The impact of Alzheimer's disease on the functional connectivity between brain regions underlying pain perception

Patients with Alzheimer's disease (AD) are administered fewer analgesics and report less clinical pain compared with their cognitively-intact peers, prompting much speculation about the likely impact of neurodegeneration on pain perception and processing. This study used functional connectivity analysis to examine the impact of AD on the integrated functioning of brain regions mediating the sensory, emotional, and cognitive aspects of pain. Fourteen patients with AD and 15 controls attended two experimental sessions. In an initial psychophysical testing session, a random staircase procedure was used to assess sensitivity to noxious mechanical pressure applied to the thumbnail. In a subsequent brain imaging session, fMRI data were collected as participants received noxious or innocuous thumbnail pressure, delivered at intensities corresponding with previously identified subjective pain thresholds. Two approaches to functional connectivity analysis were utilised. A seed-based correlation method was first used to identify regions showing significant functional connectivity with the right dorsolateral prefrontal cortex (DLPFC). Functional connectivity between a network of 17 predefined pain processing regions was then assessed. Between-group comparisons revealed enhanced functional connectivity between the DLPFC and the anterior mid cingulate cortex, periaqueductal grey, thalamus, hypothalamus, and several motor areas in patients with AD compared with control group. Likewise, inter-regional functional connectivity across most regions of the predefined pain network was shown to be greater in the patient group, with the enhanced functional connectivity centred on three nodes: the DLPFC-R, hypothalamus, and PAG. The results of this study support previous research suggesting an interplay between pain and cognitive processes in patients with AD.