The Impact of Alzheimer’s Disease on the Resting State Functional Connectivity of Brain Regions Modulating Pain: A Cross Sectional Study

Article type: Research Article

Authors: Monroe, Todd B.^{a; b; c; d; *} | Beach, Paul A.^e | Bruehl, Stephen P.^f | Dietrich, Mary S.^{a; f} | Rogers, Baxter P.^b | Gore, John C.^b | Atalla, Sebastian W.^{a; b; c} | Cowan, Ronald L.^{c; f}

Affiliations: [a] School of Nursing, Vanderbilt University, Nashville, TN, USA | [b] Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA | [c] Psychiatric Neuroimaging Program, Vanderbilt University Medical Center, Nashville, TN, USA | [d] Department of Psychiatry and Behavioral Sciences, Vanderbilt University, Nashville, TN, USA | [e] Department of Neurology & Ophthalmology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA | [f] School of Medicine, Vanderbilt University, Nashville, TN, USA

Correspondence: [*] Correspondence to: Todd B. Monroe, 461 21st Ave South, Office 419-GH, Nashville, TN 37240, USA. Tel.: +1 615 322 1719; Fax: +1 615 322 7788; E-mail: [email protected].

Abstract: Background: It is currently unknown why people with Alzheimer’s disease (AD) receive less pain medication and report pain less frequently. Objective: The purpose of this study was to determine the impact of AD on thermal psychophysics and resting-state functional connectivity (RSFC) among sensory, affective, descending modulatory, and default mode structures. Methods: Controls (n = 23, 13 = female) and age-matched people with AD (n = 23, 13 = females) underwent psychophysical testing to rate perceptions of warmth, mild, and moderate pain and then completed resting-state fMRI. Between groups analysis in psychophysics and RSFC were conducted among pre-defined regions of interest implicated in sensory and affective dimensions of pain, descending pain modulation, and the default mode network. Results: People with AD displayed higher thermal thresholds for warmth and mild pain but similar moderate pain thresholds to controls. No between-group differences were found for unpleasantness at any percept. Relative to controls, people with AD demonstrated reduced RSFC between the right posterior insula and left anterior cingulate and also between right amygdala and right secondary somatosensory cortex. Moderate pain unpleasantness reports were associated with increased RSFC between right dorsolateral prefrontal cortex and left ACC in controls only. Conclusions: While AD had little effect on unpleasantness, people with AD had increased thermal thresholds, altered RSFC, and no association of psychophysics with RSFC in pain regions. Findings begin to elucidate that in people with AD, altered integration of pain sensation, affect, and descending modulation may, in part, contribute to decreased verbal pain reports and thus decreased analgesic administration.

Keywords: Acute pain, Alzheimer’s disease, brain mapping, dementia, experimental thermal pain, functional connectivity, neurobiology, neuroimaging, pain perception, pain threshold, psychophysics

DOI: 10.3233/JAD-161187

Journal: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 71-83, 2017