Repeated pain induces adaptations of intrinsic brain activity to reflect past and predict future pain

Abstract

Recent neuroimaging studies have revealed a persistent architecture of intrinsic connectivity networks (ICNs) in the signal of functional magnetic resonance imaging (fMRI) of humans and other species. ICNs are characterized by coherent ongoing activity between distributed brain regions during rest, in the absence of externally oriented behavior. While these networks strongly reflect anatomical connections, the relevance of ICN activity for human behavior remains unclear. Here, we investigated whether intrinsic brain activity adapts to repeated pain and encodes an individual's experience. Healthy subjects received a short episode of heat pain on 11 consecutive days. Across this period, subjects either habituated or sensitized to the painful stimulation. This adaptation was reflected in plasticity of a sensorimotor ICN (SMN) comprising pain related brain regions: coherent intrinsic activity of the somatosensory cortex retrospectively mirrored pain perception; on day 11, intrinsic activity of the prefrontal cortex was additionally synchronized with the SMN and predicted whether an individual would experience more or less pain during upcoming stimulation. Other ICNs of the intrinsic architecture remained unchanged. Due to the ubiquitous occurrence of ICNs in several species, we suggest intrinsic brain activity as an integrative mechanism reflecting accumulated experiences.

Introduction

Traditionally, functional magnetic resonance imaging (fMRI) studies have investigated changes of brain activity in response to sensory, motor or cognitive tasks that subjects performed in the MR scanner. Only recently, colleagues have revealed networks of distributed brain regions that are characterized by coherent ongoing activity in subjects at rest, in the absence of any observable behavior (Biswal et al., 1995, Greicius et al., 2003, Laufs et al., 2003, Damoiseaux et al., 2006, Fox and Raichle, 2007). These resting-state or intrinsic connectivity networks (ICNs) strongly resemble previously described task-activation patterns (Smith et al., 2009). However, the relevance of ICNs for human behavior remains a controversial issue.

ICNs transcend levels of consciousness and consistently occur in humans, monkeys and rats (Lu et al., 2007, Vincent et al., 2007, Greicius et al., 2008, Larson-Prior et al., 2009, Biswal et al., 2010). The ubiquity and robustness of the intrinsic functional architecture strongly supports the notion of ICNs reflecting underlying structural connectivity (Fox and Raichle, 2007, Hagmann et al., 2008, Honey et al., 2009). But there have also been reports of immediate variations in the coherence of ICNs associated with task performance of humans (Fox et al., 2007, Seeley et al., 2007, Albert et al., 2009, Lewis et al., 2009). We therefore hypothesize that at least portions of ICN activity continuously adapt with ongoing experiences and that intrinsic brain activity reflects past and anticipates future experiences.

In this study, we focused on repeated pain experiences and their relation to ICN activity before and after pain. More concretely, we asked whether recurring pain modulates functional connectivity (FC) within pain-relevant ICNs in a way that reflects recent pain and enables the prediction of future pain experiences. FC is a measure to quantify the strength of covarying activity between distributed voxels or brain regions. We derived ICNs by applying Independent Component Analysis (ICA) to resting state fMRI (rs-fMRI) data. Acute pain is consistently associated with neuronal activity in a distinct network of subcortical and cortical brain regions (Apkarian et al., 2005, Tracey and Mantyh, 2007). Among these, somatosensory cortices (SSC) process sensory aspects of pain, while the ventromedial prefrontal cortex (vmPFC) has been associated with its modulation (Koyama et al., 2005, Seymour et al., 2005). Despite our knowledge about activating these brain regions by acute pain, less is known about their role in encoding past and future pain. Yet, understanding how the brain processes pain beyond an immediate experience might help to explain the development of chronic pain conditions.