The Precise Targeting Of Dorsolateral Subthalamic Nucleus And Its Reliability Of Functional Connectivity

Introduction Subthalamic nucleus（STN）is a key component of both the indirect and hyperdirect motor pathways of the basal ganglia,mediating inhibitory output from the basal ganglia to cortical motor areas.And higher functional connectivity between STN and motor cortex for Parkinson’s disease（PD）patients has been found in resting-state f MRI studies.Dorsolateral sensorimotor part of STN（DL-STN）is the most effective target during deep brain stimulation（DBS）surgery.Thus,both the precise localization on cortical surface via functional connectivity（FC）of DL-STN and its reliability in motor cortex are of great importance for the understanding of neuro-mechanism and treatment of PD.However,it has not been investigated yet.The current study focuses on the individualized target of DL-STN and the reliability of functional connectivity of DLSTN.Material and Methods Three Cohorts were included: Cohort-1,Cohort-2 and Cohort-3.Cohort-1:Twenty-one subjects（21.8 ± 1.8 years old,11 females）were scanned with BOLD RS-f MRI in three visits（V1,V2 and V3）for both eyes open（EO）and eyes closed（EC）states,with V1,V2 on a 3.0 T GE MR750 scanner,and V3 on a 3.0T Siemens Prisma scanner.Cohort-2:Eighty subjects（61.1±7.4 years old,51 females）were scanned with restingstate f MRI（RS-f MRI）Echo Planner Imaging（EPI）,and ESWAN on a 3.0 T GE MR750 scanner.Cohort-3:The data were part of the Consortium for Reliability and Reproducibility（Co RR）（http://fcon₁000.projects.nitrc.org/indi/Co RR/html/hnu₁.html）.Thirty healthy participants（24.4 ± 2.4 years old,15 females）who were scanned with RS-f MRI every three-day for one month,i.e.,there are 10 visits.As providing a stable and efficient target for the treatment of PD using f MRI-guided r TMS is our main aim in current study,too long interval time between treatments is not preferred,we just selected the first visit（V1）,the second visit（V2）,the third visit（V3）.On the other hand,the fifth visit（V5）（14 days after V1,IT=14D）was selected in the current study for the comparison between Cohort-1（V1 &V2,IT=14D）and Cohort-3.1)The intra-scanner and inter-scanner reliability of voxel-wise-whole-brain metrics（VWWB）were calculated in Cohort-1,providing the methodological basis for the reliability analysis in the following study.2)The individualized MNI DL-STN coordinates were defined on ESWAN images from Cohort-2,Then the Euclidean distance（ED）of both individual and average DL-STN coordinates was calculated.As the ED was less than 3 mm for the majority subjects,the average MNI DL-STN coordinate was defined as the representative of all the individual DL-STN coordinates,with left DL-STN coordinates:（-12,-16,-9）and right DL-STN coordinates:（13,-15,-9）.3)Then,functional connectivity of the left and right DL-STN were calculated and one-sample t-test was conducted for each visit on FC map,respectively.4)Further,the ICCs of FC of whole brain were performed.5)Finally,the ICCs of peak FC and peak FC coordinates within regions of interest（ROIs）were calculated.Results and Conclusions 1)For the intra-sanner reliability,Per AF ≈ ALFF > Re Ho > DC;for the inter-scanner reliability,Per AF > ALFF > Re Ho > DC.2)The differences of individual DL-STN coordinates were very small on the RSf MRI,so the average DL-STN coordinate was taken to apply to all subjects.It can be used in the future DL-STN f MRI studies.3)The significant functional connectivity between DL-STN and pre-SMA,pars trigularis,middle frontal gyrus（MFG）provided further evidence for the corticalbasal ganglia hyperdirect way.4)The left DL-STN showed moderate to high ICC of peak FC coordinate within middle frontal gyrus（BA9）both for Cohort-1 and Cohort-3.This result might provide a possible more efficient and stable target for the future treatment of PD with f MRI-guided TMS.