Lower cerebrovascular reactivity in prefrontal cortex and weaker negative functional connectivity between prefrontal
Lili Huang1, Xin Liu2, Yue Cheng1
1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China; Nanjing Neurology Medical Center, Nanjing 210008, China.
Background:
White matter hyperintensities (WMHs) are associated with higher anxiety or depression (A/D) incidence. We investigated associations of WMHs with A/D, cerebrovascular reactivity (CVR), and functional connectivity (FC) to identify potential pathomechanisms.
Methods:
Participants with WMH (n = 239) and normal controls (NCs, n = 327) were assessed for A/D using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The CVR and FC maps were constructed from resting-state functional MRI. Two-way analysis of covariance with fixed factors A/D and WMH was performed to identify regional CVR abnormalities. Seed-based FC analyses were then conducted on regions with WMH × A/D interaction effects on CVR. Logistic regression models were constructed to examine the utility of these measurements for identifying WMH-related A/D.
Results:
Participants with WMH related A/D exhibited significantly greater CVR in left insula and lower CVR in right superior frontal gyrus (SFG.R), and HAMA scores were negatively correlated with CVR in SFG.R (r = -0.156, P = 0.016). Insula-SFG.R negative FC was significantly weaker in WMH patients with suspected or definite A/D. A model including CVR plus FC changes identified WMH-associated A/D with highest sensitivity and specificity. In contrast, NCs with A/D exhibited greater CVR in prefrontal cortex and stronger FC within the default mode network (DMN) and between the DMN and executive control network.
Limitations:
This cross-sectional study requires validation by longitudinal and laboratory studies.
Conclusions:
Impaired CVR in SFG.R and weaker negative FC between prefrontal cortex and insula may contribute to WMH-related A/D, providing potential diagnostic imaging markers and therapeutic targets.
