Identification of specific neural circuit underlying the key cognitive deficit of remitted late-onset depression: A multi-modal MRI and machine learning study

Abstract

Neuropsychological impairment is a key feature of late-onset depression (LOD), with deficits observed across multiple cognitive domains. And this neuropsychological impairment can persist even after the remission of depressive symptoms. However, none of previous studies have explored the pattern of cognitive deficit in remitted LOD (rLOD), and investigated the specific neural circuit underlying the key cognitive deficit of LOD. 40 rLOD patients and 36 controls underwent comprehensive neuropsychological assessments and magnetic resonance imaging (MRI) scans. The influence of executive function or information processing speed deficit on other cognitive domains was first investigated. We then applied a multivariate machine learning technique known as relevance vector regression to evaluate the potential of multiple-modal MRI (i.e., integrating whole-brain grey-matter [GM] volume and white-matter [WM] tract features) for making accurate predictions about the key cognitive deficit for individual rLOD patient. We revealed that the information processing speed appears to represent a key cognitive deficit in rLOD. Further the machine learning model identified a wide range of GM regions and WM tracts that significantly contributed to the prediction of individual performance on information processing speed (r = 0.50, P < 0.001). The GM regions mainly located in the frontal-subcortical and limbic systems; and the WM tracts mainly located in the frontal-limbic pathway, including the anterior corona radiata, fornix, posterior cingulate bundle, and uncinate fasciculus. This present study provide strongly evidence supporting the concept of rLOD that the core aspect of the cognitive deficits (i.e., information processing speed) is associated with disruption of the frontal-subcortical-limbic pathway.