The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer.

The advent of neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), has significantly advanced our understanding of the neurophysiological processes supporting a wide spectrum of mind-body approaches to treat pain. A promising self-regulatory practice, mindfulness meditation, reliably alleviates experimentally induced and clinical pain. Yet, the neural mechanisms supporting mindfulness-based pain relief remain poorly characterized. The present review delineates evidence from a spectrum of fMRI studies showing that the neural mechanisms supporting mindfulness-induced pain attenuation differ across varying levels of meditative experience. After brief mindfulness-based mental training (ie, less than 10 hours of practice), mindfulness-based pain relief is associated with higher order (orbitofrontal cortex and rostral anterior cingulate cortex) regulation of low-level nociceptive neural targets (thalamus and primary somatosensory cortex), suggesting an engagement of unique, reappraisal mechanisms. By contrast, mindfulness-based pain relief after extensive training (greater than 1000 hours of practice) is associated with deactivation of prefrontal and greater activation of somatosensory cortical regions, demonstrating an ability to reduce appraisals of arising sensory events. We also describe recent findings showing that higher levels of dispositional mindfulness, in meditation-naïve individuals, are associated with lower pain and greater deactivation of the posterior cingulate cortex, a neural mechanism implicated in self-referential processes. A brief fMRI primer is presented describing appropriate steps and considerations to conduct studies combining mindfulness, pain, and fMRI. We postulate that the identification of the active analgesic neural substrates involved in mindfulness can be used to inform the development and optimization of behavioral therapies to specifically target pain, an important consideration for the ongoing opioid and chronic pain epidemic

Effects of Fear Conditioning on Pain : Moderation by Mindfulness and the HPA-axis

