Background

Internalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD.

Methods

We examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms.

Results

Three connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms).

Conclusions

The present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual's generating insight into his or her own psychopathology.

We investigated how cognitive neuroscientific studies during the last decade have advanced understanding of cognitive control from adolescence to young adulthood in individuals with autism spectrum disorder (ASD). To do so, we conducted a selective review of the larger structural, resting state, and diffusion imaging studies of brain regions and networks related to cognitive control that have been conducted since 2007 in individuals with ASD and typical development (TYP) ages 10 to 30 years that examined how these regions and networks support behavioral and task-based fMRI performance on tasks assessing cognitive control during this period. Longitudinal structural studies reveal overgrowth of the anterior cingulate (ACC) and slower white matter development in the parietal cortex in adolescents with ASD versus TYP. Cross-sectional studies of the salience, executive control and default mode resting state functional connectivity networks, which mediate cognitive control, demonstrate patterns of connectivity that differ from TYP through adolescence. Finally, white matter tracts underlying these control-related brain regions continue to show reduced diffusion properties compared to TYP. It is thus not surprising that cognitive control tasks performance improves less during adolescence in ASD versus TYP. This review illustrates that a cognitive neuroscientific approach produces insights about the mechanisms of persistent cognitive control deficits in individuals with ASD from adolescence into young adulthood not apparent with neuropsychological methods alone, and draws attention to the great need for longitudinal studies of this period in those with ASD. Further investigation of ACC and fronto-parietal neural circuits may help specify pathophysiology and treatment options.

Background

The degree to which individuals with autism spectrum disorder (ASD) evidence impairments in episodic memory relative to their typically developing (TD) counterparts remains unclear. According to a prominent view, ASD is associated with deficits in encoding associations between items and recollecting precise context details. Here, we evaluated behavioral and neural evidence for this impaired relational binding hypothesis using a task involving relational encoding and recollection during functional magnetic resonance imaging.

Methods

Adolescents and young adults (n_ASD = 47, n_TD = 60) performed the Relational and Item-Specific Encoding task during functional magnetic resonance imaging, including item and associative recognition testing. We modeled functional recruitment within the medial temporal lobes (MTLs), and connectivity between MTL and the posterior medial (PM) network thought to underlie relational memory. The impaired relational binding model would predict a behavioral deficit driven by aberrant recruitment and connectivity of MTL and the PM network.

Results

The ASD and TD groups showed indistinguishable item and associative recognition performance. During relational encoding, the ASD group demonstrated increased hippocampal recruitment, and decreased connectivity between MTL and PM regions relative to the TD group. Within ASD, hippocampal recruitment and MTL-PM connectivity were inversely correlated.

Conclusions

The lack of a behavioral deficit in ASD does not support the impaired relational binding hypothesis. Instead, the current data suggest that increased recruitment of the hippocampus compensates for decreased MTL-PM connectivity to support preserved episodic memory in ASD. These findings suggest a compensatory neurodevelopmental mechanism that may support preserved cognitive domains in ASD: local hyperrecruitment may offset connectivity aberrations in individuals with ASD relative to TD subjects.

Research has observed evidence for both hypo-(supposedly due to a broken mirror neuron system) and hyper-(thought to be the result of deficits in adaptive control) imitation in autism spectrum disorder (ASD). This work sought to adjudicate between these findings using an automatic imitation (AI) paradigm with the novel manipulation of the need to engage adaptive control of imitation. Results demonstrated that ASD participants do not display a specific deficit in AI capability, are able to engage in proactive control of AI, and that relative to a well-matched effector condition, AI is not selectively associated with ASD symptom severity. These data cast doubt upon the notion of impairments in imitation or its control in ASD.

Although autism spectrum disorder (ASD) is characterized by deficits in cognitive control, our previous work has shown that preparatory, goal-directed cognitive processing (proactive control) may be preserved in children with ASD. We investigated whether proactive control is intact in adolescents and young adults with ASD, as well as how symptoms of ASD (repetitive behaviors) and psychopathology (Depressive, Anxiety, and Attention-Deficit/Hyperactivity Problems) are related to proactive control. Participants were adolescents and young adults with ASD (N = 44) and typical development (TD; N = 44). Proactive control was assessed using a picture-word Stroop paradigm where participants named animals depicted in drawings while ignoring a superimposed written animal word. Interference effects (reaction time (RT) differences between more difficult incongruent trials, where animal pictures and words prompted different responses, and simpler congruent trials, where animal pictures and words prompted the same response) were calculated for two versions of the Stroop Task: a mostly congruent (MC) block, where the majority of trials were congruent, and a mostly incongruent (MI) block, where most trials were incongruent. Proactive control was calculated as the reduction in interference in the MI block in comparison to the MC block. Proactive control did not differ between groups, indicating that proactive control is not impaired in adolescents and young adults with ASD. In ASD, depression symptoms were associated with reduced proactive control. Future research should investigate the effects of interventions targeting depression as well as interventions targeting proactive control processes in individuals with ASD and comorbid depression. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Proactive control refers to the active representation of contextual information to bias cognitive processing and facilitate goal-directed behavior. Despite research suggesting that proactive control may be impaired in autism spectrum disorder (ASD), the associations between proactive control and clinical symptoms of ASD remain underspecified. Here, we combined a children's version of the AX Continuous Performance Task (AX-CPT) with gold standard clinical assessments in children with ASD (N = 34) or typical development (TYP; N = 45). After controlling for full-scale IQ (FSIQ), measures of proactive control were similar between ASD and TYP. However, specifically within ASD we observed paradoxical relationships between proactive control and clinical symptoms. Increased reliance on proactive control was associated with reduced attention problems and increased restricted and repetitive behaviors in ASD. Therefore, proactive control appears to represent a double-edged sword in ASD: improved attentional control at the cost of heightened behavioral inflexibility. This represents a compelling and new characterization of the specific association between cognitive control processes isolated in computerized laboratory tasks and the multidimensional cognitive symptoms characteristic of ASD. (PsycINFO Database Record

Background

It remains unclear whether executive control (EC) deficits in autism spectrum disorder (ASD) represent a failure in proactive EC (engaged and maintained before a cognitively demanding event) or in reactive EC (engaged transiently as the event occurs). We addressed this question by administering a paradigm investigating components of EC in a sample of individuals with ASD and typically developing individuals during functional magnetic resonance imaging.

Methods

During functional magnetic resonance imaging, 141 participants (64 ASD, 77 typically developing) completed a rapid preparing to overcome prepotency task that required participants to respond to an arrow probe based on the color of an initially presented cue. We examined functional recruitment and connectivity in the frontoparietal task control, cingulo-opercular task control, salience, and default mode networks during cue and probe phases of the task.

Results

ASD participants showed evidence of behavioral EC impairment. Analyses of functional recruitment and connectivity revealed that ASD participants showed significantly greater activity during the cue in networks associated with proactive control processes, but on the less cognitively demanding trials. On the more cognitively demanding trials, cue activity was similar across groups. During the probe, connectivity between regions associated with reactive control processes was uniquely enhanced on more-demanding (relative to less-demanding) trials in individuals with ASD but not in typically developing individuals.

Conclusions

The current data suggest that rather than arising from a specific failure to engage proactive or reactive forms of EC, the deficits in EC commonly observed in ASD may be due to reduced proactive EC and a consequent overreliance on reactive EC on more cognitively demanding tasks.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses¹. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset^2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.