Brain regions showing significant FC are functionally coupled and may reflect components of a single but spatially distributed system (i.e., a large-scale

brain network). Granger causal connectivity is a measure of effective connectivity; the presence of Granger causal connectivity from a region A to another region B implies that the neuronal activity in region A precedes and predicts the neuronal activity that occurs in region B. These two regions, A and B, may not show instantaneous functional coupling that is characteristic of a single large-scale system. Thus, Granger causal analysis (GCA) is a more useful approach to study the causal relationships that may exist across networks. To investigate Alectinib ic50 the “causal” influences between the salience processing and the executive systems, we employed Granger causality analysis in task-free resting-state fMRI. Task-free conditions minimize potentially confounding effects of between-group performance differences and permit the investigation of fundamental components of neurophysiological function. We hypothesized that the “causal” influence of

the rAI over the multimodal brain regions constituting the executive system will be reduced in schizophrenia. We also predicted that any abnormality in the feedforward influence would be accompanied by a reciprocal diminution of the feedback from the executive system Alpelisib price to the rAI, resulting in a dysfunctional salience-execution loop in patients. In addition, using a mediation model, we studied the relationship between the abnormalities

in the functional connectivity of the SN and the “causal” outflow from the salience processing to the executive system. Finally, we investigated whether the illness severity in patients is predicted by the dysfunction of the salience-execution loop. The demographic and clinical characteristics of the sample are presented in Table S1 available online. Patients did not differ from the controls in terms of age (mean (SD) age in patients = 34.5(9.1), controls = 33.5(9.1), t(71) = 0.46, p = 0.65), Non-specific serine/threonine protein kinase gender (females/males = −10/25 in controls; 9/29 in patients, chi-square p = 0.63), handedness (right/left = 33/5 in patients; 31/4 in controls, chi-square p = 0.82), and parental Socioeconomic Scale (SES) score (mean (SD) in patients = 2.4(1.5), controls = 2.1(1.3), t(71) = 0.79, p = 0.43). Patients had a mean current symptom burden of 12.1 units (SD = 7.3; range 1 to 25) measured using the Symptoms and Signs in Psychotic Illness (SSPI) (out of a maximum possible score of 80). In the entire sample (patients and controls, one-sample t test), rAI exerted a significant excitatory influence on the bilateral DLPFC, inferior parietal regions, and left cerebellar crus.