Un cercle vicieux par lequel la peur et la douleur se maintiennent explique le développement et maintient de troubles impliquant le conditionnement à la peur. Bien que les processus comportementaux et circuits neurobiologiques du conditionnement à la peur aient été étudiés extensivement, les effets de cet apprentissage sur la douleur sont peu connus. L’objectif de cette thèse était d’étudier les effets du conditionnement à la peur sur la neuro-psychophysiologie de la douleur chez des sujets sains, ainsi que les facteurs modérant ces effets. Les effets de l’apprentissage de la peur sur la douleur ont été examinés dans l’Étude 1 (N=47) lors d’une tâche de conditionnement classique Pavlovien. Les stimuli conditionnés étaient des images abstraites appariées à une stimulation électrique douloureuse lors de 50% des essais. Les rapports de douleur et réflexes nociceptif de flexion ont été acquis à chaque stimulation, et les réponses électrodermales ont été mesurées à chaque présentation d’image. Nous avons estimé deux paramètres régissant les réponses anticipatoires (électrodermales) de peur pour chaque essai au moyen d’une approche de modélisation computationnelle: les attentes face à l’occurrence d’une stimulation, et l’associabilité des images à la stimulation. Les résultats ont démontré que chacun des paramètres liés à la peur prédisait positivement la douleur ainsi que les réponses nociceptive spinales. Ces effets opéraient en partie directement sur les réponses supraspinales à la douleur, et en partie indirectement par une facilitation de l’influx nociceptif au niveau spinal. Les résultats ont également démontré que la médiation des effets de la peur sur la douleur par l’input nociceptif spinal était plus forte chez les individus rapportant davantage de ‘vigilance au danger’, et plus faibles chez ceux rapportant plus de détachement émotionnel. Dans l’Étude 2, nous avons examiné le rôle de l’expérience à long terme en méditation pleine conscience sur les effets de l’apprentissage de la peur sur la douleur. Onze méditants expérimentés ont été testés en utilisant le même protocole expérimental que celui de l’Étude 1. Comparés aux sujets contrôles de l’Étude 1 n’ayant pas d’expérience en méditation, le groupe de méditants a montré une réduction de la douleur rapportée en moyenne lors de la tâche de conditionnement, ainsi qu’une diminution des effets de la peur sur la douleur. Les méditants n’ont pas montré de modulation des processus de bas niveau défensifs ou des mécanismes d’apprentissage à la peur. Finalement, l’Étude 3 a examiné le rôle des différences inter-individuelles en réactivité de l’axe HPA, opérationnalisé par le niveau de cortisol sécrété pendant la tâche, sur les effets de la peur sur la douleur (N=23). Le protocole expérimental et d’analyses était similaire à celui des Études 1-2 avec l’inclusion d’un SC+ apparié à 100% avec le SI. Les individus ayant une plus grande réponse de cortisol pendant le conditionnement rapportaient en moyenne moins de douleur lors de la tâche, et présentaient une facilitation des réponses défensives spinales par le biais du conditionnement à la peur. Les résultats de cette thèse appuient le concept d’un cycle vicieux peur/douleur par des données neuropsychophysiologiques, et montrent que celui-ci est modéré par certains traits de personnalité, l’expérience à long-terme en méditation pleine conscience, et les différences individuelles en réactivité de l’axe HPA. Nos résultats appuient également le rôle bénéfique des techniques fondées sur l’acceptation et la pleine conscience pour briser le cycle peur-douleur et prévenir/traiter les manifestations pathologiques de l’exposition répétée à des évènements menaçants (ex: anxiété, douleur chronique).A vicious cycle through which fear and pain maintain each other explains the development and maintenance of disorders involving fear conditioning. While the behavioral processes and neurobiological circuits of fear conditioning have been extensively studied, the effects of fear learning on pain remain poorly understood. The objectives of this thesis were to examine the effects of fear conditioning on the neuropsychophysiology of pain, and the factors that could moderate these effects. The effects of fear learning on pain were examined in Study 1 in 47 human participants during a delay Pavlovian classical fear conditioning task. Conditioned stimuli were abstract visual cues that co-terminated with a painful electric shock on 50% of trials. Pain ratings and the spinal nociceptive flexion reflex were recorded in response to each US, and anticipatory skin conductance responses were recorded to each CS. A computational model of reinforcement learning was fitted to anticipatory SCRs and used to estimate fear learning parameters of expected shock probabilities and associability (uncertainty) to each CS+ paired. Both fear learning parameters positively predicted pain responses. These effects operated in part directly on pain ratings, and in part indirectly by facilitating ascending spinal nociceptive activity. The results also showed that the mediation of the effects of fear learning on pain by spinal nociception was enhanced for individuals reporting more trait harm vigilance, and decreased for individuals reporting more emotional detachment. In Study 2, we investigated the role of long term mindfulness meditation experience on the effects of fear learning on pain. Eleven experienced meditators (>1000 hours of experience) were tested using the same experimental and analysis protocol as in Study1, and were compared with the meditation-naïve participants from Study1. Compared to controls, experienced meditators showed an overall reduction in pain ratings during fear learning, as well as reduced effects of learning parameters on pain. No effects of fear learning on lower-level spinal or anticipatory learning responses were observed. Finally, Study 3 examined how individual differences in HPA axis reactivity, operationalized by the level of cortisol secreted during the task, affected pain modulation induced by fear-learning (N=23). A similar experimental and analysis protocol as in Studies 1-2 was used with an additional visual CS paired with the US on 100% of trials. Individuals with greater cortisol output during fear conditioning reported a global decrease in pain during the task, and showed a facilitation of defensive spinal responses via fear learning mechanisms. The results of this thesis support the notion of a vicious fear-pain cycle with neuropsychophysiological evidence, and show that this cycle is moderated by certain personality traits, meditation experience, and individual differences in HPA reactivity. Our results also highlight the role of techniques based on acceptation and mindfulness meditation to break the fear-pain cycle and prevent/treat pathological manifestations of repeated threat exposure (eg. anxiety, chronic pain)

Brief mindfulness training can mitigate the influence of prior expectations on pain perception

