Music for autism: a protocol for an international randomized crossover trial on music therapy for children with autism.

The notion of a connection between autism and music is as old as the first reported cases of autism, and music has been used as a therapeutic tool for many decades. Music therapy holds promise as an intervention for individuals with autism, harnessing their strengths in music processing to enhance communication and expression. While previous randomized controlled trials have demonstrated positive outcomes in terms of global improvement and quality of life, their reliance on psychological outcomes restricts our understanding of underlying mechanisms. This paper introduces the protocol for the Music for Autism study, a randomized crossover trial designed to investigate the effects of a 12-week music therapy intervention on a range of psychometric, neuroimaging, and biological outcomes in school-aged children with autism. The protocol builds upon previous research and aims to both replicate and expand upon findings that demonstrated improvements in social communication and functional brain connectivity following a music intervention. The primary objective of this trial is to determine whether music therapy leads to improvements in social communication and functional brain connectivity as compared to play-based therapy. In addition, secondary aims include exploring various relevant psychometric, neuroimaging, and biological outcomes. To achieve these objectives, we will enroll 80 participants aged 6-12 years in this international, assessor-blinded, crossover randomized controlled trial. Each participant will be randomly assigned to receive either music therapy or play-based therapy for a period of 12 weeks, followed by a 12-week washout period, after which they will receive the alternate intervention. Assessments will be conducted four times, before and after each intervention period. The protocol of the Music for Autism trial provides a comprehensive framework for studying the effects of music therapy on a range of multidimensional outcomes in children with autism. The findings from this trial have the potential to contribute to the development of evidence-based interventions that leverage strengths in music processing to address the complex challenges faced by individuals with autism. Clinical Trial Registration: Clinicaltrials.gov identifier NCT04936048.

Pattern classification based on the amygdala does not predict an individual's response to emotional stimuli.

Functional magnetic resonance imaging (fMRI) studies have often recorded robust univariate group effects in the amygdala of subjects exposed to emotional stimuli. Yet it is unclear to what extent this effect also holds true when multi-voxel pattern analysis (MVPA) is applied at the level of the individual participant. Here we sought to answer this question. To this end, we combined fMRI data from two prior studies (N = 112). For each participant, a linear support vector machine was trained to decode the valence of emotional pictures (negative, neutral, positive) based on brain activity patterns in either the amygdala (primary region-of-interest analysis) or the whole-brain (secondary exploratory analysis). The accuracy score of the amygdala-based pattern classifications was statistically significant for only a handful of participants (4.5%) with a mean and standard deviation of 37% ± 5% across all subjects (range: 28-58%; chance-level: 33%). In contrast, the accuracy score of the whole-brain pattern classifications was statistically significant in roughly half of the participants (50.9%), and had an across-subjects mean and standard deviation of 49% ± 6% (range: 33-62%). The current results suggest that the information conveyed by the emotional pictures was encoded by spatially distributed parts of the brain, rather than by the amygdala alone, and may be of particular relevance to studies that seek to target the amygdala in the treatment of emotion regulation problems, for example via real-time fMRI neurofeedback training.

Effects of Multisession Transcranial Direct Current Stimulation on Stress Regulation and Emotional Working Memory: A Randomized Controlled Trial in Healthy Military Personnel.

OBJECTIVES: Top-down stress regulation, important for military operational performance and mental health, involves emotional working memory and the dorsolateral prefrontal cortex (DLPFC). Multisession transcranial direct current stimulation (tDCS) applied over the DLPFC during working memory training has been shown to improve working memory performance. This study tested the hypothesis that combined tDCS with working memory training also improves top-down stress regulation. However, tDCS response differs between individuals. Resting-state electrophysiological brain activity was post hoc explored as a possible predictor of tDCS response. The predictive value of the ratio between slow-wave theta oscillations and fast-wave beta oscillations (theta/beta ratio) was examined, together with the previously identified tDCS response predictors age, education, and baseline working memory performance. MATERIALS AND METHODS: Healthy military service members (n = 79) underwent three sessions of real or sham tDCS over the right DLPFC (anode: F4, cathode: behind C2) at 2 mA for 20 minutes during emotional working memory training (N-back task). At baseline and within a week after the tDCS training sessions, stress regulation was assessed by fear-potentiated startle responses and subjective fear in a threat-of-shock paradigm with instructed emotional downregulation. Results were analyzed in generalized linear mixed-effects models. RESULTS: Threat-of-shock responses and emotional working memory performance showed no significant group-level effects of the real vs sham tDCS training intervention (p > 0.07). In contrast, when considering baseline theta/beta ratios or the other tDCS response predictors, exploratory results showed a trait-dependent beneficial effect of tDCS on emotional working memory training performance during the first session (p < 0.01). CONCLUSIONS: No evidence was found for effectivity of the tDCS training intervention to improve stress regulation in healthy military personnel. The emotional working memory training results emphasize the importance of studying the effects of tDCS in relation to individual differences. CLINICAL TRIAL REGISTRATION: This study was preregistered on September 16, 2019, at the Netherlands Trial Register (www.trialregister.nl) with ID: NL8028.

Spontaneous brain activity, graph metrics, and head motion related to prospective post-traumatic stress disorder trauma-focused therapy response.

Introduction: Trauma-focused psychotherapy for post-traumatic stress disorder (PTSD) is effective in about half of all patients. Investigating biological systems related to prospective treatment response is important to gain insight in mechanisms predisposing patients for successful intervention. We studied if spontaneous brain activity, brain network characteristics and head motion during the resting state are associated with future treatment success. Methods: Functional magnetic resonance imaging scans were acquired from 46 veterans with PTSD around the start of treatment. Psychotherapy consisted of trauma-focused cognitive behavioral therapy (tf-CBT), eye movement desensitization and reprocessing (EMDR), or a combination thereof. After intervention, 24 patients were classified as treatment responders and 22 as treatment resistant. Differences between groups in spontaneous brain activity were evaluated using amplitude of low-frequency fluctuations (ALFF), while global and regional brain network characteristics were assessed using a minimum spanning tree (MST) approach. In addition, in-scanner head motion was assessed. Results: No differences in spontaneous brain activity and global network characteristics were observed between the responder and non-responder group. The right inferior parietal lobule, right putamen and left superior parietal lobule had a more central position in the network in the responder group compared to the non-responder group, while the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal gyrus and left inferior temporal gyrus had a less central position. In addition, responders showed less head motion. Discussion: These results show that areas involved in executive functioning, attentional and action processes, learning, and visual-object processing, are related to prospective PTSD treatment response in veterans. In addition, these findings suggest that involuntary micromovements may be related to future treatment success.