Altered cortical oxygenation dynamics, impaired cortical recruitment, and network dysconnectivity across the transdiagnostic anxiety spectrum: a systems biology multi-channel fNIRS study.

Background

Anxiety-spectrum disorders (ANSD) are highly prevalent, yet the underlying cortical neurofunctional alterations remain unclear. A systems-biology approach integrating complementary functional near-infrared spectroscopy (fNIRS) measures may provide a more comprehensive characterization of cortical dysfunction across the anxiety spectrum.

Methods

We investigated healthy controls (HC), generalized anxiety disorder (GAD), anxious depression (AD), and anxiety-depression comorbidity (CO) using multichannel fNIRS during a verbal fluency task. Multiple hemodynamic features were extracted, including peak response, temporal hemodynamic variability, β₁ activation, and oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (HbT) signals. Functional connectivity, graph-theoretical network measures, machine-learning classification, and associations with depressive, anxiety, and psychosomatic scores were examined.

Results

Compared with controls, ANSD patients showed reduced task-evoked HbO and HbT responses, a region-specific increase in peak HbR in the right SMA, increased temporal hemodynamic variability, and reduced β₁ activation. Activation deficits were most prominent in bilateral frontopolar and medial prefrontal cortices, with particularly pronounced abnormalities in CO. Functional connectivity was increased, whereas clustering coefficient, nodal local efficiency, and nodal efficiency were reduced, indicating maladaptive hyperconnectivity accompanied by inefficient network organization. The AD and CO groups showed the greatest network disintegration. Temporal hemodynamic variability emerged as the strongest predictor of anxiety, depressive, and psychosomatic symptom severity. Reduced prefrontal activation was significantly associated with higher symptom-domain scores.

Conclusions

This systems-biology analysis identifies convergent abnormalities in cortical oxygenation, recruitment, temporal dynamics, connectivity, and network topology across ANSD, supporting shared but heterogeneous transdiagnostic neurofunctional processes across the anxiety spectrum.