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

药物使用障碍（SUD）患者和药物过量死亡人数在世界范围内不断增加，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吸毒和吸毒成瘾的过程。成瘾的特点是，尽管对消费的负面后果有更好的了解，但无法控制寻求毒品的行为。这种未能充分参与结果导向行为可能与眶额信号传导缺陷有关。眶额皮层（OFC）参与了一个“认知地图”，它作为一个联想结构，使尚未经历的结果的心理模拟。该项目旨在研究SUD患者眶额认知地图的功能。首先，从动物研究中改编的感觉预处理任务将由SUD患者在fMRI扫描期间进行，以提供对结果推断期间潜在的行为和神经缺陷的洞察。随后，将通过经颅磁刺激（TMS）调制OFC活动，以影响SUD患者在相同任务中的行为障碍。总之，这个项目将揭示参与眶额功能在药物成瘾。此外，这代表了向潜在使用现代刺激技术改变SUD患者决策缺陷迈出的重要的第一步。

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.