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Right broca homologue mediates the pain-depression circuit: a case-control Functional Near-Infrared Spectroscopy
Jiaren Zheng1,2, Ning Zhu3, Jiaxi Huang4
1Xiamen Key Lab of Psychoradiology and Neuromodulation, Function Testing and Modulation Center for Neurological, West China Hospital, West China Xiamen Hospital, Sichuan University, Xiamen Fujian, 361000, China. 150482573@qq.com.
Background:
Chronic somatic pain (CSP) and major depressive disorder (MDD) frequently co-occur and are associated with poor prognosis. However, the neural circuit mechanisms underlying the modulation of MDD pathology by CSP remain unclear.
Methods:
This case-control study included 129 participants who underwent fNIRS during a verbal fluency task (VFT) and at rest. Participants were divided into three groups (n = 43 each): MDD patients with comorbid CSP (MDD + CSP), MDD patients without CSP (MDD-CSP), and healthy controls (HC). This study aimed to identify CSP-specific neural signatures and examine their mediating role between pain and depression.
Results:
Compared with HC, all MDD patients exhibited reduced activation in the bilateral frontopolar cortex during the task. A key finding was that, relative to both HC and the MDD-only group, the comorbid group showed selectively lower activation in the right-hemispheric Broca's homologue (RH-Broca) (p = 0.003). Pain intensity was negatively correlated with RH-Broca activation (p < 0.001). Mediation analysis revealed a bidirectional mediating effect of RH-Broca activation on the pain-depression relationship: it mediated both the pathway from pain to depression (indirect effect β = 1.17, 95% CI: 0.66-1.71) and the pathway from depression to pain (indirect effect β = 0.13, 95% CI: 0.08-0.18). At rest, the comorbid group displayed hyperactivation in the right frontopolar cortex, whereas the MDD-only group showed alterations in small-world network properties.
Conclusion:
Selective hypoactivation in the right-hemispheric language network, particularly in the RH-Broca, is closely associated with the comorbidity of chronic somatic pain and major depressive disorder and may contribute to their mutual exacerbation. These findings support the view that the RH-Broca serves as a putative neural node connecting pain and depressive symptoms, potentially forming a bidirectional loop in comorbid patients. This neural circuit may represent a promising target for neuromodulation therapy in patients with MDD comorbid with CSP.
