The medial temporal lobe in nociception: a meta-analytic and functional connectivity study

Abstract

processing. Of importance, there has yet to be a formal investigation of the spatial consistency of MTL activations in healthy participants during experimental pain.In addition to studies in healthy participants, extant evidence indicates aberrant MTL activity in various chronic pain conditions [56,104,108]. Recent evidence in patients with back pain suggests that the transition from subacute to chronic pain may be mediated by MTL structures [134]. Specifically, reduced MTL resting state functional connectivity (rsFC) to other cortical regions [107] and smaller MTL volume [135] predict this transition. However, as with experimental pain, it is not clear which regions within the MTL are implicated in chronic pain and what their role may be.The overall aim of this study was to determine regions of the MTL consistently involved in nociceptive processing and pain modulation in health and disease. First, we sought to determine which regions of the MTL show consistent spatial activation in response to (1) experimental pain in healthy participants compared to baseline control conditions, and (2) chronic pain patients compared to healthy participants. To that end, we performed two coordinate-based meta-analyses of functional MRI (fMRI) studies of pain that indicated MTL engagement. We expected our first meta-analysis to show consistent MTL activation in the HC and PHG across studies reporting MTL activity. We expected our second metaanalysis to show consistent MTL activation in the HC across chronic pain neuroimaging studies. These analyses are the first formalized investigation of MTL functioning in nociceptive processing.To generate hypotheses about the mechanistic role of the HC in nociceptive processing from existing data, it is important to explore its network interactions. Thus, we aimed to determine the connectivity of those regions elucidated by our meta-analyses using data from four distinct cohorts of chronic low back pain patients (CBP). Given previous observations of abnormal MTL engagement in CBP, we predicted that CBP would show abnormal rsFC to regions involved in processing the affective dimension of pain, i.e., the anterior insula, midcingulate cortex, amygdala and medial prefrontal cortex [25,31,33,111,134]. METHODSOur ALE meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2015 guidelines and checklist [103]. Article selection criteriaOur article selection followed the PRISMA flow diagrams [102] as shown in Fig. 1. Studies were excluded based on any of the following nine criteria: (1) animal studies; (2) did not use standardized stereotactic (Montreal Neurological Institute (MNI) or Talairach) brain coordinates; (3) case reports; (4) diagnostic or surgical MRI; (5) structural imaging; (6) studies of acute medical pain conditions; (7) functional magnetic resonance imaging (fMRI) studies without a baseline control (for experimental pain studies) or control group (for chronic pain studies); (8) studies not written in the English language; and (9) studies ...

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