Distinct and shared therapeutic neural mechanisms of mindfulness-based and social support stress reduction groups in adults with autism spectrum disorder

Abstract

Background: Mindfulness-based stress reduction (MBSR) alleviates depression and anxiety in adults with autism spectrum disorder (ASD); however, underlying therapeutic neural mechanisms and mindfulness-specific effects have yet to be elucidated.

Methods: We randomly assigned adults with ASD to MBSR or social support/education (SE). They completed questionnaires that assessed depression, anxiety, mindfulness traits, autistic traits and executive functioning abilities as well as a self-reflection functional MRI task. We used repeated-measures analysis of covariance (ANCOVA) to evaluate behavioural changes. To identify task-specific connectivity changes, we performed a generalized psychophysiological interactions (gPPI) functional connectivity (FC) analysis on regions of interest (ROIs; insula, amygdala, cingulum and prefrontal cortex [PFC]). We used Pearson correlations to explore brain-behaviour relationships.

Results: Our final sample included 78 adults with ASD - 39 who received MBSR and 39 who received SE. Mindfulness-based stress reduction uniquely improved executive functioning abilities and increased mindfulness traits, whereas both MBSR and SE groups showed reductions in depression, anxiety and autistic traits. Decreases specific to MBSR in insula-thalamus FC were associated with anxiety reduction and increased mindfulness traits, including the trait "nonjudgment;" MBSR-specific decreases in PFC-posterior cingulate connectivity correlated with improved working memory. Both groups showed decreased amygdala-sensorimotor and medial-lateral PFC connectivity, which corresponded with reduced depression.

Limitations: Larger sample sizes and neuropsychological evaluations are needed to replicate and extend these findings.

Conclusion: Together, our findings suggest that MBSR and SE are similarly efficacious for depression, anxiety and autistic traits, whereas MBSR produced additional salutary effects related to executive functioning and mindfulness traits. Findings from gPPI identified shared and distinct therapeutic neural mechanisms, implicating the default mode and salience networks. Our results mark an early step toward the development of personalized medicine for psychiatric symptoms in ASD and offer novel neural targets for future neurostimulation research.

Clinical trial registration: ClinicalTrials.gov identifier NCT04017793.

Figure 1

Regions of interest (ROIs) for seed-based gPPI functional connectivity analysis. ACC = anterior cingulate cortex; FMC = frontal medial cortex; FP = frontal pole; PCC = posterior cingulate cortex; SFG = superior frontal gyrus. Image generated using the Harvard–Oxford human brain atlas tool.

Figure 2

Participant flow chart detailing eligibility and treatment groups as well as participant retention and data attrition. BDI-II = Beck Depression Inventory-II; BRIEF = Behavior Rating Inventory of Executive Function; FFMQ = Five Facets Mindfulness Questionnaire; MBSR = mindfulness-based stress reduction; SE = social support/education; SRS-2 = Social Responsiveness Scale, second edition; STAI = State–Trait Anxiety Inventory.

Figure 3

Behavioural change from preintervention to postintervention for mindfulness-based stress reduction (MBSR) and social support/ education (SE) groups. Error bars indicate standard error of the mean. There was a significant main effect of time shown on Beck Depression Inventory-II (BDI-II), State–Trait Anxiety Inventory (STAI)-2, and Social Responsiveness Scale, second edition (SRS-2) measures, indicating decreased depression, anxiety and autistic traits postintervention for both groups. There was a significant group × time interaction shown on Five Facets Mindfulness Questionnaire (FFMQ) total score, the FFMQ Nonjudgment subscale, and on the Behavior Rating Inventory of Executive Function (BRIEF) Working Memory subscale, indicating MBSR-specific increases in overall mindfulness and nonjudgment and decreases in executive functioning challenges.

Figure 4

Functional connectivity changes: group × time interactions (p_FDR < 0.025). Top: bar graphs adjusted for covariate of classes; bottom left: coronal slice view; bottom right: sagittal slice view or inflated brain of target cluster. (A) Decreased connectivity of the left insula with the bilateral thalamus. (B) Decreased connectivity of the left frontal pole (FP) with lingual gyrus (LG) and posterior cingulate cortex (PCC). FDR = false discovery rate; L = left; MBSR = mindfulness-based stress reduction; R = right; SE = social support/education.

Figure 5

Functional connectivity changes: main effects of time (across all participants; p_FDR < 0.025). Top: bar graphs adjusted for covariate of classes; bottom left: sagittal slice view; bottom right: inflated brain of target clusters. (A) Increased connectivity of the right insula with the right frontal pole (FP). (B) Decreased connectivity of the left superior frontal gyrus (SFG) with the right frontal pole (FP). (C) Decreased connectivity of the right amygdala with the left pre- and post-central gyrus (CG). FDR = false discovery rate; L = left; R = right.

Figure 6

Brain–behaviour scatterplots for connectivity changes specific to mindfulness-based stress reduction (MBSR; p < 0.05). Associations between (A) insula–thalamus connectivity and State–Trait Anxiety Inventory-2 (STAI-2) scores across all participants, (B) insula–thalamus connectivity and Five Facets Mindfulness Questionnaire (FFMQ) total scores across all participants, (C) insula–thalamus connectivity and FFMQ Nonjudgment subscale scores for participants who received the MBSR intervention, and (D) left frontal pole (FP)–posterior cingulate cortex (PCC)/lingual gyrus (LG) connectivity and Behavior Rating Inventory of Executive Function (BRIEF) Working Memory subscale scores for participants who received the MBSR intervention. L = left; SE = social support/education.

Figure 7

Brain–behaviour scatterplots for nonspecific intervention connectivity changes (p < 0.05). Associations between (A) insula–frontal pole (FP) connectivity and Beck Depression Inventory-II (BDI-II) scores across all participants and (B) amygdala–pre/postcentral gyrus (CG) and BDI-II scores across all participants. MBSR = mindfulness-based stress reduction; R = right; SE = social support/education.