Department of Psychiatry, University of Pittsburgh, Pittsburgh (Price, Ferrarelli, Kim, Karim, Renard, Kaskie, Degutis, Wears, Brown, Siegle, Wallace, Ahmari); Department of Psychology, Trinity College Dublin, Dublin (Gillan); Department of Cancer Biology, Wake Forest University, Winston-Salem N.C. (Hanlon); Department of Psychiatry and Behavioral Sciences, Duke University, Durham N.C. (Vienneau, Peterchev).
Am J Psychiatry. 2021 May 1;178(5):459-468. doi: 10.1176/appi.ajp.2020.20060821. Epub 2021 Mar 17.
Compulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors "stamped in" through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings.
After a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe.
cTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS.
Experimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.
强迫行为是强迫谱系障碍的核心特征，但也出现在广泛的心理状况中。人们认为，强迫反映了一种未能通过反复练习和短期减轻痛苦来克服“铭刻”的习惯行为的失败。动物模型表明眶额皮层（OFC）在强迫行为中可能起因果作用，但人类研究在很大程度上受到相关设计的限制。本研究的目的是为一个机制模型建立第一个实验证据，以便为进一步的实验工作和最终开发涉及协同生物-行为配对的新型机制治疗提供信息。
在基线评估后，将 69 名有强迫行为障碍的个体随机分为两组，采用双盲、组间设计，接受两种针对左 OFC 的活性刺激之一的单次治疗：间歇性 theta 爆发刺激（iTBS），预计增加 OFC 活动，或连续 TBS（cTBS），预计降低活动（两种情况，110%目标静息运动阈值的 600 个脉冲）。在两种情况下，脑调制与随后的计算机任务配对，该任务提供了在预期的 OFC 增加或减少窗口中克服临床相关习惯（一种过度学习的回避行为）的实践。在 TBS 前后进行了目标参与和针对个体设计的应激实验室探针的强迫行为的功能磁共振成像评估。
cTBS 和 iTBS 以预期的方向调节了 OFC 的激活。与 iTBS 相比，cTBS 在 TBS 后 90 分钟对急性实验室评估的强迫行为产生了有益的影响。这些急性行为效应在 cTBS 后 1 周持续存在。
在习惯克服训练的行为背景下，OFC 的实验性调节影响了强迫行为脆弱性的短期标志物。这些发现有助于描绘一个因果转化模型，作为机制干预开发的初步前奏。
