M1 neuroplasticity as a neurophysiological index of depressive symptom severity and treatment associated neural changes: a two-phase cross-sectional and randomized controlled trial

Background Neuroplasticity deficits are a core pathophysiological feature of depression. However, the relationship between neuroplasticity deficits and clinical severity remains poorly characterized. This study investigated this relationship by characterizing primary motor cortex (M1) plasticity across different levels of depressive severity and evaluated its relationship with clinical outcomes following adjunctive acupuncture treatment. Methods This two-phase study first employed a cross-sectional design (Phase I, n = 134) to assess M1 plasticity using paired associative stimulation (PAS) across depression severity levels. Phase II (n = 60) was a randomized controlled trial in which patients with moderate depression received sertraline plus verum acupuncture (St+VA), sertraline plus sham acupuncture (St+SA), or sertraline alone (St) for 6 weeks. Clinical outcomes (HAMD-24) and PAS-induced plasticity were evaluated. Results In Phase I, patients with depression exhibited significantly blunted LTP-like and LTD-like plasticity compared to HCs ( P FDR < 0.001), with greater impairment observed in groups with higher depressive symptom severity. In Phase II, St+VA induced a greater percentage reduction in HAMD-24 scores than St+SA and St alone (both P FDR < 0.01), reduced antidepressant-related side effects, and modulated both PAS25- and PAS10-induced MEP plasticity. Treatment-induced improvement in PAS25-induced MEP plasticity was positively correlated with the percentage reduction in HAMD-24 scores (Spearman’s r ₛ = 0.423, P FDR = 0.006), whereas ΔPAS10-MEP was not significantly associated with clinical improvement. Conclusions Altered M1 neuroplasticity was associated with depressive symptom severity and may serve as a neurophysiological index of depression-related cortical dysfunction. Adjunctive acupuncture enhances therapeutic efficacy in moderate depression, a clinical benefit associated with changes in M1 LTP-like plasticity. Clinical trial number ChiCTR2000039441; ChiCTR2000029915. Clinical trial registry Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ). Registration date October 28, 2020; February 16, 2020.