Intrinsic network activity reflects the fluctuating experience of tonic pain.

Although we know sensation is continuous, research on long-lasting and continuously changing stimuli is scarce and the dynamic nature of ongoing cortical processing is largely neglected. In a longitudinal study, 38 participants across four sessions were asked to continuously rate the intensity of an applied tonic heat pain for 20 min. Using group-independent component analysis and dual regression, we extracted the subjects' time courses of intrinsic network activity. The relationship between the dynamic fluctuation of network activity with the varying time courses of three pain processing entities was computed: pain intensity, the direction of pain intensity changes, and temperature. We were able to dissociate the spatio-temporal patterns of objective (temperature) and subjective (pain intensity/changes of pain intensity) aspects of pain processing in the human brain. We found two somatosensory networks with distinct functions: one network that encodes the small fluctuations in temperature and consists mainly of bilateral primary somatosensory cortex (SI), and a second right-lateralized network that encodes the intensity of the subjective experience of pain consisting of SI, secondary somatosensory cortex, the posterior cingulate cortex, and the thalamus. We revealed the somatosensory dynamics that build up toward a current subjective percept of pain. The timing suggests a cascade of subsequent processing steps toward the current pain percept.

Patients with chronic pain exhibit individually unique cortical signatures of pain encoding.

Chronic pain is characterised by an ongoing and fluctuating intensity over time. Here, we investigated how the trajectory of the patients' endogenous pain is encoded in the brain. In repeated functional MRI (fMRI) sessions, 20 patients with chronic back pain and 20 patients with chronic migraine were asked to continuously rate the intensity of their endogenous pain. Linear mixed effects models were used to disentangle cortical processes related to pain intensity and to pain intensity changes. At group level, we found that the intensity of pain in patients with chronic back pain is encoded in the anterior insular cortex, the frontal operculum, and the pons; the change of pain in chronic back pain and chronic migraine patients is mainly encoded in the anterior insular cortex. At the individual level, we identified a more complex picture where each patient exhibited their own signature of endogenous pain encoding. The diversity of the individual cortical signatures of chronic pain encoding results bridge between clinical observations and neuroimaging; they add to the understanding of chronic pain as a complex and multifaceted disease.

Individually unique dynamics of cortical connectivity reflect the ongoing intensity of chronic pain.

ABSTRACT: Chronic pain diseases are characterised by an ongoing and fluctuating endogenous pain, yet it remains to be elucidated how this is reflected by the dynamics of ongoing functional cortical connections. In this study, we investigated the cortical encoding of 20 patients with chronic back pain and 20 chronic migraineurs in 4 repeated fMRI sessions. A brain parcellation approach subdivided the whole brain into 408 regions. Linear mixed-effects models were fitted for each pair of brain regions to explore the relationship between the dynamic cortical connectivity and the observed trajectory of the patients' ratings of fluctuating endogenous pain. Overall, we found that periods of high and increasing pain were predominantly related to low cortical connectivity. The change of pain intensity in chronic back pain was subserved by connections in left parietal opercular regions, right insular regions, as well as large parts of the parietal, cingular, and motor cortices. The change of pain intensity direction in chronic migraine was reflected by decreasing connectivity between the anterior insular cortex and orbitofrontal areas, as well as between the PCC and frontal and anterior cingulate cortex regions. Of interest, the group results were not mirrored by the individual patterns of pain-related connectivity, which rejects the idea of a common neuronal core problem for chronic pain diseases. The diversity of the individual cortical signatures of chronic pain encoding results adds to the understanding of chronic pain as a complex and multifaceted disease. The present findings support recent developments for more personalised medicine.

Intrinsic network activity reflects the ongoing experience of chronic pain.

Analyses of intrinsic network activity have been instrumental in revealing cortical processes that are altered in chronic pain patients. In a novel approach, we aimed to elucidate how intrinsic functional networks evolve in regard to the fluctuating intensity of the experience of chronic pain. In a longitudinal study with 156 fMRI sessions, 20 chronic back pain patients and 20 chronic migraine patients were asked to continuously rate the intensity of their endogenous pain. We investigated the relationship between the fluctuation of intrinsic network activity with the time course of subjective pain ratings. For chronic back pain, we found increased cortical network activity for the salience network and a local pontine network, as well as decreased network activity in the anterior and posterior default mode network for higher pain intensities. Higher pain intensities in chronic migraine were accompanied with lower activity in a prefrontal cortical network. By taking the perspective of the individual, we focused on the variability of the subjective perception of pain, which include phases of relatively low pain and phases of relatively high pain. The present design of the assessment of ongoing endogenous pain can be a powerful and promising tool to assess the signature of a patient's endogenous pain encoding.