Background Recent neuroimaging evidence suggests that mindfulness practice may mitigate the biasing influence of prior cognitive and emotional expectations on pain perception. The current study tested this hypothesis using a pain-cueing paradigm, which has reliably been shown to elicit conditioned hypoalgesic and hyperalgesic effects. Specifically, we aimed to investigate whether the instructed use of a mindfulness compared to a suppression strategy differentially modulates the magnitudes of conditioned hypoalgesia and hyperalgesia. Methods Sixty-two healthy non-meditators were assigned to listen to either brief mindfulness or suppression instructions, in between the conditioning and testing phases of a pain-cueing task. Participants provided ratings of anticipatory anxiety, pain intensity and pain unpleasantness throughout the task. They also completed trait and state self-report measures of mindfulness and pain catastrophizing. Results Results indicated that the paradigm was successful in inducing conditioned hyperalgesic and hypoalgesic effects. Importantly, while we found evidence of cue-induced hyperalgesia in both groups, only the suppression group reported cue-induced hypoalgesia. No group differences in pain ratings were found for unconditioned (novel-cued) stimuli. Conclusions These findings provide partial support for recently proposed predictive processing models, which posit that mindfulness may lead to a prioritization of current sensory information over previous expectations. We explore potential explanations for the asymmetrical group differences in conditioned hypoalgesia versus conditioned hyperalgesia, and discuss our results in light of recent neuroimaging insights into the neuropsychological mechanisms of mindfulness and expectancy-driven pain modulation. Significance The current study provides novel insights into the working mechanisms of mindfulness-driven pain modulation. Our data suggest that brief mindfulness training may reduce the influence of prior beliefs and expectations on pain perception. This finding adds to growing evidence suggesting that mindfulness may alleviate pain via neuropsychological mechanisms opposite to those typically observed in conditioning/placebo procedures and other cognitive manipulations. These unique mechanisms underline the potential of mindfulness as an alternative to traditional cognitive pain regulatory strategies

Atypical Anxiety-Related Amygdala Reactivity and Functional Connectivity in Sant Mat Meditation

While meditation has drawn much attention in cognitive neuroscience, the neural mechanisms underlying its emotional processing remains elusive. Sant Mat meditators were recruited, who adopt a loving-kindness mode of meditation along with a vegetarian diet and an alcohol-restricted lifestyle and novices. We assessed their State-Trait Anxiety Inventory (STAI) and scanned their amygdala reactivity in response to an explicit and implicit (backward masked) perception of fearful and happy faces. In contrast with novices, meditators reported lower STAI scores. Meditators showed stronger amygdala reactivity to explicit happiness than to fear, whereas novices exhibited the opposite pattern. The amygdala reactivity was reduced in meditators regardless of implicit fear or happiness. Those who had more lifetime practice in meditation reported lower STAI and showed a weaker amygdala response to fear. Furthermore, the amygdala in meditators, relative to novices, had a stronger positive functional connectivity with the ventrolateral prefrontal cortex (PFC) to explicit happiness, but a more negative connectivity with the insula and medial orbitofrontal cortex (OFC) to explicit fear. Mediation analysis indicated the amygdala reactivity as the mediator for the linkage between meditation experience and trait anxiety. The findings demonstrate the neural correlates that underpin the beneficial effects of meditation in Sant Mat. Long-term meditation could be functionally coupled with the amygdala reactivity to explicit and implicit emotional processing, which would help reduce anxiety and potentially enhance well-being

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

A neurophenomenological approach to non-ordinary states of consciousness: hypnosis, meditation, and psychedelics

No contemporary unifying framework has been provided for the study of non-ordinary states of consciousness (NSCs) despite increased interest in hypnosis, meditation, and psychedelics. NSCs induce shifts in experiential contents (what appears to the experiencer) and/or structure (how it appears). This can allow the investigation of the plastic and dynamic nature of experience from a multiscale perspective that includes mind, brain, body, and context. We propose a neurophenomenological (NP) approach to the study of NSCs which highlights their role as catalysts of transformation in clinical practice by refining our understanding of the relationships between experiential (subjective) and neural dynamics. We outline the ethical implications of the NP approach for standard conceptions of health and pathology as well as the crucial role of experience-based know-how in NSC-related research and application. Keywords: agency; altered states of consciousness; hypnosis; meditation; psychedelics; sel

