Function-structure coupling: White matter functional magnetic resonance imaging hyper-activation associates with...

Area of Science:

• Neuroimaging
• Schizophrenia Research
• White Matter Integrity

Background:

• White matter (WM) microstructure deficits are implicated in schizophrenia's brain dysconnectivity hypothesis.
• The precise nature of WM dysfunction in schizophrenia remains unclear.
• Investigating the link between structural deficits and functional disturbances in WM tracts is crucial.

Purpose of the Study:

• To investigate the association between structural deficits and functional disturbances in major WM tracts in schizophrenia.
• To develop and apply a novel skeleton-based WM functional analysis method.
• To examine the relationship between WM function-structure coupling and behavioral assessments.

Main Methods:

• Utilized functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI).
• Developed skeleton-based WM functional analysis for voxel-wise function-structure coupling.
• Measured fractional anisotropy (FA), WM low-frequency oscillation (LFO), and their couplings in patients and controls, with independent database validation.

Main Results:

• Schizophrenia patients exhibited a reversed pattern: higher WM LFO associated with reduced FA in frontotemporal tracts.
• Function-structure association was positive in healthy controls but negative in schizophrenia patients.
• Function-structure dissociation worsened with longer illness duration and severe negative symptoms; WM activations related to cognition and emotion.

Conclusions:

• Revealed significant function-structure dys-coupling in frontotemporal WM in schizophrenia.
• Higher LFO and reduced structural integration in WM may represent a key neuropathological mechanism in schizophrenia.
• Findings highlight the importance of investigating WM integrity and function in schizophrenia.