Resting-State Functional Connectivity Signatures of Apathy in Community-Living Older Adults

Abstract

Apathy predicts poor outcomes in older adults, and its underlying neural mechanism needs further investigation. We examined the association between symptoms of apathy and functional connectivity (FC) in older adults without stroke or dementia. Participants included 48 individuals (mean age = 70.90) living independently in the community, who underwent resting-state fMRI and completed the Apathy Evaluation Scale (AES). Seed-to-voxel analysis (cluster-level p-FDR <0.05, voxel threshold p < 0.001) tested the association between AES scores and the whole-brain FC of brain regions involved in reward- and salience-related processing. We found that AES scores were negatively associated with FC of the right insula cortex and right anterior temporal regions (124 voxels, t = −5.10) and FC of the left orbitofrontal cortex and anterior cingulate regions (160 voxels, t = −5.45), and were positively associated with FC of the left orbitofrontal cortex and left lateral prefrontal (282 voxels, t = 4.99) and anterior prefrontal (123 voxels, t = 4.52) regions. These findings suggest that apathy in older adults may reflect disruptions in neural connectivity involved in reward- and salience-related processing.

Macrostructural and Microstructural White Matter Alterations Are Associated with Apathy across the Clinical Alzheimer’s Disease Spectrum

“…Therefore, damage to these tracts may play a role in affecting decision-making and response selection processes that may contribute to a significant reduction in self-initiated goal-directed actions consistent with a state of apathy, as suggested by the model proposed by Guimaraes et al [ 27 ]. This finding is consistent with previous observations reporting functional alterations in fronto-parietal networks [ 34 , 35 , 36 ] that have been interpreted as signs of enhanced cortical inhibition.…”

“…Alterations observed in both the uncinate and inferior fronto-occipital fasciculi may also be consistent with a disruption to insular connections, since a previous study found a substantial overlap between these associative tracts and structural connections of three insular sub-regions [ 70 ]. The insula, in particular the left one, has been found to be more atrophic [ 32 ] and its functional connectivity with fronto-parietal circuits to be altered in apathetic patients with AD [ 35 ] and cognitively unimpaired older adults [ 36 ]. The insula is part of the salience network together with the ACC, an area considered to be particularly involved in motivation regulation [ 55 ].…”

“…In line with this model, resting-state functional alterations have been found primarily in the salience and fronto-parietal networks that have been reported to be less functionally segregated in patients with AD and apathy compared with non-apathetic patients [ 34 ]. In particular, the insular cortices appear to be less functionally connected and the dorsolateral PFC more connected with fronto-parietal regions in apathetic older adults both with [ 35 ] and without AD [ 36 ]. These findings seem to suggest that a combination of reduced salience processing and interoception, and increased fronto-parietal inhibition, consistent with the model by Guimaraes et al [ 27 ], may explain the emergence of apathetic symptoms.…”

Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults

“…We also showed that plasma NfL levels modulated patterns of FC between the insula and medial orbitofrontal cortex, two lightly myelinated cortical areas that appeared to be vulnerable to detrimental effects of aging (Bartzokis, 2011;Vidal-Piñeiro et al, 2016). Recent evidence has linked rs-FC patterns of insular cortex and orbitofrontal cortex to apathy (Jang et al, 2021), a multi-domain syndrome associated with poor outcomes and incident dementia in normal older adults (van Dalen et al, 2018), suggesting that impaired FC of these two regions may have unfavorable implications for aging. Tract tracing studies in primates have revealed that the anterior insula has prominent connections to the orbitofrontal cortex (Flynn et al, 1999), forming a functional unit that serves in the integration of complex autonomic, cognitive and emotional processes (Morel et al, 2013), all of them manifestly affected by aging (Salthouse, 2012).…”

Effectiveness of using reward strategies combined with transcranial direct current stimulation (RstDCS) on motivation in chronic stroke patients with upper limb disorders: study protocol for a randomized controlled trial

“…Six months after stroke, not only psychogenic apathy may be caused by psychological and social factors, but also organic secondary apathy may be caused by neurobiological changes 18 . The possible neural mechanism is the impairment of the brain network related to goal directed behavior (GDB) 19 , which includes the anterior Cingulate cortex (ACC) and the nucleus accumbens (NAcc) 8,20 . Another likely reason is that infarction may lead to functional disruption of the connective area after an acute stroke 21 .…”