Case Report of Dual-Site Neurostimulation and Chronic Recording of Cortico-Striatal Circuitry in a Patient With Treatment Refractory Obsessive Compulsive Disorder.

Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of cortico-striatal-thalamo-cortical (CSTC) loops. Deep brain stimulation (DBS) and lesions of CSTC structures have shown promise for treating both OCD and related disorders involving over-expression of automatic/habitual behaviors. Physiologically, we propose that this CSTC hyper-connectivity may be reflected in high synchrony of neural firing between loop structures, which could be measured as coherent oscillations in the local field potential (LFP). Here we report the results from the pilot patient in an Early Feasibility study (https://clinicaltrials.gov/ct2/show/NCT03184454) in which we use the Medtronic Activa PC+ S device to simultaneously record and stimulate in the supplementary motor area (SMA) and ventral capsule/ventral striatum (VC/VS). We hypothesized that frequency-mismatched stimulation should disrupt coherence and reduce compulsive symptoms. The patient reported subjective improvement in OCD symptoms and showed evidence of improved cognitive control with the addition of cortical stimulation, but these changes were not reflected in primary rating scales specific to OCD and depression, or during blinded cortical stimulation. This subjective improvement was correlated with increased SMA and VC/VS coherence in the alpha, beta, and gamma bands, signals which persisted after correcting for stimulation artifacts. We discuss the implications of this research, and propose future directions for research in network modulation in OCD and more broadly across psychiatric disorders.

精神障碍越来越被理解为分布式脑回路中过度连接或连接不足的功能失调。一个典型的例子是强迫症（OCD），它已多次被与皮质 - 纹状体 - 丘脑 - 皮质（CSTC）环路的过度连接相关联。深部脑刺激（DBS）以及CSTC结构的损伤在治疗强迫症和涉及自动/习惯性行为过度表达的相关疾病方面已显示出前景。从生理学角度，我们提出这种CSTC过度连接可能反映在环路结构之间神经放电的高度同步性上，这可以作为局部场电位（LFP）中的相干振荡来测量。在此，我们报告了一项早期可行性研究（https://clinicaltrials.gov/ct2/show/NCT03184454）中试点患者的结果，在该研究中，我们使用美敦力Activa PC + S设备在辅助运动区（SMA）和腹侧内囊/腹侧纹状体（VC/VS）同时进行记录和刺激。我们假设频率不匹配的刺激应该会破坏相干性并减轻强迫症状。患者报告强迫症症状有主观改善，并且有证据表明添加皮质刺激后认知控制得到改善，但这些变化未反映在针对强迫症和抑郁症的主要评定量表中，在盲法皮质刺激期间也未体现。这种主观改善与α、β和γ波段中SMA和VC/VS相干性增加相关，这些信号在校正刺激伪影后仍然存在。我们讨论了这项研究的意义，并为强迫症以及更广泛的精神障碍中的网络调节研究提出了未来的方向。