Amygdala functional dysconnectivity lies at the heart of the pathophysiology of bipolar disorder (BD). Recent preclinical studies suggest that the amygdala is a heterogeneous group of nuclei, whose specific connectivity could drive positive or negative emotional valence. We investigated functional connectivity (FC) changes within these circuits emerging from each amygdala’s subdivision in 127 patients with BD in different mood states and 131 healthy controls (HC), who underwent resting-state functional MRI. FC was evaluated between lateral and medial nuclei of amygdalae, and key subcortical regions of the emotion processing network: anterior and posterior parts of the hippocampus, and core and shell parts of the nucleus accumbens. FC was compared across groups, and subgroups of patients depending on their mood states, using linear mixed models. We also tested correlations between FC and depression (MADRS) and mania (YMRS) scores. We found no difference between the whole sample of BD patients vs. HC but a significant correlation between MADRS and right lateral amygdala /right anterior hippocampus, right lateral amygdala/right posterior hippocampus and right lateral amygdala/left anterior hippocampus FC (r = −0.44, r = −0.32, r = −0.27, respectively, all pFDR<0.05). Subgroup analysis revealed decreased right lateral amygdala/right anterior hippocampus and right lateral amygdala/right posterior hippocampus FC in depressed vs. non-depressed patients and increased left medial amygdala/shell part of the left nucleus accumbens FC in manic vs non-manic patients. These results demonstrate that acute mood states in BD concur with FC changes in individual nuclei of the amygdala implicated in distinct emotional valence processing. Overall, our data highlight the importance to consider the amygdala subnuclei separately when studying its FC patterns including patients in distinct homogeneous mood states.

杏仁核功能失调是双相情感障碍 (BD) 病理生理学的核心。最近的临床前研究表明，杏仁核是一组异质的细胞核，其特定的连接性可以驱动积极或消极的情绪效价。我们研究了 127 名处于不同情绪状态的 BD 患者和 131 名接受静息态功能 MRI 的健康对照者 (HC) 中每个杏仁核细分中出现的这些回路内的功能连接 (FC) 变化。 FC 在杏仁核的外侧核和内侧核以及情绪处理网络的关键皮质下区域（海马的前部和后部以及伏隔核的核心和外壳部分）之间进行评估。使用线性混合模型，根据患者的情绪状态，对不同组和亚组的 FC 进行比较。我们还测试了 FC 与抑郁症 (MADRS) 和躁狂症 (YMRS) 分数之间的相关性。我们发现 BD 患者与 HC 患者的整个样本之间没有差异，但 MADRS 与右侧杏仁核/右前海马、右侧杏仁核/右后海马和右侧杏仁核/左前海马 FC 之间存在显着相关性（r  = -0.44 ，r  = -0.32，r  = -0.27，分别，所有 pFDR<0.05）。亚组分析显示，与非抑郁患者相比，抑郁患者的右侧杏仁核/右前海马和右侧杏仁核/右后海马 FC 减少，而躁狂患者与非躁狂患者相比，左侧杏仁核/左伏核壳部分 FC 增加。这些结果表明，BD 中的急性情绪状态与杏仁核单个核中的 FC 变化一致，这些变化涉及不同的情绪效价处理。总体而言，我们的数据强调了在研究其 FC 模式（包括处于不同同质情绪状态的患者）时单独考虑杏仁核亚核的重要性。