Brown Vanessa M, Wilson Jonathan, Hallquist Michael N, Szanto Katalin, Dombrovski Alexandre Y
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychology, Pennsylvania State University, State College, PA, USA.
Neuropsychopharmacology. 2020 May;45(6):1034-1041. doi: 10.1038/s41386-020-0632-0. Epub 2020 Feb 8.
Suicide is linked to impaired value-based decision-making and impulsivity, but whether these risk factors share neural underpinnings is unclear. Disrupted ventromedial prefrontal cortex (vmPFC) value signals may underlie this behavioral phenotype. We investigated vmPFC value signals, vmPFC-frontoparietal connectivity, and the impact of impulsivity during decision-making in depressed individuals with and without suicidal behavior. Middle-aged and older adults (n = 116; 35 with a history of suicide attempts, 25 with ideation only, 25 depressed controls with no ideation, and 31 nonpsychiatric controls) completed a decision-making task with drifting reward probabilities during fMRI. Values of choices, estimated by a reinforcement learning model, were regressed against BOLD signal. VmPFC value activation was compared between groups. Moderating effects of impulsivity on vmPFC-frontoparietal connectivity were assessed in nonpsychiatric controls and compared among patient groups. VmPFC value responses in participants with a history of suicide attempts were reduced relative to nonpsychiatric controls (p < 0.05). In nonpsychiatric controls, vmPFC-frontoparietal connectivity was negatively moderated by impulsivity (p < 0.05). This effect was preserved in comparison patient groups but abolished in suicide attempters (p < 0.001). This change in neural connectivity patterns also affected behavior: people with a history of suicide attempts showed a disrupted effect of vmPFC-frontoparietal connectivity, impulsivity, and reinforcement on choice quality (p < 0.001). These effects were specific to vmPFC and not to striatum. In summary, findings from this study largely support disrupted vmPFC value signals in suicidal behavior. In addition, it uncovers an altered pattern of vmPFC-frontoparietal connectivity in impulsive people with suicidal behavior, which may underlie disrupted choice processes in a suicidal crisis.
自杀与基于价值的决策受损和冲动性有关,但这些风险因素是否共享神经基础尚不清楚。腹内侧前额叶皮层(vmPFC)价值信号紊乱可能是这种行为表型的基础。我们研究了有或无自杀行为的抑郁症患者在决策过程中的vmPFC价值信号、vmPFC-额顶叶连接性以及冲动性的影响。中年及老年成年人(n = 116;35例有自杀未遂史,25例仅有自杀意念,25例无自杀意念的抑郁症对照者,以及31例非精神科对照者)在功能磁共振成像(fMRI)期间完成了一项具有漂移奖励概率的决策任务。通过强化学习模型估计的选择价值与血氧水平依赖(BOLD)信号进行回归分析。比较了各组之间的vmPFC价值激活情况。在非精神科对照者中评估了冲动性对vmPFC-额顶叶连接性的调节作用,并在患者组之间进行了比较。有自杀未遂史的参与者的vmPFC价值反应相对于非精神科对照者有所降低(p < 0.05)。在非精神科对照者中,冲动性对vmPFC-额顶叶连接性有负向调节作用(p < 0.05)。在比较患者组中这种效应得以保留,但在自杀未遂者中则消失(p < 0.001)。这种神经连接模式的变化也影响了行为:有自杀未遂史的人在vmPFC-额顶叶连接性、冲动性和强化对选择质量的影响方面表现出紊乱(p < 0.001)。这些效应是vmPFC特有的,而非纹状体。总之,本研究结果在很大程度上支持了自杀行为中vmPFC价值信号的紊乱。此外,它揭示了有自杀行为的冲动人群中vmPFC-额顶叶连接性的改变模式,这可能是自杀危机中选择过程紊乱的基础。