Background: Impaired imitation has been found to be an important factor contributing to social communication deficits in individuals with autism spectrum disorder (ASD). It has been hypothesized that the neural correlate of imitation, the mirror neuron system (MNS), is dysfunctional in ASD, resulting in imitation impairment as one of the key behavioral manifestations in ASD. Previous MNS studies produced inconsistent results, leaving the debate of whether “broken” mirror neurons in ASD are unresolved. Methods: This meta-analysis aimed to explore the differences in MNS activation patterns between typically developing (TD) and ASD individuals when they observe biological motions with or without social-emotional components. Effect size signed differential mapping (ES-SDM) was adopted to synthesize the available fMRI data. Results: ES-SDM analysis revealed hyperactivation in the right inferior frontal gyrus and left supplementary motor area in ASD during observation of biological motions. Subgroup analysis of experiments involving the observation of stimuli with or without emotional component revealed hyperactivation in the left inferior parietal lobule and left supplementary motor during action observation without emotional components, whereas hyperactivation of the right inferior frontal gyrus was found during action observation with emotional components in ASD. Subgroup analyses of age showed hyperactivation of the bilateral inferior frontal gyrus in ASD adolescents, while hyperactivation in the right inferior frontal gyrus was noted in ASD adults. Meta-regression within ASD individuals indicated that the right cerebellum crus I activation increased with age, while the left inferior temporal gyrus activation decreased with age. Limitations: This meta-analysis is limited in its generalization of the findings to individuals with ASD by the restricted age range, heterogeneous study sample, and the large within-group variation in MNS activation patterns during object observation. Furthermore, we only included action observation studies which might limit the generalization of our results to the imitation deficits in ASD. In addition, the relatively small sample size for individual studies might also potentially overestimate the effect sizes. Conclusion: The MNS is impaired in ASD. The abnormal activation patterns were found to be modulated by the nature of stimuli and age, which might explain the contradictory results from earlier studies on the “broken mirror neuron” debate.

The clinical effects and neurophysiological mechanisms of prefrontal tDCS and concurrent cognitive remediation training in individuals with autism spectrum disorder (ASD) remain unclear. This two-armed, double-blind, randomized, sham-controlled trial aimed to investigate the beneficial effects of tDCS combined with concurrent cognitive remediation training on adolescents and young adults with ASD. Participants were randomly assigned to either active or sham tDCS groups and received 1.5 mA prefrontal tDCS with left dorsolateral prefrontal cortex (dlPFC) cathode placement and right supraorbital region anode placement for 20 minutes over two consecutive weeks. tDCS was delivered concurrently with a computerized cognitive remediation training program. Social functioning and its underlying cognitive processes, as well as prefrontal resting-state functional connectivity (rsFC), were measured. The results from 41 participants indicated that multisession prefrontal tDCS, compared to sham tDCS, significantly enhanced the social functioning of ASD individuals [F(1,39) = 4.75, p = .035, η_p² = 0.11]. This improvement was associated with enhanced emotion recognition [F(1,39) = 8.34, p = .006, η_p² = 0.18] and cognitive flexibility [F(1,39) = 4.91, p = .033, η_p² = 0.11]. Specifically, this tDCS protocol optimized information processing efficiency [F(1,39) = 4.43, p = .042, η_p² = 0.10], and the optimization showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex (ρ = 0.339, pFDR = .083). Multisession tDCS with left dlPFC cathode placement and right supraorbital region anode placement paired with concurrent cognitive remediation training promoted social functioning in individuals with ASD. This appeared to be associated with the enhancement of the functional connectivity of the right medial PFC, a major hub for flexible social information processing, allowing these individuals to process information more efficiently in response to different social situations. ClinicalTrials.gov (ID: NCT03814083).

