Dynamic functional connectome configurations underlying working memory deficits in adolescents with early-onset...

Working memory (WM) is a dynamic process linked to whole-brain functional connectome time-varying re-configuration. The neural dynamics underlying WM deficits in adolescents with early-onset schizophrenia (EOS), who have higher genetic loads and immature WM neural substrates, still remain unclear.

We used dynamic voxel-wise degree centrality (dDC) to explore the dynamic profile of whole-brain functional connectome in 51 adolescents with EOS and 45 healthy controls (HCs) during an n-back task. We assessed the group-related dDC time-varying variability and clustered meta-states differences between EOS and HCs. Correlation analysis also applied between the detected areas with clinical symptoms and WM performances, and detected areas further allowed for image transcription analyses.

We did not observe any group-related differences in the dDC time-varying instability. In the clustered dominant state 1, when facing with increased WM loads, EOS showed decreased dDC compared with HCs in the left insula, anterior and posterior lobe of the cerebellum, bilateral inferior parietal lobule, left pons, bilateral superior temporal gyrus, rectus gyrus, precuneus, bilateral inferior frontal gyrus (IFG), etc. Enrichment analysis reveals these detected areas related to synaptic function, neuronal communication, and metabolic processes.

This is the first study to investigate the abnormal time-varying pattern of the whole-brain connectome in EOS during the WM task and its molecular foundation. It demonstrated impaired neural resource allocation between frontoparietal, default-mode, and salience networks and the associated metabolic processes may underlie WM deficits in EOS, which can provide knowledge for targeted interventions and future research.