Yuan Han, Young Kymberly D, Phillips Raquel, Zotev Vadim, Misaki Masaya, Bodurka Jerzy
1 Laureate Institute for Brain Research , Tulsa, Oklahoma.
Brain Connect. 2014 Nov;4(9):690-701. doi: 10.1089/brain.2014.0262.
Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD) and normalize with remission. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training with the goal of upregulating amygdala activity during recall of happy autobiographical memories (AMs) has been suggested, and recently explored, as a novel therapeutic approach that resulted in improvement in self-reported mood in depressed subjects. In this study, we assessed the possibility of sustained brain changes as well as the neuromodulatory effects of rtfMRI-nf training of the amygdala during recall of positive AMs in MDD and matched healthy subjects. MDD and healthy subjects went through one visit of rtfMRI-nf training. Subjects were assigned to receive active neurofeedback from the left amygdale (LA) or from a control region putatively not modulated by AM recall or emotion regulation, that is, the left horizontal segment of the intraparietal sulcus. To assess lasting effects of neurofeedback in MDD, the resting-state functional connectivity before and after rtfMRI-nf in 27 depressed subjects, as well as in 27 matched healthy subjects before rtfMRI-nf was measured. Results show that abnormal hypo-connectivity with LA in MDD is reversed after rtfMRI-nf training by recalling positive AMs. Although such neuromodulatory changes are observed in both MDD groups receiving feedback from respective active and control brain regions, only in the active group are larger decreases of depression severity associated with larger increases of amygdala connectivity and a significant, positive correlation is found between the connectivity changes and the days after neurofeedback. In addition, active neurofeedback training of the amygdala enhances connectivity with temporal cortical regions, including the hippocampus. These results demonstrate lasting brain changes induced by amygdala rtfMRI-nf training and suggest the importance of reinforcement learning in rehabilitating emotion regulation in depression.
在重度抑郁症（MDD）中，杏仁核对积极刺激的血流动力学反应减弱，且在症状缓解时恢复正常。实时功能磁共振成像神经反馈（rtfMRI-nf）训练旨在在回忆愉快的自传体记忆（AMs）时上调杏仁核活动，这一训练方法已被提出并在近期得到探索，被视为一种新型治疗方法，可改善抑郁症患者的自我报告情绪。在本研究中，我们评估了MDD患者和匹配的健康受试者在回忆积极AMs期间，rtfMRI-nf训练杏仁核后大脑持续变化的可能性以及神经调节作用。MDD患者和健康受试者均接受了一次rtfMRI-nf训练。受试者被分配接受来自左侧杏仁核（LA）的主动神经反馈，或来自一个假定不受AMs回忆或情绪调节影响的控制区域的反馈，即顶内沟的左侧水平段。为评估神经反馈对MDD的持久影响，我们测量了27名抑郁症患者在rtfMRI-nf前后的静息态功能连接，以及27名匹配的健康受试者在rtfMRI-nf前的静息态功能连接。结果显示，通过回忆积极AMs，rtfMRI-nf训练后MDD患者中与LA的异常低连接性得到逆转。尽管在接受来自各自活跃和控制脑区反馈的两个MDD组中均观察到这种神经调节变化，但仅在活跃组中，抑郁严重程度的更大降低与杏仁核连接性的更大增加相关，并且在连接性变化与神经反馈后的天数之间发现了显著的正相关。此外，对杏仁核的主动神经反馈训练增强了与颞叶皮质区域（包括海马体）的连接性。这些结果证明了杏仁核rtfMRI-nf训练引起的大脑持久变化，并表明强化学习在恢复抑郁症患者情绪调节中的重要性。
