Utilizing Centromedian Thalamus Connectivity to Personalize Noninvasive Neuromodulation Targets

The centromedian nucleus (CM) of the thalamus is essential for arousal, attention, sensory processing, and motor control. Neuromodulation targeting CM dysfunction has shown efficacy in various neurological disorders. However, its individualized precise transcranial magnetic stimulation (TMS) remains unreported. Using resting-state functional MRI, we mapped CM-based functional connectivity (CM-FC) to develop a personalized TMS scheme for neurological conditions.

We first analyzed the CM-FC patterns of healthy subjects via 10 scanning sessions in three MRI scanners spanning two subject groups: one from the Human Connectome Project (n = 20, four sessions) dataset and the other from Hangzhou Normal University (n = 20, three sessions of 3 T MRI and three sessions of 1.5 T MRI). Pearson's correlation was used for CM-FC evaluation. Then, we proposed an overlapping index ranging from 1 to 10, and group-level clusters with the highest overlapping index located 4 cm beneath the scalp were identified. In the individual CM-FC map, watershed image segmentation was used to obtain an individual cluster. The peak voxel with the highest FC value within the individual cluster was defined as a potential individualized target for future TMS.

The spatial FC patterns were remarkably similar between the left and right CMs. CMs have widespread positive connectivity with cortical areas, including the sensorimotor cortex, supplementary motor area, middle frontal cortex, medial temporal cortex, and middle cingulate. Among the group-level FC patterns of the left and right CMs, only the left CM had a group cluster in the left primary sensorimotor cortex (PSMC, cluster size = 51) with an overlapping index of 10, that is, 10 sessions showed significant CM-FC.

The left PSMC exhibited reproducible FC with the left CM. The individual peak FC location in the left PSMC could be used as a TMS target for indirect modulation of CM activity and aid in the treatment of CM-related neurological disorders.