Background & Aims
Research shows that individuals with chronic pain tend to recall memories that are less temporally specific, involve more pain-related content, and greater negative emotionality. A recent longitudinal study found that adults who remembered personal pain-related experiences with less temporal specificity were at greater risk of reporting pain for up to 1-year after surgery (1). The hippocampus is central to processing autobiographical memory for personal events from a specific time and place. Abnormal intrinsic and extrinsic connectivity of the hippocampus (2), including reduced activation of the hippocampus (3) has been linked to chronic pain. While a link between pain and hippocampal functioning has been identified, the role of memory in this association has not been investigated. The aim of this study was to investigate whether certain types of details retrieved in memories for surgery are associated with alterations in hippocampal functioning.
Methods
38 youth (10-18 years) undergoing major surgery (e.g., spinal fusion or orthopedic procedures) were recruited at Alberta Children’s Hospital. Participants completed questionnaires assessing pain measures and psychosocial factors 7 days before, and 1 week, 1 month, and 4 months after surgery. They also completed a memory interview 3-4 weeks after surgery where they described memories for their experiences of the first day after surgery. Memory narratives were coded for episodic and semantic details using a standardized protocol (4) as well as for content including pain; surgical/medical; body; coping; anxiety and fear; meaning-making; and positive, negative, and neutral emotion details. Resting state fMRI was collected before and 4-6 months after surgery. fMRI data was preprocessed using AFNI and FSL (5,6). Nodal and modular network matrices to measure hippocampal efficiency were computed for left and right hippocampus using the GRETNA toolbox (7).
Results
Multiple linear regression analyses were conducted with autobiographical memory variables as predictors and postsurgical global efficiency measures as the dependent variable. Due to violation of normality, postsurgical betweenness centrality of the left hippocampus was square-root transformed. Presurgical fMRI variables, pain intensity before and in the first 2 weeks after surgery, age, and sex were included as covariates. The proportion of episodic negative emotion details 3-4 weeks after surgery was significantly associated with betweenness centrality of the left hippocampus at 4-6 months β=19.90, SE=8.53, t(28)=2.33, p=0.03. Other memory variables, sex, age, and pre- and post-surgical pain intensity were not associated with postsurgical betweenness centrality (p>0.05).
Conclusions
Betweenness centrality is a metric of all the shortest paths in a network that pass through a given node in the brain. These results suggest that youth undergoing surgery who have more episodic negative emotion details in their memories retrieved 3-4 weeks after surgery are more likely to exhibit greater information flow in the left hippocampus 4-6 months later. This aligns with recent findings showing greater regional global efficiency of the right hippocampus in youth with chronic headache pain compared to healthy controls (8). Moreover, studies of adults with migraine pain demonstrated that global networks that were more efficient and faster in information transfer (9). The hippocampus is integral for the ability to recall episodic memories, and more specifically, their associated emotionality (11–13). Increased functional connectivity is related to altered emotional processing in surgical patients with possible implications for pain chronification.
References
- Waisman A, Kleiman V, Slepian PM, Clarke H, Katz J. Autobiographical memory predicts postsurgical pain up to 12 months after major surgery. Pain. 2022 Dec 1;163(12):2438–45.
- Mutso AA, Petre B, Huang L, Baliki MN, Torbey S, Herrmann KM, et al. Reorganization of hippocampal functional connectivity with transition to chronic back pain. J Neurophysiol. 2014 Mar 1;111(5):1065–76.
- Ayoub LJ, Barnett A, Leboucher A, Golosky M, McAndrews MP, Seminowicz DA, et al. The medial temporal lobe in nociception: a meta-analytic and functional connectivity study. Pain. 2019 Jun;160(6):1245–60.
- Levine B, Svoboda E, Hay JF, Winocur G, Moscovitch M. Aging and autobiographical memory: dissociating episodic from semantic retrieval. Psychol Aging. 2002 Dec;17(4):677–89.
- Jenkinson M, Beckmann CF, Behrens TEJ, Woolrich MW, Smith SM. FSL. NeuroImage. 2012 Aug 15;62(2):782–90.
- Cox RW. AFNI: Software for Analysis and Visualization of Functional Magnetic Resonance Neuroimages. Computers and Biomedical Research. 1996 Jun 1;29(3):162–73.
- Wang J, Wang X, Xia M, Liao X, Evans A, He Y. GRETNA: a graph theoretical network analysis toolbox for imaging connectomics. Frontiers in Human Neuroscience [Internet]. 2015 [cited 2024 Jan 20];9. Available from: https://www.frontiersin.org/articles/10.3389/fnhum.2015.00386
- Cobos KL, Long X, Lebel C, Rasic N, Noel M, Miller JV. Increased hippocampal efficiency is associated with greater headache frequency in adolescents with chronic headache. Cereb Cortex Commun. 2023;4(3):tgad013.
- Dai L, Zheng Q, Chen X, Wang J, Peng Y, Hu C, et al. Altered brain structural topological properties and its correlations with clinical characteristics in episodic migraine without aura. Neuroradiology. 2021 Dec 1;63(12):2099–109.
- Denkova E, Botzung A, Scheiber C, Manning L. Implicit emotion during recollection of past events: a nonverbal fMRI study. Brain Res. 2006 Mar 17;1078(1):143–50.
- Fink GR, Markowitsch HJ, Reinkemeier M, Bruckbauer T, Kessler J, Heiss WD. Cerebral representation of one’s own past: neural networks involved in autobiographical memory. J Neurosci. 1996 Jul 1;16(13):4275–82.
- Vandekerckhove MMP, Markowitsch HJ, Mertens M, Woermann FG. Bi-hemispheric engagement in the retrieval of autobiographical episodes. Behav Neurol. 2005;16(4):203–10.
- Waisman A, Pavlova M, Noel M, Katz J. Painful reminders: Involvement of the autobiographical memory system in pediatric postsurgical pain and the transition to chronicity. Canadian Journal of Pain. 2022 Jun 15;6(2):121–41.
Presenting Author
Anna Waisman
Poster Authors
Anna Waisman
Master of arts
York University
Lead Author
Anna Waisman
York University
Lead Author
Karen Cobos
University of Calgary
Lead Author
Chenyue Zhang
York University
Lead Author
Xiangyu Long
University of Calgary
Lead Author
Maria Pavlova
University of Calgary
Lead Author
Catherine Lebel
University of Calgary
Lead Author
Joel Katz
PhD
York University
Lead Author
Melanie N. Noel
PhD
Alberta Children’s Hospital Research Institute, Calgary, Alberta, Canada
Lead Author
Jillian Miller
University of Calgary
Lead Author
Topics
- Pain Imaging