disorder (PTSD), panic disorder, or agoraphobia. Participants were required to be aged between 18 years and 65 years, insured by the health insurers Allgemeine Ortskrankenkasse Baden-Württemberg or Techniker Krankenkasse, fluent in German, and without medical contraindications for exercise. Blocks of six participants were randomly allocated to ImPuls plus treatment-as-usual or treatment-as-usual alone (allocation ratio: 1:1), stratified by study site. The randomisation sequence was generated by an external data manager. The team responsible for data collection and management was masked to the randomisation sequence. The ImPuls intervention comprised evidence-based outdoor exercises lasting 30 min, and aimed at achieving at least moderate intensity. It also incorporated behavioural change techniques targeting motivational and volitional determinants of exercise behaviour. Treatment-as-usual was representative of typical outpatient health care in Germany, allowing patients access to any standard treatments. The primary outcome was global symptom severity at 6 months after randomisation, measured using self-report on the Brief Symptom Inventory (BSI-18) and analysed in the intention-to-treat sample. No individuals with lived experience of mental illness were involved in conducting the study or writing the final publication. Safety was assessed in all participants. The trial was registered with the German Clinical Trials Register (DRKS00024152) with a completion date of June 30, 2024. FINDINGS: 600 patients provided informed consent, were recruited to the study, and underwent a diagnostic interview between Jan 1, 2021, and May 31, 2022. Following this, 199 were excluded on the basis of inclusion and exclusion criteria and one withdrew consent during the baseline assessment. Of the 400 eligible participants, 284 (71%) self-identified as female, 106 (27%) self-identified as male, and nine (2%) self-identified as other. The mean age was 42·20 years (SD 13·23; range 19-65). Ethnicity data were not assessed. 287 (72%) participants met the criteria for moderate or severe depression, 81 (20%) for primary insomnia, 37 (9%) for agoraphobia, 46 (12%) for panic disorder, and 72 (18%) for PTSD. 199 participants were allocated to the intervention group of ImPuls plus treatment-as-usual and 201 to the control group of treatment-as-usual alone. 38 (19%) participants did not receive the minimum ImPuls intervention dose. ImPuls plus treatment-as-usual demonstrated superior efficacy to treatment-as-usual alone in reducing global symptom severity, with an adjusted difference on BSI-18 of 4·11 (95% CI 1·74-6·48; d=0·35 [95% CI 0·14-0·56]; p=0·0007) at 6 months. There were no significant differences in the total number of adverse events or serious adverse events between the two groups. There was one serious adverse event (male, torn ligament) related to the intervention. INTERPRETATION: ImPuls is an efficacious transdiagnostic adjunctive treatment in outpatient mental health care. Our findings suggest that exercise therapy should be implemented in outpatient mental health care as an adjunctive transdiagnostic treatment for mental disorders such as depression, insomnia, panic disorder, agoraphobia, and PTSD. Transdiagnostic group exercise interventions might ameliorate the existing disparity in care provision between the many individuals in need of evidence-based treatment and the few who are receiving it. FUNDING: The German Innovation Fund of the Federal Joint Committee of Germany.

Concept and study protocol of the process evaluation of a pragmatic randomized controlled trial to promote physical activity in outpatients with heterogeneous mental disorders-the ImPuls study.

BACKGROUND: Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial. METHODS: The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis. DISCUSSION: The results of our process evaluation will complement the evaluation of effectiveness and cost-effectiveness and will, for example, provide important information about mechanisms of impact, structural prerequisites, or provider qualification that may support the decision-making process of health policy stakeholders. It might contribute to paving the way for exercise programs like ImPuls to be made successively available for patients with heterogeneous mental disorders in the German outpatient mental health care system. TRIAL REGISTRATION: The parent clinical study was registered in the German Clinical Trials Register (ID: DRKS00024152, registered 05/02/2021, https://drks.de/search/en/trial/DRKS00024152 ).

Efficacy and cost-effectiveness of a Transdiagnostic group-based exercise intervention: study protocol for a pragmatic multi-site randomized controlled trial.

BACKGROUND: Mental disorders are prevalent and cause considerable burden of disease. Exercise has been shown to be efficacious to treat major depressive disorders, insomnia, panic disorder with and without agoraphobia and post traumatic stress disorder (PTSD). METHODS: This pragmatic, two arm, multi-site randomised controlled trial will evaluate the efficacy and cost-effectiveness of the manualized, group-based six-months exercise intervention "ImPuls", among physically inactive patients with major depressive disorders, insomnia, panic disorder, agoraphobia and PTSD within a naturalistic outpatient context in Germany. A minimum of 375 eligible outpatients from 10 different study sites will be block-randomized to either ImPuls in addition to treatment as usual (TAU) or TAU only. ImPuls will be conducted by trained exercise therapists and delivered in groups of six patients. The program will combine (a) moderate to vigorous aerobic exercise carried out two-three times a week for at least 30 min with (b) behavior change techniques for sustained exercise behavior change. All outcomes will be assessed pre-treatment, post-treatment (six months after randomization) and at follow-up (12 months after randomization). Primary outcome will be self-reported global symptom severity assessed with the Brief Symptom Inventory (BSI-18). Secondary outcomes will be accelerometry-based moderate to vigorous physical activity, self-reported exercise, disorder-specific symptoms, quality-adjusted life years (QALY) and healthcare costs. Intention-to-treat analyses will be conducted using mixed models. Cost-effectiveness and cost-utility analysis will be conducted using incremental cost-effectiveness and cost-utility ratios. DISCUSSION: Despite its promising therapeutic effects, exercise programs are currently not provided within the outpatient mental health care system in Germany. This trial will inform service providers and policy makers about the efficacy and cost-effectiveness of the group-based exercise intervention ImPuls within a naturalistic outpatient health care setting. Group-based exercise interventions might provide an option to close the treatment gap within outpatient mental health care settings. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (ID: DRKS00024152 , 05/02/2021).

