Department of Neurological Surgery, Neurological Institute, Columbia University, New York, New York.
College of Physicians and Surgeons, Columbia University, New York, New York.
JAMA Psychiatry. 2015 Feb;72(2):127-35. doi: 10.1001/jamapsychiatry.2014.2216.
Approximately 10% of patients with obsessive-compulsive disorder (OCD) have symptoms that are refractory to pharmacologic and cognitive-behavioral therapies. Neurosurgical interventions can be effective therapeutic options in these patients, but not all individuals respond. The mechanisms underlying this response variability are poorly understood.
To identify neuroanatomical characteristics on preoperative imaging that differentiate responders from nonresponders to dorsal anterior cingulotomy, a neurosurgical lesion procedure used to treat refractory OCD.
DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed preoperative T1 and diffusion magnetic resonance imaging sequences from 15 patients (9 men and 6 women) who underwent dorsal anterior cingulotomy. Eight of the 15 patients (53%) responded to the procedure.
We used voxel-based morphometry (VBM) and diffusion tensor imaging to identify structural and connectivity variations that could differentiate eventual responders from nonresponders. The VBM and probabilistic tractography metrics were correlated with clinical response to the cingulotomy procedure as measured by changes in the Yale-Brown Obsessive Compulsive Scale score.
Voxel-based morphometry analysis revealed a gray matter cluster in the right anterior cingulate cortex, anterior to the eventual lesion, for which signal strength correlated with poor response (P = .017). Decreased gray matter in this region of the dorsal anterior cingulate cortex predicted improved response (mean [SD] gray matter partial volume for responders vs nonresponders, 0.47 [0.03] vs 0.66 [0.03]; corresponding to mean Yale-Brown Obsessive Compulsive Scale score change, -60% [19] vs -11% [9], respectively). Hemispheric asymmetry in connectivity between the eventual lesion and the caudate (for responders vs nonresponders, mean [SD] group laterality for individual lesion seeds, -0.79 [0.18] vs -0.08 [0.65]; P = .04), putamen (-0.55 [0.35] vs 0.50 [0.33]; P = .001), thalamus (-0.82 [0.19] vs 0.41 [0.24]; P = .001), pallidum (-0.78 [0.18] vs 0.43 [0.48]; P = .001), and hippocampus (-0.66 [0.33] vs 0.33 [0.18]; P = .001) also correlated significantly with clinical response, with increased right-sided connectivity predicting greater response.
We identified features of anterior cingulate cortex structure and connectivity that predict clinical response to dorsal anterior cingulotomy for refractory OCD. These results suggest that the variability seen in individual responses to a highly consistent, stereotyped procedure may be due to neuroanatomical variation in the patients. Furthermore, these variations may allow us to predict which patients are most likely to respond to cingulotomy, thereby refining our ability to individualize this treatment for refractory psychiatric disorders.
大约 10%的强迫症 (OCD) 患者对药物和认知行为疗法有反应。神经外科干预可以是这些患者有效的治疗选择，但并非所有患者都有反应。这种反应差异的机制尚不清楚。
确定术前影像学上的神经解剖学特征，这些特征可以区分背侧前扣带切开术的反应者和无反应者，背侧前扣带切开术是一种用于治疗难治性 OCD 的神经外科损伤程序。
设计、设置和参与者：我们回顾性分析了 15 名患者（9 名男性和 6 名女性）的术前 T1 和扩散磁共振成像序列，这些患者接受了背侧前扣带切开术。15 名患者中有 8 名（53%）对该手术有反应。
我们使用基于体素的形态测量学（VBM）和扩散张量成像来识别可能区分最终反应者和无反应者的结构和连接变化。VBM 和概率轨迹分析指标与耶鲁-布朗强迫症量表评分变化衡量的扣带回切开术的临床反应相关。
基于体素的形态测量学分析显示，右侧前扣带皮层的一个灰质簇，位于最终损伤的前方，其信号强度与不良反应相关（P =.017）。背侧前扣带皮层这一区域的灰质减少预测了更好的反应（反应者与无反应者的灰质部分体积中位数[标准差]，分别为 0.47 [0.03]和 0.66 [0.03]；相应的耶鲁-布朗强迫症量表评分变化中位数[标准差]，分别为-60%[19]和-11%[9]）。反应者与无反应者之间最终损伤与尾状核之间的连接的半球不对称性（对于反应者与无反应者，个体损伤种子的组侧性中位数[标准差]，分别为-0.79 [0.18]和-0.08 [0.65]；P =.04）、壳核（-0.55 [0.35]和 0.50 [0.33]；P =.001）、丘脑（-0.82 [0.19]和 0.41 [0.24]；P =.001）、苍白球（-0.78 [0.18]和 0.43 [0.48]；P =.001）和海马（-0.66 [0.33]和 0.33 [0.18]；P =.001）也与临床反应显著相关，右侧连接增加预测反应更大。
我们确定了前扣带皮层结构和连接的特征，这些特征可以预测难治性 OCD 背侧前扣带切开术的临床反应。这些结果表明，对高度一致、刻板的手术反应的个体差异可能是由于患者的神经解剖结构差异造成的。此外，这些变化可能使我们能够预测哪些患者最有可能对扣带切开术有反应，从而提高我们为难治性精神疾病进行个体化治疗的能力。
