Interoceptive inference, emotion, and the embodied self

The concept of the brain as a prediction machine has enjoyed a resurgence in the context of the Bayesian brain and predictive coding approaches within cognitive science. To date, this perspective has been applied primarily to exteroceptive perception (e.g., vision, audition), and action. Here, I describe a predictive, inferential perspective on interoception: ‘interoceptive inference’ conceives of subjective feeling states (emotions) as arising from actively-inferred generative (predictive) models of the causes of interoceptive afferents. The model generalizes ‘appraisal’ theories that view emotions as emerging from cognitive evaluations of physiological changes, and it sheds new light on the neurocognitive mechanisms that underlie the experience of body ownership and conscious selfhood in health and in neuropsychiatric illness

Does age affect the relationship between pain and disability? : a descriptive study in individuals suffering from chronic low back pain

Abstract : Background: Previous studies have revealed a weak to moderate relationship between pain and disability in individuals suffering from low back pain (LBP). However, to our knowledge, no studies have evaluated if this relationship is different between young and older adults. Purpose: The objective of this descriptive, cross-sectional study, was to determine if the relationship between LBP intensity and physical disability is different between young and older adults. Methods: Pain intensity (measured with a visual analog scale) and physical disability scores (measured with the Oswestry Disability Index) were collected from the medical files of 164 patients with LBP. Separate Pearson correlation coefficients were calculated between these 2 variables for young (mean age 40 ± 6 years, n = 82) and older (62 ± 9 years, n = 82) individuals and a Fisher r-to-z transformation was used to test for group differences in the strength of the relationship. Linear regression analyses were also performed to determine if the slope of the association was different between the 2 groups. Results: There was a significant and positive association between pain intensity and disability for both young and older individuals. However, the correlation was stronger in the young group (r = 0.66; p < 0.01) compared to the older group (r = 0.44; p < 0.01) (Fisher Z = 2,03; p < 0.05). The linear regression model also revealed that the slope of the relationship was steeper in the young group (p < .05). Conclusion: Although both young and older individuals showed a significant association between pain intensity and disability, the relationship between these 2 variables was more tenuous in older individuals than in young patients. Future research is essential to identify the factors underlying this age-related difference

"First pain" in humans: convergent and specific forebrain responses

<p>Abstract</p> <p>Background</p> <p>Brief heat stimuli that excite nociceptors innervated by finely myelinated (Aδ) fibers evoke an initial, sharp, well-localized pain ("first pain") that is distinguishable from the delayed, less intense, more prolonged dull pain attributed to nociceptors innervated by unmyelinated (C) fibers ("second pain"). In the present study, we address the question of whether a brief, noxious heat stimulus that excites cutaneous Aδ fibers activates a distinct set of forebrain structures preferentially in addition to those with similar responses to converging input from C fibers. Heat stimuli at two temperatures were applied to the dorsum of the left hand of healthy volunteers in a functional brain imaging (fMRI) paradigm and responses analyzed in a set of volumes of interest (VOI).</p> <p>Results</p> <p>Brief 41°C stimuli were painless and evoked only C fiber responses, but 51°C stimuli were at pain threshold and preferentially evoked Aδ fiber responses. Most VOI responded to both intensities of stimulation. However, within volumes of interest, a contrast analysis and comparison of BOLD response latencies showed that the bilateral anterior insulae, the contralateral hippocampus, and the ipsilateral posterior insula were preferentially activated by painful heat stimulation that excited Aδ fibers.</p> <p>Conclusions</p> <p>These findings show that two sets of forebrain structures mediate the initial sharp pain evoked by brief cutaneous heat stimulation: those responding preferentially to the brief stimulation of Aδ heat nociceptors and those with similar responses to converging inputs from the painless stimulation of C fibers. Our results suggest a unique and specific physiological basis, at the forebrain level, for the "first pain" sensation that has long been attributed to Aδ fiber stimulation and support the concept that both specific and convergent mechanisms act concurrently to mediate pain.</p

Anticipation of thermal pain in diverticular disease

Background The relative importance of peripheral nerve injury or differences in central pain processing in painful diverticular disease (DD) is unclear. Functional MRI has demonstrated changes in the anticipation of pain in irritable bowel syndrome (IBS), in whom dysfunctional central pain pro-cessing predominates. This study aims to identify anticipatory changes in Symptomatic DD (SDD) compared to asymptomatic DD (ADD) and IBS patients. Methods Cued painful cutaneous thermal stimuli were delivered to the left hand and foot of ADD, SDD or IBS patient groups during functional MRI. Gastrointestinal symptoms and somatization, via the physiological heath question 12 (PHQ12-SS) were evaluated. The SDD group was divided into 2 based on a PHQ12-SS score of ≤6 (low somatization: LSDD) or ≥7 (high somatization: HSDD). Fixed effect group analysis of the ‘cued’ anticipatory phase was performed. Key Results 74 participants were recruited to the study. After exclusions for excessive movement and incom-plete study data, 14 participants per group (IBS, ADD, LSDD and HSDD) were analysed and compared. Within the right posterior insula (pINS), a key somatosensory pain processing area, greater deactivation was found in the ADD compared to the LSDD, IBS and HSDD groups. In emotion processing centres, such as the anterior and middle insula (aINS and mINS), greater ac-tivation was identified in the LSDD, IBS and HSDD groups compared to the ADD group and in the LSDD compared to IBS and HSDD groups. Differences in left ACC activation were also seen between the LSDD and HSDD groups. In comparison the amygdala (AMYG) and/or hip-pocampal deactivation was greater in the ADD than the IBS and HSDD group and between the low and high somatising SDD groups. Altered descending nociceptive control centres also showed greater deactivation such as the medial frontal gyrus (which includes the dorsolateral prefrontal cortex, DLPFC) and orbito-frontal cortex in the ADD and the LSDD group compared to the HSDD and IBS groups. Conclusion & Inferences The high somatising SDD group have altered anticipatory responses to thermal pain, behaving similar to IBS group. The low somatising SDD are similar to ADD group. This suggests underly-ing differences in pain pathophysiology, and the need for individualized treatment strategies to target the cause of their chronic pain