The spatial Stroop effect: a comparison of color-word and position-word interference.

The Stroop effect is one of the most famous examples of interference in human perception. The present study demonstrates that a position Stroop paradigm, comparable to the classical color-word interference paradigm, resulted in the same pattern of interference for the spatial dimension; however, the interference was significantly weaker. By exchanging the original oral response for a manual response in the spatial paradigm, we showed that the verbal component is crucial for the Stroop effect: Manual responses lead to a disappearance of the interference effect. Moreover, with manual responses word position was recognized at the same speed for the baseline condition and for words that were incongruent as well as congruent with the spatial position. The results indicate (1) that the Stoop effect depends heavily on verbal components and (2) that differing processing speeds between reading and position recognition do not serve as a proper explanation for the effect. In addition, the provided paradigm plausibly transfers the classical color-word interference to the spatial dimension.

How delays matter in an oscillatory whole-brain spiking-neuron network model for MEG alpha-rhythms at rest.

In recent years the study of the intrinsic brain dynamics in a relaxed awake state in the absence of any specific task has gained increasing attention, as spontaneous neural activity has been found to be highly structured at a large scale. This so called resting-state activity has been found to be comprised by nonrandom spatiotemporal patterns and fluctuations, and several Resting-State Networks (RSN) have been found in BOLD-fMRI as well as in MEG signal power envelope correlations. The underlying anatomical connectivity structure between areas of the brain has been identified as being a key to the observed functional network connectivity, but the mechanisms behind this are still underdetermined. Theoretical large-scale brain models for fMRI data have corroborated the importance of the connectome in shaping network dynamics, while the importance of delays and noise differ between studies and depend on the models' specific dynamics. In the current study, we present a spiking neuron network model that is able to produce noisy, distributed alpha-oscillations, matching the power peak in the spectrum of group resting-state MEG recordings. We studied how well the model captured the inter-node correlation structure of the alpha-band power envelopes for different delays between brain areas, and found that the model performs best for propagation delays inside the physiological range (5-10 m/s). Delays also shift the transition from noisy to bursting oscillations to higher global coupling values in the model. Thus, in contrast to the asynchronous fMRI state, delays are important to consider in the presence of oscillation.

Bottom up modeling of the connectome: linking structure and function in the resting brain and their changes in aging.

With the increasing availability of advanced imaging technologies, we are entering a new era of neuroscience. Detailed descriptions of the complex brain network enable us to map out a structural connectome, characterize it with graph theoretical methods, and compare it to the functional networks with increasing detail. To link these two aspects and understand how dynamics and structure interact to form functional brain networks in task and in the resting state, we use theoretical models. The advantage of using theoretical models is that by recreating functional connectivity and time series explicitly from structure and pre-defined dynamics, we can extract critical mechanisms by linking structure and function in ways not directly accessible in the real brain. Recently, resting-state models with varying local dynamics have reproduced empirical functional connectivity patterns, and given support to the view that the brain works at a critical point at the edge of a bifurcation of the system. Here, we present an overview of a modeling approach of the resting brain network and give an application of a neural mass model in the study of complexity changes in aging.

Bimanual movement control is moderated by fixation strategies.

Our study examined the effects of performing a pointing movement with the left hand on the kinematics of a simultaneous grasping movement executed with the right hand. We were especially interested in the question of whether both movements can be controlled independently or whether interference effects occur. Since previous studies suggested that eye movements may play a crucial role in bimanual movement control, the effects of different fixation strategies were also studied. Human participants were either free to move their eyes (Experiment 1) or they had to fixate (Experiment 2) while doing the task. The results show that bimanual movement control differed fundamentally depending on the fixation condition: if free viewing was allowed, participants tended to perform the task sequentially, as reflected in grasping kinematics by a delayed grip opening and a poor adaptation of the grip to the object properties for the duration of the pointing movement. This behavior was accompanied by a serial fixation of the targets for the pointing and grasping movements. In contrast, when central fixation was required, both movements were performed fast and with no obvious interference effects. The results support the notion that bimanual movement control is moderated by fixation strategies. By default, participants seem to prefer a sequential behavior in which the eyes monitor what the hands are doing. However, when forced to fixate, they do surprisingly well in performing both movements in parallel.