Introduction

In neuromyelitis optica spectrum disorders (NMOSD), cognitive impairment (CI) is considered as a unique relapse-unrelated manifestation of the disease [1]. Anti-aquaporin4 (AQP4)-IgG seems to inhibit neuronal plasticity and long-term potentiation. The precuneus (PCUN) is a hub region of the default-mode network (DMN), which is often altered in neurological disorders, in association with CI [2]. Correlations between DMN dynamic functional connectivity (dFC) and CI have been found in multiple sclerosis [3]; however, dFC analysis was never applied to NMOSD. Against this background, aim of this study was to explore the contribution of dFC of the PCUN at resting state (RS) to cognitive alterations in NMOSD.

Methods

3.0 T RS fMRI was acquired from 27 AQP4-positive NMOSD patients and 30 age- and sex-matched healthy controls (HC), undergoing a neuropsychological evaluation including global and domain-specific cognitive impairment indexes (CII) and Beck Depression Inventory II (BDI-II) scores. DFC of bilateral PCUN was assessed by means of seed-voxel correlation analysis on sliding windows of RS fMRI data (window length=22 repetition times, step=1 repetition time). Standard deviation of dFC across windows [4] was used as a measure of dynamicity (Figure 1). Age- and sex-adjusted between-group dFC comparisons and correlations with cognitive scores were assessed using SPM12 and full-factorial models.

Resuts

Compared to HC, NMOSD patients had reduced PCUN-dFC with caudate nucleus, superior temporal gyrus, rectus/olfactory bulb, middle/inferior occipital gyri, supplemental motor area, cerebellum and periacqueductal gray matter. An increased dFC in the PCUN and between PCUN and thalamus, putamen, middle temporal gyrus, rolandic operculum and parahippocampus was also observed (Figure 1). Sixty-three% of patients had depressive symptoms, with BDI-II score positively correlating with intra-PCUN-dFC and its connectivity with insula, rolandic operculum, middle temporal pole and several cerebellar regions. Forty-four% of patients had CI and information processing speed (IPS) was the most affected domain (59.2%). Global CII positively correlated with PCUN-dFC with hippocampus, amygdala and middle frontal gyrus.

Discussion

The PCUN is an associative cortex lying in the dorsal posteromedial parietal lobe, a strategic region between visual, sensory-motor, and limbic cortices. Such an anatomy contributes to its role in highly integrated cognitive tasks [5]. In our study, we found that abnormally high PCUN dFC with insular, temporal, frontal, limbic and cerebellar regions had detrimental effects on cognitive performances and depression in NMOSD. These findings suggest that the contribution of PCUN to cognition in NMOSD might be not solely based on its activation within large-scale networks such as the DMN, but also considering its time-varying connections with cortical associative/limbic areas and the infratentorial cerebellar projections, which might interfere with the cerebello-prefrontal circuits.

Conclusions

PCUN dFC supports the role of PCUN in cognitive performance in NMOSD. We observed a negative effect of higher dynamic connections with the temporal pole for cognition and with limbic and cerebellar regions for depressive symptoms.

Acknowledgements

No acknowledgement found.

References

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