Altered Regional Brain Morphology in Patients With Chronic Facial Pain

Persistent idiopathic facial pain (PIFP) is defined as a persistent, unilateral facial pain, not associated with sensory loss or other physical signs and with no obvious structural abnormalities that would sufficiently explain pain experience.We were interested whether there is evidence of altered brain morphology in patients with PIFP as it has been described in other chronic pain conditions.Using voxel-based morphometry we investigated regional gray matter volume in 11 PIFP patients and 11 age- and sex-matched healthy controls. Furthermore we calculated lateralization indices (LI) to investigate differences in interhemispheric gray matter asymmetries.We report a decrease in gray matter volume in the left anterior cingulate gyrus and left temporo-insular region, as well as in the left and right sensory-motor area, projecting to the representational area of the face. Analyses of LI values demonstrated an increased rightward asymmetry in the middle-anterior insular cortex in patients in comparison with healthy controls.Our data support previous findings showing that chronic pain states are display-altered brain morphology in brain regions know to be part of the pain system.( Headache 2010;50:1278-1285)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79282/1/j.1526-4610.2010.01637.x.pd

Disrupted Brain Circuitry for Pain‐Related Reward/Punishment in Fibromyalgia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102040/1/art38191.pd

Nociception-induced spatial and temporal plasticity of synaptic connection and function in the hippocampal formation of rats: a multi-electrode array recording

<p>Abstract</p> <p>Background</p> <p>Pain is known to be processed by a complex neural network (neuromatrix) in the brain. It is hypothesized that under pathological state, persistent or chronic pain can affect various higher brain functions through ascending pathways, leading to co-morbidities or mental disability of pain. However, so far the influences of pathological pain on the higher brain functions are less clear and this may hinder the advances in pain therapy. In the current study, we studied spatiotemporal plasticity of synaptic connection and function in the hippocampal formation (HF) in response to persistent nociception.</p> <p>Results</p> <p>On the hippocampal slices of rats which had suffered from persistent nociception for 2 h by receiving subcutaneous bee venom (BV) or formalin injection into one hand paw, multisite recordings were performed by an 8 × 8 multi-electrode array probe. The waveform of the field excitatory postsynaptic potential (fEPSP), induced by perforant path electrical stimulation and pharmacologically identified as being activity-dependent and mediated by ionotropic glutamate receptors, was consistently positive-going in the dentate gyrus (DG), while that in the CA1 was negative-going in shape in naïve and saline control groups. For the spatial characteristics of synaptic plasticity, BV- or formalin-induced persistent pain significantly increased the number of detectable fEPSP in both DG and CA1 area, implicating enlargement of the synaptic connection size by the injury or acute inflammation. Moreover, the input-output function of synaptic efficacy was shown to be distinctly enhanced by the injury with the stimulus-response curve being moved leftward compared to the control. For the temporal plasticity, long-term potentiation produced by theta burst stimulation (TBS) conditioning was also remarkably enhanced by pain. Moreover, it is strikingly noted that the shape of fEPSP waveform was drastically deformed or split by a TBS conditioning under the condition of persistent nociception, while that in naïve or saline control state was not affected. All these changes in synaptic connection and function, confirmed by the 2-dimentional current source density imaging, were found to be highly correlated with peripheral persistent nociception since pre-blockade of nociceptive impulses could eliminate all of them. Finally, the initial pharmacological investigation showed that AMPA/KA glutamate receptors might play more important roles in mediation of pain-associated spatiotemporal plasticity than NMDA receptors.</p> <p>Conclusion</p> <p>Peripheral persistent nociception produces great impact upon the higher brain structures that lead to not only temporal plasticity, but also spatial plasticity of synaptic connection and function in the HF. The spatial plasticity of synaptic activities is more complex than the temporal plasticity, comprising of enlargement of synaptic connection size at network level, deformed fEPSP at local circuit level and, increased synaptic efficacy at cellular level. In addition, the multi-synaptic model established in the present investigation may open a new avenue for future studies of pain-related brain dysfunctions at the higher level of the neuromatrix.</p

Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity

Objective Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. Methods Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. Results Patients with FM had greater connectivity within the DMN and right EAN (corrected P [ P corr ] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN ( P corr < 0.05). Conclusion These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77979/1/27497_ftp.pd

What Was I Thinking? Eye-Tracking Experiments Underscore the Bias that Architecture Exerts on Nuclear Grading in Prostate Cancer

We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here, we asked whether this bias is mediated by the non-conscious selection of nuclei that “match the expectation” induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists, each carcinoma was shown twice, once before a background of a low grade, tubule-rich carcinoma and once before the background of a high grade, solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists, nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger, darker, and more irregular nuclei when those were projected before kigh grade, solid carcinomas than before low grade, tubule-rich carcinomas (and vice versa). However, the morphometric differences of the selected nuclei accounted for only 11% of the architecture-induced bias, suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that “match the expectation”. In conclusion, selection of « matching nuclei » represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture