Movement Disorders Unit, Neurological Institute, Tel-Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel-Aviv, Israel.
Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
Brain Imaging Behav. 2019 Aug;13(4):1009-1020. doi: 10.1007/s11682-018-9920-2.
Disturbances in reward processing occur in Parkinson's disease (PD) however it is unclear whether these are solely drug-related. We applied an event-related fMRI gambling task to a group of non-manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene, in order to assess the reward network in an "at risk" population for future development of PD. Sixty-eight non-manifesting participants, 32 of which were non-manifesting non-carriers (NMNC), performed a gambling task which included defined intervals of anticipation and response to both reward and punishment in an fMRI setup. Behavior and cerebral activations were measured using both hypothesis driven and whole brain analysis. NMC demonstrated higher trait anxiety scores (p = 0.04) compared to NMNC. Lower activations were detected among NMC during risky anticipation in the left nucleus accumbens (NAcc) (p = 0.05) and during response to punishment in the right insula (p = 0.02), with higher activations among NMC during safe anticipation in the right insula (p = 0.02). Psycho-Physiological Interaction (PPI) analysis from the NAcc and insula revealed differential connectivity patterns. Whole brain analysis demonstrated divergent between-group activations in distributed cortical regions, bilateral caudate, left midbrain, when participants were required to press the response button upon making their next chosen move. Abnormal neural activity in both the reward and motor networks were detected in NMC indicating involvement of the ventral striatum regardless of medication use in "at risk" individuals for future development of PD.
奖赏处理障碍在帕金森病（PD）中很常见，但尚不清楚这些障碍是否仅与药物有关。我们应用事件相关 fMRI 赌博任务对 LRRK2 基因 G2019S 突变的非显性携带者（NMC）进行了研究，以评估处于未来 PD 发展“风险”的人群的奖赏网络。我们招募了 68 名非显性参与者，其中 32 名是非显性非携带者（NMNC），他们在 fMRI 环境中完成了包括奖赏和惩罚预期和反应的明确间隔的赌博任务。使用假设驱动和全脑分析测量了行为和大脑激活。NMC 的特质焦虑评分明显更高（p=0.04）。与 NMNC 相比，NMC 在左侧伏隔核（NAcc）的风险预期期间（p=0.05）和对惩罚的反应期间（p=0.02）的激活程度较低，在右侧岛叶的安全预期期间（p=0.02）的激活程度较高。来自 NAcc 和岛叶的心理生理交互（PPI）分析显示出不同的连接模式。全脑分析显示，当参与者需要在做出下一个选择动作时按下响应按钮时，分布在皮质区域、双侧尾状核、左侧中脑的两组之间存在差异。NMC 中检测到奖赏和运动网络的异常神经活动，表明即使在“风险”个体中使用药物，腹侧纹状体也可能参与其中，这与未来 PD 的发展有关。
