Higher-order sensorimotor circuit of the whole-brain functional network involved in pruritus regulation in atopic dermatitis.

Background: Little is known about the neural mechanisms underlying pruritus regulation in Atopic dermatitis (AD).

Objective: To investigate the functional changes of the resting-state whole brain network of AD participants and the mechanisms by which they were involved in pruritus regulation.

Method: Based on the functional magnetic resonance imaging data from 19 AD participants and 37 healthy controls (HC), a graph-theoretical measure of degree centrality (DC) conjoined with a voxel-level seed-based functional connectivity (FC) method was used to identify abnormal higher-order nodes and the functionally relevant circuit in AD participants compared to healthy controls (HC).

Results: Of 64 participants screened, 19 AD participants (12M/7F, median [IQR] age, 27 [14] years) and 36 HCs (13M/23F, median [IQR] age, 20 [1] years) were enrolled. DC values of the left superior frontal gyrus (LSFG) increased in AD participants and exhibited a negative correlation with the SCORAD score (r = -0.561, p = 0.012) compared with HC. In the FC analysis with LSFG as the seed, FC values of several sensory and motor regions increased in AD participants, highly overlapping with the anatomical distribution of the inferior fronto-occipital fascicle (IFOF). AD participants with severe pruritus exhibited lower levels of DC (T = -2.316, p = 0.033) and FC between the LSFG and left insula (T = -2.203, p = 0.042) than those with mild-to- moderate pruritus.

Conclusions And Relevance: LSFG was involved in pruritus regulation in AD by forming a high-order sensorimotor circuit through the IFOF, a white matter fascicle that proved to provide multimodal integration in motor control and sensory information processing. These results offer more mechanism-guided treatment targets for severe pruritus in AD.