Verbal fluency and whole-brain functional connectivity of the left inferior frontal gyrus in schizophrenia patients with different long-term outcomes

The analysis of heterogeneity in cognition and brain functioning in patients with schizophrenia seems promising for a deeper understanding of the disorder as well as treatment individualization. As language production and its executive control are disturbed in schizophrenia but may be heterogeneous in severity across patients and related to outcome, we aimed to compare the neuropsychological and neuroimaging measures related to these processes in patients with long-term schizophrenia spectrum disorders (mean illness duration of 20.3 ± 6.0 years) characterized by diverse clinical and functional statuses. Forty-four male patients and 18 age-comparable healthy males participated in the study. The participants performed four verbal fluency tasks (VF) and underwent resting-state fMRI. K-means clustering based on PANSS subscales and the PSP total score allocated patients to subgroups with better (S1; n = 15) and worse (S2; n = 29) outcomes. Between-group differences in VF performance and the whole-brain functional connectivity (FC) of the two seeds (the inferior frontal gyrus and the supplementary motor cortex) in the left hemisphere were analyzed. S1 demonstrated better performance in the letter and non-structured VF conditions compared to S2, and S1 did not differ from the healthy controls. Furthermore, S1 had higher FC between the left inferior frontal gyrus and a region in the left postcentral/precentral gyri and superior parietal lobule compared to S2 and the healthy controls. The latter finding merits attention in the context of resilience mechanisms in schizophrenia patients with more benign outcome