Task-Related Controllability of Functional Connectome During a Working Memory Task in Schizophrenia, Bipolar...

Area of Science:

• Neuroscience
• Psychiatry
• Cognitive Science

Background:

• Working memory deficits are common in major psychiatric disorders (MPDs).
• Altered brain state transition control is a potential neural basis for these working memory impairments.
• Understanding shared and disorder-specific alterations in brain controllability is crucial.

Purpose of the Study:

• To investigate shared and illness-specific alterations in brain controllability underlying working memory deficits in MPDs.
• To examine the relationship between controllability, clinical/cognitive characteristics, and genetic/neurotransmitter bases.

Main Methods:

• Functional magnetic resonance imaging (fMRI) data from patients with schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and healthy controls (HCs) during an n-back task.
• Calculation of average and modal controllability for brain regions to assess state transition capacities.
• Investigation of genetic and neurotransmitter associations with altered controllability.

Main Results:

• All MPDs showed reduced modal controllability in the frontoparietal network compared to HCs, with SZ exhibiting the most significant deficit.
• SZ displayed broader reductions in average and modal controllability across cortical networks, including sensory, default mode, and salience networks.
• Affected regions showed preferential gene expression related to synaptic biology and neurotransmitters (glutamate/GABA, dopamine, 5-HT).

Conclusions:

• A common, graded reduction in controllability underlies working memory deficits across MPDs.
• This deficit, particularly pronounced in schizophrenia, is linked to synaptic biology and neurotransmitter systems.
• Altered control of brain state transitions offers a transdiagnostic neural mechanism for working memory impairment in psychiatric disorders.