Lee A Moses, Kist Audrey, Alvarez John, Sellers Kristin K, Khambhati Ankit N, Sugrue Leo P, Reid Lee B, Kadlec Kelly, Fan Joline M, Allawala Anusha B, Racine Caroline A, Norbu Tenzin, Astudillo Dani, Tremblay-McGaw Alexandra G, Becker Natalie, Alhourani Ahmad, Starr Philip A, Chang Edward F, Krystal Andrew D
Weill Institute for Neurosciences, University of California, San Francisco.
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco.
medRxiv. 2025 Mar 17:2025.03.14.25323348. doi: 10.1101/2025.03.14.25323348.
Deep brain stimulation has been used to treat severe, refractory obsessive-compulsive disorder (OCD) with variable outcomes across multiple anatomical targets. To overcome these limitations, we developed an invasive brain mapping paradigm in which electrodes were implanted across the OCD cortico-striato-thalamo-cortical circuit in a single individual. We then performed extensive stimulation mapping during a multi-day inpatient stay to identify personalized therapeutic targets and characterize their downstream circuit effects. We found two targets within the right ventral capsule (VC) that acutely reduced OCD symptoms. Prolonged VC stimulation suppressed high frequency activity within the structurally and functionally connected orbitofrontal cortex, which encoded the severity of OCD symptoms. These VC sites were implanted for DBS and combined stimulation of these targets led to a rapid therapeutic response. This case provides the first proof-of-concept that invasive brain mapping can be used to guide a novel personalized, multi-site neuromodulation approach to treat refractory OCD.
深部脑刺激已被用于治疗严重的、难治性强迫症(OCD),在多个解剖靶点上的治疗效果各不相同。为了克服这些局限性,我们开发了一种侵入性脑图谱范式,在一个个体的强迫症皮质-纹状体-丘脑-皮质回路中植入电极。然后,在多天的住院期间进行了广泛的刺激图谱绘制,以确定个性化的治疗靶点,并表征其下游回路效应。我们在右侧腹侧囊(VC)内发现了两个靶点,它们能迅速减轻强迫症症状。长期的VC刺激抑制了结构和功能上相连的眶额皮质内的高频活动,而眶额皮质编码了强迫症症状的严重程度。将这些VC部位植入用于深部脑刺激,联合刺激这些靶点可导致快速的治疗反应。该病例提供了首个概念验证,即侵入性脑图谱可用于指导一种新型的个性化、多部位神经调节方法来治疗难治性强迫症。