Major depressive disorder (MDD), anxiety disorders (ANX), and chronic pain (CP) are closely-related disorders with both high degrees of comorbidity among them and shared risk factors. Considering this multi-level overlap, but also the distinct phenotypes of the disorders, we hypothesized both common and disorder-specific changes of large-scale brain systems, which mediate neural mechanisms and impaired behavioral traits, in MDD, ANX, and CP. To identify such common and disorder-specific brain changes, we conducted a transdiagnostic, multimodal meta-analysis of structural and functional MRI-studies investigating changes of gray matter volume (GMV) and intrinsic functional connectivity (iFC) of large-scale intrinsic brain networks across MDD, ANX, and CP. The study was preregistered at PROSPERO (CRD42019119709). 320 studies comprising 10,931 patients and 11,135 healthy controls were included. Across disorders, common changes focused on GMV-decrease in insular and medial-prefrontal cortices, located mainly within the so-called default-mode and salience networks. Disorder-specific changes comprised hyperconnectivity between default-mode and frontoparietal networks and hypoconnectivity between limbic and salience networks in MDD; limbic network hyperconnectivity and GMV-decrease in insular and medial-temporal cortices in ANX; and hypoconnectivity between salience and default-mode networks and GMV-increase in medial temporal lobes in CP. Common changes suggested a neural correlate for comorbidity and possibly shared neuro-behavioral chronification mechanisms. Disorder-specific changes might underlie distinct phenotypes and possibly additional disorder-specific mechanisms.

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Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala – the brain’s “salience detector” – while processing emotional faces vs. shapes was tested in 16 autistic and 21 non-autistic women by fMRI in a placebo-controlled, within-subjects, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35 voxel cluster, MNI coordinates of peak voxel= -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not non-autistic women (mean change =+0.003%, t=0.153, ptukey=0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin’s effects on the amygdala to specifically include autistic women and specify the subregion of the effect.

Sensory sensitivities occur in up to 90% of autistic individuals. With the recent inclusion of sensory symptoms in the diagnostic criteria for autism, there is a current need to develop neural hypotheses related to autistic sensory perception. Using activation likelihood estimation (ALE), we meta-analysed 52 task-based fMRI studies investigating differences between autistic (n=891) and control (n=967) participants during non-social sensory perception. During complex perception, autistic groups showed more activity in the secondary somatosensory and occipital cortices, insula, caudate, superior temporal gyrus, and inferior parietal lobule, while control groups showed more activity in the frontal and parietal regions. During basic sensory processing, autistic groups showed hyperactivity in the lateral occipital cortex, primary somatosensory and motor cortices, insula, caudate, and thalamus, while controls showed heightened activity in the precentral gyrus, middle frontal gyrus, precuneus, and anterior cingulate cortex. We conclude that autistic individuals, on average, show distinct engagement of sensory-related brain networks during sensory perception. These findings may help guide future research to focus on relevant neurobiological mechanisms underpinning the autistic experience.

Discriminating between similar scenes proves to be a remarkably demanding task due to the limited capacity of our visual cognitive processes. Here we examine how visual scene discrimination is modulated by perceptual differences arising from neurodiversity. A large sample of autistic (n=140) and typical (n=147) participants completed two visual scene discrimination experiments online. Each experiment consisted of “match” (identical scenes) and “mismatch” (subtle differences between scenes) conditions. In both experiments, we found strong evidence for an interaction between group and task condition. Specifically, when compared to typical controls, autistic individuals were on average more accurate at identifying subtle differences between scenes. Taken together, our findings suggest differential and superior processing of contextual expectations in autism. This is consistent with both, classic cognitive theories- such as weak central coherence, enhanced perceptual function, and hyper-systemising- and more recent Bayesian explanations of autistic perception.