Abnormal functional activation and connectivity in the working memory network in early-onset schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Developmental Psychology

Background:

• Working memory (WM) network disruption is a hallmark of schizophrenia.
• The dorsolateral prefrontal cortex (DLPFC) is crucial for WM and undergoes significant remodeling during adolescence.
• The interplay between WM network development and schizophrenia pathophysiology is not well understood.

Purpose of the Study:

• To investigate DLPFC activation and functional connectivity during WM tasks in early-onset schizophrenia (EOS).
• To compare WM network function in adolescents with EOS versus healthy controls.

Main Methods:

• Functional magnetic resonance imaging (fMRI) was used to measure brain activity.
• Psychophysiological interaction (PPI) analysis assessed functional connectivity.
• Participants completed a two-back WM task.

Main Results:

• EOS patients showed reduced DLPFC, anterior cingulate cortex (ACC), and frontal operculum engagement.
• Reduced DLPFC connectivity within the WM network was observed in EOS patients.
• EOS patients exhibited abnormal DLPFC coupling with the ACC, inferior parietal lobule, and middle occipital gyrus, alongside age-related decreases in DLPFC activity and increased connectivity with the ACC.

Conclusions:

• Adolescents with EOS display dysfunctional engagement and integration within the WM neural network.
• Schizophrenia-related processes appear to affect brain regions undergoing significant late developmental changes, as indicated by abnormal age-related correlations in DLPFC activity and connectivity.