Objective: To spatially localize disruptions in default mode network connectivity in prodromal and diagnosed Parkinson’s disease relative to controls.

Background: Previously our research team reported reductions in global signal between the eyes-open/eyes-closed state in Parkinson’s disease (PD) and REM sleep behavior disorder (RBD) patients relative to controls using resting-state fMRI [1].  We hypothesize these differences to be spatially localized to connectivity of the default mode network (DMN).

Method: 40 patients with PD, 37 with RBD, and 21 controls (CON) underwent 3T MRI including separate runs of eyes-open and eyes-closed resting state-fMRI. 20 PD, 15 RBD, and 8 CON returned a year later for a second session of imaging. Imaging data were preprocessed using fMRIPrep [2] followed by the Conn (v20b) pipeline for functional connectivity analysis [3] to isolate differences in DMN connectivity among groups using the seed-to-voxel approach with seed in anterior DMN (medial prefrontal cortex, MPFC, x,y,z=+1,+55, -3).

Results: We found a cluster of 483 (size p-FWE p=0.001) voxels centered in right intracalcarine cortex (-4, -50, 0) that differed significantly (F_(2,97)=12.89, p-FDR=0.00002) as a function of group and eye condition. Connectivity was positive in CON during eyes-closed and negative during eyes-open in both session 1 and session 2. PD and RBD failed to show this modulation in both imaging sessions, with negative connectivity in both eyes-open and eyes-closed conditions.

Conclusion: CON showed increased connectivity in the eyes-closed state between right occipital cortex and MPFC, with decreased connectivity during the eyes-open condition. Failure to modulate MPFC-occipital functional connectivity in PD and RBD was replicated in both imaging sessions, which can be interpreted as further evidence of disrupted DMN connectivity of visual impairment in PD [4], and should be explored as a confirmatory diagnostic tool and a prodromal biomarker given the similar pattern found between RBD and PD.

References: 1.Suescun, J., Schiess, M., Giancardo, L., Castriotta, R. and Ellmore, T., 2018, October. Diminished fMRI global signal differences between eyes closed and eyes open resting state in RBD and PD. In MOVEMENT DISORDERS (Vol. 33, pp. S659-S660). 2 .Esteban, O., Markiewicz, C.J., Blair, R.W., Moodie, C.A., Isik, A.I., Erramuzpe, A., Kent, J.D., Goncalves, M., DuPre, E., Snyder, M. and Oya, H., 2019. fMRIPrep: a robust preprocessing pipeline for functional MRI. Nature methods, 16(1), pp.111-116. 3.Whitfield-Gabrieli, S. and Nieto-Castanon, A., 2012. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain connectivity, 2(3), pp.125-141. 4.Lucas-Jiménez, O., Ojeda, N., Peña, J., Díez-Cirarda, M., Cabrera-Zubizarreta, A., Gómez-Esteban, J.C., Gómez-Beldarrain, M.Á. and Ibarretxe-Bilbao, N., 2016. Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson’s disease. Parkinsonism & related disorders, 33, pp.58-64

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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-eyes-open-closed-manipulation-reveals-disrupted-default-mode-network-connectivity-in-parkinsons-disease-and-rem-sleep-behavior-disorder/