An Activation Likelihood Estimate Meta-analysis of Thalamocortical Dysconnectivity in Psychosis

Background: Thalamocortical dysconnectivity is hypothesized to underlie the pathophysiology of psychotic disorders, including schizophrenia and bipolar disorder, and individuals at clinical high risk. Numerous studies have examined connectivity networks seeding from the thalamus during rest, revealing a pattern of thalamo-fronto-cerebellar hypoconnectivity and thalamosensory hyperconnectivity. However, given variability in these networks, as well as their relationships with clinical and cognitive symptoms, thalamocortical connectivity's status as a biomarker and treatment target for psychotic disorders remains unclear. Methods: A literature search was performed to identify thalamic seed-based connectivity studies conducted in patients with psychotic disorders. Activation likelihood estimate analysis examined the reported coordinates for hypoconnectivity (healthy control participants > patients with psychosis) and hyperconnectivity (patients with psychosis > healthy control participants). The relationship between hypoconnectivity and hyperconnectivity, as well as their relationships with clinical and cognitive measures, was meta-analyzed. Results: Each activation likelihood estimate included 20 experiments (from 17 publications). Thalamocortical hypoconnectivity was observed in middle frontal, cingulate, and thalamic regions, while hyperconnectivity was observed in motor, somatosensory, temporal, occipital, and insular cortical regions. Meta-analysis of the studies reporting correlations between hypo- and hyperconnectivity showed a strong negative relationship. Meta-analysis of studies reporting correlations between hyperconnectivity and symptoms showed small but significant positive relationships. Conclusions: Activation likelihood estimates of thalamocortical hypoconnectivity revealed a network of prefrontal and thalamic regions, while hyperconnections identified sensory areas. The strong negative relationship between these thalamocortical deflections suggests that they arrive from a common mechanism and may account for aspects of psychosis. These findings identify reliable thalamocortical networks that may guide future studies and serve as crucial treatment targets for psychotic disorders.