How altered orbitofrontal signaling contributes to deficits in outcome-guided behavior in drug addiction

在世界范围内，物质使用障碍（SUD）患者和因药物过量而死亡的人数正在上升，导致卫生系统和社会的成本不断增加。因此，迫切需要更好地了解导致药物摄入和成瘾的过程。成瘾的特点是无法控制寻求药物的行为，尽管更好地了解消费的负面后果。这种未能充分参与结果导向行为可能与眶额叶信号传导缺陷有关。眼窝额叶皮层（OFC）参与承载“认知地图”，这是一种联想结构，使人们能够对尚未经历的结果进行心理模拟。该项目旨在研究眼窝额叶认知图在SUD患者中的功能。首先，在功能磁共振成像扫描期间，SUD患者将执行一项来自动物研究的感觉预处理任务，以深入了解他们在结果推断过程中潜在的行为和神经缺陷。随后，将通过经颅磁刺激（TMS）调节OFC活动，以影响相同任务中SUD患者的行为障碍。总之，这个项目将阐明眼窝额叶功能在药物成瘾中的作用。此外，这代表了现代刺激技术用于改变SUD患者决策缺陷的重要的第一步。

The numbers of patients with substance use disorder (SUD) and deaths from drug overdose are world-wide on the rise, resulting in growing costs for health systems and societies. Thus, there is an urgent need for a better understanding of the processes leading to drug intake and addiction. Addiction is characterized by an inability to control drug-seeking behavior despite better knowledge of the negative outcomes of consumption. This failure to adequately engage in outcome-guided behavior might be related to deficient orbitofrontal signaling. The orbitofrontal cortex (OFC) is involved in hosting a “cognitive map” which serves as an associative structure enabling mental simulations of yet unexperienced outcomes. The proposed project aims to investigate the functioning of orbitofrontal cognitive maps in SUD patients. First, a sensory preconditioning task adapted from animal research will be performed by SUD patients during fMRI scanning to provide insight into their potential behavioral and neural deficits during outcome inference. Subsequently, OFC activity will be modulated with transcranial magnetic stimulation (TMS) to influence the behavioral impairments of patients with SUD in the same task. In summary, this project will shed light on the involvement of orbitofrontal functioning in drug addiction. In addition, this represents an important first step towards the potential use of modern stimulation techniques to alter deficient decision making in SUD patients.