Greater Link Identified in NMOSD Between Time-Varying Functional Connectivity and Depressive Symptoms Than Static Connectivity

Maria A. Rocca, MD

As previous studies have linked the precuneus to cognition and depression, recently published findings suggest that neuropsychological features of patients with neuromyelitis optica spectrum disorder (NMOSD) are correlated with time-varying functional connectivity (TVC) of the region rather than static functional connectivity (SFC).¹

Investigators also found that different TVC abnormalities underlie depressive symptoms and cognitive impairment as more depressive symptoms were associated with increased TVC between the precuneus and temporal lobe, while worse cognitive performance mainly correlated with higher TVC between the precuneus and parietal lobe. Of note, patients with NMOSD had both TVC and SFC abnormalities in the resting state (RS) functional connectivity (FC) of precuneus, but the changes of TVC were more diffused and better explained neuropsychological features.

Senior investigator Maria A. Rocca, head, Neuroimaging of CNS White Matter Unit, Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, and colleagues analyzed 27 right-handed patients and 30 age-, sex- and education-matched right-handed healthy controls (HC) enrolled between February 2012 and August 2015. Patients with a history of drug or alcohol abuse, head trauma, other neurological/psychiatric conditions, a formal diagnosis of major depressive disorder, and any contraindication to MRI, were excluded from the trial.

On the same day of the MRI acquisition, patients underwent a neurological evaluation including the Expanded Disability Status Scale (EDSS) assessment and a neuropsychological examination. SFC of the precuneus was assessed by producing a mean map of FC across all sliding windows, while the standard deviation (SD) of the map across all windows was chosen as a measure of TVC.

READ MORE: Cognitive Impairments, Visual Memory Hindered in Neuromyelitis Optica Spectrum Disorder

Among the cohort, cognitive impairment was observed in 12 patients (44.4%) and depressive symptoms in 17 patients (63.0%). Compared with HC, patients with NMOSD demonstrated decreased SFC between the precuneus and the right middle temporal gyrus, bilateral putamen, and right cerebellum. Additionally, these patients showed a widespread decrease in the TVC between the precuneus and the frontal lobes, parietal lobe, temporal lobe, occipital lobes, and deep gray matter. Additionally, investigators also identified increased intraprecuneal TVC and increased TVC between the precuneus and the left middle temporal gyrus.

To investigate subclinical depressive symptoms, individuals were administered the Beck Depression Inventory II (BDI), which quantifies the intensity of depressive symptoms, with a score of at 10 or more corresponding to at least mild depressive symptoms. For abnormal SFC, there was no correlation between BDI scores; although, investigators observed a bilateral correlation between higher BDI scores and increased TVC.

Verbal learning (VL) was tested with the Selective Reminding Test and its subsections, visuospatial learning (VSL) was assessed with the 10/36 Spatial Recall Test and its delayed recall, attention/information processing speed were evaluated through the Symbol Digit Modalities Test and the Paced Auditory Serial Addition Test-2 and 3, and verbal fluency (VF) was examined with the phonemic and semantic fluency tests. On cognitive performance, higher VL index correlated with decreased SFC between the precuneus and the right cerebellar crus-1.

Findings also showed that increased TVC between the precuneus and the right postcentral gyrus was correlated with higher CI index, IPS index and VSL index. Additionally, decreased TVC between the precuneus and the left inferior occipital gyrus correlated with higher VL index.

"Future studies should include NMOSD patients with a secondary diagnosis of major depressive disorders since we expect that TVC abnormalities would be more evident than in our cohort and will clarify whether these functional abnormalities are specific of NMOSD or only the epiphenomenon of depression," Rocca et al concluded.

REFERENCE
1. Cacciaguerra L, Mistri D, Valsasina P, Martinelli V, Filippi M, Rocca MA. Time-varying connectivity of the precuneus and its association with cognition and depressive symptoms in neuromyelitis optica: a pilot MRI study. Mult Scler J. Published online July 7, 2022. doi:10.1177/13524585221107125