IntroductionChronic pain (CP) disproportionately affects older adults, not only because it is more prevalent in later life, but also because it may exacerbate cognitive aging and is associated with increased dementia risk [1]. Recent research has implicated accelerated brain aging in CP patients as a potential mechanism behind their disrupted cognitive aging [1]. However, this work remains limited in its focus on structural features of brain aging in CP. Alternatively, the role of functional brain network segregation in normative neurocognitive aging has been robustly characterized; it declines with age, with lower segregation linked to cognitive decline and dementia risk [2,3]. Whether CP disrupts these relationships has not yet been examined.
MethodsParticipants included healthy controls without ongoing pain, and CP patients with chronic back pain or fibromyalgia. After age-sex matching and censoring participants with fMRI head motion above acceptable values, the final sample included 60 controls and 141 CP patients. Executive cognition was assessed using the n-back task, stop-signal task, and Stroop task. Functional brain network segregation was quantified using the system segregation metric, with network communities defined using the Harvard-Oxford Optimized parcellation. PROCESS moderation analysis in SPSS was used to test interaction effects.
ResultsOverall system segregation and cognition did not differ between healthy controls and CP patients. However, older age predicted poorer performance across all tasks in the patient group, but only stop-signal performance in controls, with diagnosis significantly moderating the association between age and stroop task performance. Despite this accelerated cognitive aging pattern, system segregation declined with age in controls but not CP patients, with diagnosis also moderating this association. Finally, CP diagnosis significantly reversed the association between working memory (n-back accuracy) and system segregation: higher segregation predicted better working memory in controls but worse working memory in CP patients.
DiscussionWe found that chronic pain was associated with an altered brain aging trajectory in which network segregation is relatively preserved but becomes cognitively maladaptive, predicting worse rather than better working memory performance. If age-related declines in segregation reflect compensation for structural degeneration, this pattern may indicate impaired functional compensation in chronic pain patients, who already show accelerated structural brain aging [1]. Overall, our findings suggest that the role of system segregation in neurocognitive aging is disrupted in the presence of CP, with important implications for interpreting related neuroimaging biomarkers and developing cognitive interventions in this population [3].
References1: Zhao, L., Zhang, L., Tang, Y., & Tu, Y. (2025). Cognitive impairments in chronic pain: A brain aging framework. Trends in Cognitive Sciences.
https://doi.org/10.1016/j.tics.2024.12.004 2: Calder, C. N., Helmick, C., & Hashmi, J. A. (2026). High brain network system segregation is differentially linked with cognitive performance across the life span. Network Neuroscience, 10(2), 352–373.
https://doi.org/10.1162/NETN.a.5423: Zhang, Z., Chan, M. Y., Han, L., Carreno, C. A., Winter-Nelson, E., Wig, G. S., & Alzheimer’s Disease Neuroimaging Initiative. (2023). Dissociable effects of Alzheimer’s disease-related cognitive dysfunction and aging on functional brain network segregation. Journal of Neuroscience, 43(46), 7879–7892.
https://doi.org/10.1523/JNEUROSCI.0579-23.2023AcknowledgementI would like to thank my supervisor, Dr. Javeria Hashmi, and the entire Netphys lab for supporting this research and fostering a passionate environment for scientific thought.
My work was supported by the Brain Repair Centre through the Dalhousie Faculty of Medicine 2025 Graduate Studentship program and by the CIHR through the Canada Graduate Scholarship – Master’s Program.
