LAUSR

Dear Editor, We are grateful toDr. Kim for his insightful comments on our paper entitled “Lack of association between dopamine transporter loss and non-motor symptoms in patients with Parkinson’s disease: a detailed PET analysis of 12 striatal subregions” [1]. The important issue raised by Dr. Kim highlights an unknown relationship between anatomy-based segmentation and functional division of striatum. We agree that cortico-striatopallido-thalamo-cortical circuits including sensorimotor, associative, and limbic loop might be crucially implicated in the pathogenesis of non-motor symptoms in Parkinson’s disease (PD). To our knowledge, it has been widely accepted that the ventral striatum is connected to the limbic loop, the dorsomedial striatum (caudate nucleus) is linked with the associative loop, and the dorsolateral striatum (putamen) is related to the sensorimotor striatum, respectively [2]. Furthermore, we divided such segmentation of the striatum into 12 subregions more specifically, according to the literatures; such subregional analysis including anterior-posteriorventral divisions of the putamen was highly associated with the functional connectivity of the striatum [3–5]. Taken together, we supposed that such anatomical subregions of the striatum in our study could considerably represent the functional circuits of the striatum. Moreover, considering variable functional clusters of the striatum, we deduced that more specific subdivision may provide more accurate relationship with the pathophysiology of various non-motor symptoms in PD, since diverse non-motor symptoms might be interconnected. That is the reason why the 12 subregions of striatum were utilized in the association with non-motor symptoms of PD in our study. Besides, functional circuits of the striatum consist of not only dopaminergic neurons but also non-dopaminergic neurons including glutamatergic or GABAergic neurons. We just focused on the contribution of dopaminergic pathway in relationship with non-motor symptoms of PD. Therefore, unlike Dr. Kim’s opinion, our conclusion was not that the dopaminergic pathway might not be associated with NMS of PD. Instead, we concluded that the non-dopaminergic pathways may play more important roles in non-motor symptoms of PD, compared to the dopaminergic pathway. Finally, we agree with Dr. Kim that we enrolled patients in relatively early stages of PD. Moreover, as described in the shortcomings, our study has several limitations inferring that the interpretation of the results should be cautious. However, through this PET analysis of 12 striatal subregions, we could more accurately investigate the association between anatomy-based functional subdivision of the striatum and various non-motor symptoms of PD. We believe that our study provides one meaningful finding in this exciting field to move forward, and should be confirmed by other groups to obtain a consistent view for the pathogenesis of non-motor symptoms in PD.