Individuals with autism and intellectual impairments tend to be excluded from research due to their difficulties with methodological compliance. This study focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare children with autism and a IQ ≤ 80 to participate in a study on neurofeedback training (NFT). Seven children (ages 6-8) learned the prerequisite skills identified in a task analysis in an average of 5 h of TAGteach training, indicating that this is a feasible method of preparing intellectually-impaired children with autism to participate in NFT and task-dependent electroencephalography measures. TAGteach may thus have the potential to augment this population's ability to participate in less accessible treatments and behavioral neuroscientific studies.

Importance

Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition.

Objective

To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS).

Design, setting, and participants

Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ.

Main outcomes and measures

Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures.

Results

Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction.

Conclusions and relevance

Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.

We sought to examine, via Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) in a case-control design, whether bioenergetic deficits in autism spectrum disorders extend to the brain and muscle. Six cases with autism spectrum disorder with suspected mitochondrial dysfunction (age 6-18 years) and 6 age/sex-matched controls underwent (31)P magnetic resonance spectroscopy. The outcomes of focus were muscle resting phosphocreatine and intracellular pH as well as postexercise phosphocreatine recovery time constant and frontal brain phosphocreatine. Intracellular muscle pH was lower in each autism spectrum disorder case than their matched control (6/6, P = .03; P = .0048, paired t test). Muscle phosphocreatine (5/6), brain phosphocreatine (3/4), and muscle phosphocreatine recovery time constant (3/3) trends were in the predicted direction (not all participants completed each). This study introduces (31)P magnetic resonance spectroscopy as a noninvasive tool for assessment of mitochondrial function in autism spectrum disorder enabling bioenergetic assessment in brain and provides preliminary evidence suggesting that bioenergetic defects in cases with autism spectrum disorder are present in muscle and may extend to brain.

We sought to examine, via Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) in a case-control design, whether bioenergetic deficits in autism spectrum disorders extend to the brain and muscle. Six cases with autism spectrum disorder with suspected mitochondrial dysfunction (age 6-18 years) and 6 age/sex-matched controls underwent (31)P magnetic resonance spectroscopy. The outcomes of focus were muscle resting phosphocreatine and intracellular pH as well as postexercise phosphocreatine recovery time constant and frontal brain phosphocreatine. Intracellular muscle pH was lower in each autism spectrum disorder case than their matched control (6/6, P = .03; P = .0048, paired t test). Muscle phosphocreatine (5/6), brain phosphocreatine (3/4), and muscle phosphocreatine recovery time constant (3/3) trends were in the predicted direction (not all participants completed each). This study introduces (31)P magnetic resonance spectroscopy as a noninvasive tool for assessment of mitochondrial function in autism spectrum disorder enabling bioenergetic assessment in brain and provides preliminary evidence suggesting that bioenergetic defects in cases with autism spectrum disorder are present in muscle and may extend to brain.