Altered functional connectivity of the primary motor cortex in tremor dominant and postural instability gait difficulty subtypes of early drug-naive Parkinson’s disease patients

Background: The primary motor cortex (M1) is an important hub in the motor circuitry of Parkinson's disease (PD), but the subregions' function and their correlation to tremor dominant (TD) and postural instability and gait disturbance (PIGD) with PD remain unclear. This study aimed to determine whether the functional connectivity (FC) of the M1 subregions varied between the PD and PIGD subtypes. Methods: We recruited 28 TD patients, 49 PIGD patients, and 42 healthy controls (HCs). M1 was divided into 12 regions of interest using the Human Brainnetome Atlas template to compare FC among these groups. Results: Compared with HCs, TD and PIGD patients exhibited increased FC between the left upper limb region (A4UL_L) and the right caudate nucleus (CAU)/left putamen (PUT), between the right A4UL (A4UL_R) and the left anterior cingulate and paracingulate gyri (ACG)/bilateral cerebellum4_5 (CRBL4_5)/left PUT/right CAU/left supramarginal gyrus/left middle frontal gyrus (MFG), as well as decreased connectivity between the A4UL_L and the left postcentral gyrus and the bilateral cuneus, and between the A4UL_R and the right inferior occipital gyrus. TD patients showed increased FC between the right caudal dorsolateral area 6 (A6CDL_R) and the left ACG/right MFG, between the A4UL_L and the right CRBL6/right middle frontal gyrus, orbital part/bilateral inferior frontal gyrus, and orbital part (ORBinf), and between the A4UL_R and the left ORBinf/right MFG/right insula (INS). PIGD patients displayed increased connectivity between the A4UL_L and the left CRBL4_5. Compared with PIGD patients, TD patients exhibited increased connectivity between the A6CDL_R and the left ACG/right MFG and between the A4UL_R and the left ACG/left ORBinf/right INS/right MFG. Furthermore, in TD and PIGD groups, the FC strength between the A6CDL_R and right MFG was negatively correlated with PIGD scores, while the FC strength between the A4UL_R and left ORBinf/right INS was positively correlated with TD scores and tremor scores. Conclusion: Our results demonstrated that early TD and PIGD patients share some common injury and compensatory mechanisms. TD patients occupied more resources in the MFG, ORBinf, INS, and ACG, which can be used as biomarkers to distinguish them from PIGD patients.