Previous behavioral studies show that music listening enhances attention and working memory in both healthy and clinical populations. However, how music listening engages brain functional networks remains elusive due to inconsistent results from previous findings. A meta-analysis of functional magnetic resonance imaging data using seed-based d mapping (SDM) with permutation of subject images was performed. Studies that presented music listening paradigms to healthy individuals were included. Subgroup analyses were performed to investigate the effects of music genres on brain activation. To examine functional network correlates, voxels that were significantly activated by music listening were overlaid onto cortical, subcortical, and striatal network parcellations. Whole-group analysis showed that ventral attention, somatomotor, default, dorsal attention, frontoparietal, and limbic networks significantly coactivated during music listening (familywise error-corrected p < .01). Specifically, music listening activated multiple frontal, temporal, subcortical, and cerebellar regions. Subgroup analyses revealed that classical music, but not songs or simple tunes, activated the limbic network. Meta-regression analysis revealed nonsignificant correlations between years of music training and all brain regions activated during music listening. Music listening bilaterally activated multiple cortical, subcortical, and cerebellar regions encompassing multiple brain networks that were not modulated by music training experience. It is recommended that music listening can be applied to people with neurological disorders to modulate the disordered functional brain networks known to underlie the pathophysiology of these diseases, while future studies may help delineate the effects of music preferences on brain activation patterns among these patients to promote the development of evidence-based medicine. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Previous studies have shown that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASDs). The present study examined whether immunological abnormalities are associated with cognitive and behavioral deficits in children with ASD and whether children with ASD show different immunological biomarkers and brain-derived neurotrophic factor BDNF levels than typically developing (TD) children. Sixteen children with TD and 18 children with ASD, aged 6–18 years, voluntarily participated in the study. Participants’ executive functions were measured using neuropsychological tests, and behavioral measures were measured using parent ratings. Immunological measures were assessed by measuring the participants’ blood serum levels of chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5). Children with ASD showed greater deficits in cognitive functions as well as altered levels of immunological measures when compared to TD children, and their cognitive functions and behavioral deficits were significantly associated with increased CCL5 levels and decreased BDNF levels. These results provide evidence to support the notion that altered immune functions and neurotrophin deficiency are involved in the pathogenesis of ASD.

Few treatment options are available for targeting core symptoms of autism spectrum disorder (ASD). The development of treatments that target common neural circuit dysfunctions caused by known genetic defects, namely, disruption of the excitation/inhibition (E/I) balance, is promising. Transcranial direct current stimulation (tDCS) is capable of modulating the E/I balance in healthy individuals, yet its clinical and neurobiological effects in ASD remain elusive. This double-blind, randomized, sham-controlled trial investigated the effects of multisession cathodal prefrontal tDCS coupled with online cognitive remediation on social functioning, information processing efficiency and the E/I balance in ASD patients aged 14-21 years. Sixty individuals were randomly assigned to receive either active or sham tDCS (10 sessions in total, 20 min/session, stimulation intensity: 1.5 mA, cathode: F3, anode: Fp2, size of electrodes: 25 cm²) combined with 20 min of online cognitive remediation. Social functioning, information processing efficiency during cognitive tasks, and theta- and gamma-band E/I balance were measured one day before and after the treatment. Compared to sham tDCS, active cathodal tDCS was effective in enhancing overall social functioning [F(1, 58) = 6.79, p = .012, η_p² = 0.105, 90% CI: (0.013, 0.234)] and information processing efficiency during cognitive tasks [F(1, 58) = 10.07, p = .002, η_p² = 0.148, 90% CI: (0.034, 0.284)] in these individuals. Electroencephalography data showed that this cathodal tDCS protocol was effective in reducing the theta-band E/I ratio of the cortical midline structures [F(1, 58) = 4.65, p = .035, η_p² = 0.074, 90% CI: (0.010, 0.150)] and that this reduction significantly predicted information processing efficiency enhancement (b = -2.546, 95% BCa CI: [-4.979, -0.113], p = .041). Our results support the use of multisession cathodal tDCS over the left dorsolateral prefrontal cortex combined with online cognitive remediation for reducing the elevated theta-band E/I ratio in sociocognitive information processing circuits in ASD patients, resulting in more adaptive regulation of global brain dynamics that is associated with enhanced information processing efficiency after the intervention.