Abstract: A. Pentari, N. Simos, G. Tzagarakis, A. Kagialis, G. Bertsias, E. Kavroulakis, E. Gratsia, P. Sidiropoulos, D. TBoumpas, E. Papadaki (2023)

Objective To determine whole-brain and regional functional connectivity (FC) characteristics of patients with neuropsychiatric SLE (NPSLE) or without neuropsychiatric manifestations (non-NPSLE) and examine their association with cognitive performance.

Methods Cross-recurrence quantification analysis (CRQA) of resting-state functional MRI (rs-fMRI) data was performed in 44 patients with NPSLE, 20 patients without NPSLE and 35 healthy controls (HCs). Volumetric analysis of total brain and specific cortical and subcortical regions, where significant connectivity changes were identified, was performed. Cognitive status of patients with NPSLE was assessed by neuropsychological tests. Group comparisons on nodal FC, global network metrics and regional volumetrics were conducted, and associations with cognitive performance were estimated (at p<0.05 false discovery rate corrected).

Results FC in patients with NPSLE was characterised by increased modularity (mean (SD)=0.31 (0.06)) as compared with HCs (mean (SD)=0.27 (0.06); p=0.05), hypoconnectivity of the left (mean (SD)=0.06 (0.018)) and right hippocampi (mean (SD)=0.051 (0.0.16)), and of the right amygdala (mean (SD)=0.091 (0.039)), as compared with HCs (mean (SD)=0.075 (0.022), p=0.02; 0.065 (0.019), p=0.01; 0.14 (0.096), p=0.05, respectively). Hyperconnectivity of the left angular gyrus (NPSLE/HCs: mean (SD)=0.29 (0.26) and 0.10 (0.09); p=0.01), left (NPSLE/HCs: mean (SD)=0.16 (0.09) and 0.09 (0.05); p=0.01) and right superior parietal lobule (SPL) (NPSLE/HCs: mean (SD)=0.25 (0.19) and 0.13 (0.13), p=0.01) was noted in NPSLE versus HC groups. Among patients with NPSLE, verbal episodic memory scores were positively associated with connectivity (local efficiency) of the left hippocampus (r 2 =0.22, p=0.005) and negatively with local efficiency of the left angular gyrus (r 2 =0.24, p=0.003). Patients without NPSLE displayed hypoconnectivity of the right hippocampus (mean (SD)=0.056 (0.014)) and hyperconnectivity of the left angular gyrus (mean (SD)=0.25 (0.13)) and SPL (mean (SD)=0.17 (0.12)).

Conclusion By using dynamic CRQA of the rs-fMRI data, distorted FC was found globally, as well as in medial temporal and parietal brain regions in patients with SLE, that correlated significantly and adversely with memory capacity in NPSLE. These results highlight the value of dynamic approaches to assessing impaired brain network function in patients with lupus with and without neuropsychiatric symptoms.

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Altered hippocampal connectivity dynamics predicts memory performance in neuropsychiatric lupus: a resting-state fMRI study using cross-recurrence quantification analysis