The Relationship between Fearfulness, GABA+, and Fear-Related BOLD Responses in the Insula

The inhibitory neurotransmitter GABA plays a crucial role in anxiety and fear, but its relationship to brain activation during fear reactions is not clear. Previous studies suggest that GABA agonists lead to an attenuation of emotion-processing related BOLD signals in the insula. The aim of this study was to investigate the relationship between GABA concentration and fear-related BOLD responses in this region. In 44 female participants with different levels of fearfulness, GABA concentration in the left insula was measured using a GABA+ MRS acquisition during rest; additionally, BOLD signals were obtained during performance of a fear provocation paradigm. Fearfulness was not associated with GABA+ in the left insula, but could predict fear-related BOLD responses in a cluster in the left anterior insula. The BOLD signal change in this cluster did not correlate with GABA+ concentration. However, we found a significant positive correlation between GABA+ concentration and fear-related BOLD responses in a different cluster that included parts of the left insula, amygdala and putamen. Our findings indicate that low insular GABA concentration is not a predisposition for fearfulness, and that several factors influence whether a correlation between GABA and BOLD can be found.

抑制性神经递质γ-氨基丁酸（GABA）在焦虑与恐惧反应中发挥关键作用，但其与恐惧反应过程中的脑激活水平的关联尚未明确。既往研究表明，GABA受体激动剂可减弱脑岛（insula）内与情绪加工相关的血氧水平依赖（Blood Oxygen Level Dependent, BOLD）信号。本研究旨在探究左侧脑岛内GABA浓度与该脑区恐惧相关BOLD响应之间的关联。本研究纳入44名恐惧特质水平各异的女性受试者，在静息状态下通过GABA+磁共振波谱（Magnetic Resonance Spectroscopy, MRS）采集技术测量左侧脑岛的GABA浓度；同时，在执行恐惧诱发范式期间采集受试者的BOLD信号。恐惧特质水平与左侧脑岛内的GABA+浓度无显著相关性，但可预测左侧前脑岛某一激活簇内的恐惧相关BOLD响应。该激活簇内的BOLD信号变化与GABA+浓度未呈现相关性。然而，本研究在包含左侧脑岛、杏仁核（amygdala）及壳核（putamen）部分区域的另一激活簇中，发现GABA+浓度与恐惧相关BOLD响应之间存在显著正相关。本研究结果显示，较低的脑岛GABA浓度并非恐惧特质的易感因素，且多种因素会影响GABA与BOLD信号之间关联的检出情况。