A neurophenomenological approach to non-ordinary states of consciousness: hypnosis, meditation, and psychedelics

No contemporary unifying framework has been provided for the study of non-ordinary states of consciousness (NSCs) despite increased interest in hypnosis, meditation, and psychedelics. NSCs induce shifts in experiential contents (what appears to the experiencer) and/or structure (how it appears). This can allow the investigation of the plastic and dynamic nature of experience from a multiscale perspective that includes mind, brain, body, and context. We propose a neurophenomenological (NP) approach to the study of NSCs which highlights their role as catalysts of transformation in clinical practice by refining our understanding of the relationships between experiential (subjective) and neural dynamics. We outline the ethical implications of the NP approach for standard conceptions of health and pathology as well as the crucial role of experience-based know-how in NSC-related research and application

Psychopathy to Altruism: Neurobiology of the Selfish–Selfless Spectrum

The age-old philosophical, biological, and social debate over the basic nature of humans as being “universally selfish” or “universally good” continues today highlighting sharply divergent views of natural social order. Here we analyze advances in biology, genetics and neuroscience increasing our understanding of the evolution, features and neurocircuitry of the human brain underlying behavior in the selfish–selfless spectrum. First, we examine evolutionary pressures for selection of altruistic traits in species with protracted periods of dependence on parents and communities for subsistence and acquisition of learned behaviors. Evidence supporting the concept that altruistic potential is a common feature in human populations is developed. To go into greater depth in assessing critical features of the social brain, the two extremes of selfish–selfless behavior, callous unemotional psychopaths and zealous altruists who take extreme measures to help others, are compared on behavioral traits, structural/functional neural features, and the relative contributions of genetic inheritance versus acquired cognitive learning to their mindsets. Evidence from population groups ranging from newborns, adopted children, incarcerated juveniles, twins and mindfulness meditators point to the important role of neuroplasticity and the dopaminergic reward systems in forming and reforming neural circuitry in response to personal experience and cultural influences in determining behavior in the selfish–selfless spectrum. The underlying neural circuitry differs between psychopaths and altruists with emotional processing being profoundly muted in psychopaths and significantly enhanced in altruists. But both groups are characterized by the reward system of the brain shaping behavior. Instead of rigid assignment of human nature as being “universally selfish” or “universally good,” both characterizations are partial truths based on the segments of the selfish–selfless spectrum being examined. In addition, individuals and populations can shift in the behavioral spectrum in response to cognitive therapy and social and cultural experience, and approaches such as mindfulness training for introspection and reward-activating compassion are entering the mainstream of clinical care for managing pain, depression, and stress

Functional neuroanatomy of meditation: A review and meta-analysis of 78 functional neuroimaging investigations

Meditation is a family of mental practices that encompasses a wide array of techniques employing distinctive mental strategies. We systematically reviewed 78 functional neuroimaging (fMRI and PET) studies of meditation, and used activation likelihood estimation to meta-analyze 257 peak foci from 31 experiments involving 527 participants. We found reliably dissociable patterns of brain activation and deactivation for four common styles of meditation (focused attention, mantra recitation, open monitoring, and compassion/loving-kindness), and suggestive differences for three others (visualization, sense-withdrawal, and non-dual awareness practices). Overall, dissociable activation patterns are congruent with the psychological and behavioral aims of each practice. Some brain areas are recruited consistently across multiple techniques - including insula, pre/supplementary motor cortices, dorsal anterior cingulate cortex, and frontopolar cortex - but convergence is the exception rather than the rule. A preliminary effect-size meta-analysis found medium effects for both activations (d = .59) and deactivations (d = -.74), suggesting potential practical significance. Our meta-analysis supports the neurophysiological dissociability of meditation practices, but also raises many methodological concerns and suggests avenues for future research