Altered Cortical Gyrification, Functional Connections, and Underlying Neurotransmitter Information in Patients with Parkinson’s Disease with Levodopa-Induced Dyskinesia

The pathogenesis of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) remains uncertain. Our work sought to examine the cortical gyrification pattern and its corresponding functional connectivity alterations, along with the underlying neurotransmitter information, in LID of PD. We included 30 PD patients with LID (PD-LID group), 30 without LID (PD-NLID group), and 30 age- and gender-matched healthy controls (HC group). Regional cortical gyrification computed by local gyrification index (LGI) and seed-based resting-state functional connectivity (RSFC) were employed. We adopted the JuSpace toolset to further validate whether the spatial patterns in RSFC changes were linked with specific neurotransmitters. Compared to PD-NLID, PD-LID demonstrated lower regional LGI in the right inferior frontal gyrus (rIFG) (pars opercularis) and decreased RSFC between the rIFG and the left inferior parietal lobule (IPL). The decreased RSFC was correlated with the spatial distribution of the serotonin transporter (SERT) in the serotonergic system. In particular, the level of rIFG (pars opercularis) LGI was negatively related to the severity of LID and demonstrated good performance in detecting patients with PD-LID. Our main findings indicated that the hypogyrification of rIFG and its corresponding functional connectivity reduction with left IPL, as well as the underlying serotonergic neurotransmitter distribution, could underlie the neurobiological underpinnings of LID.