Brain Mechanisms Supporting the Modulation of Pain by Mindfulness Meditation

The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events. To better understand how meditation influences the sensory experience, we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After 4 d of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57% and pain intensity ratings by 40% when compared to rest. A two-factor repeated-measures ANOVA was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contralateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas. Together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information

Brain rhythms of pain

Pain is an integrative phenomenon that results from dynamic interactions between sensory and contextual (i.e., cognitive, emotional, and motivational) processes. In the brain the experience of pain is associated with neuronal oscillations and synchrony at different frequencies. However, an overarching framework for the significance of oscillations for pain remains lacking. Recent concepts relate oscillations at different frequencies to the routing of information flow in the brain and the signaling of predictions and prediction errors. The application of these concepts to pain promises insights into how flexible routing of information flow coordinates diverse processes that merge into the experience of pain. Such insights might have implications for the understanding and treatment of chronic pain

An Investigation into the Neurobiology of Treatment Response in patients with Major Depression: The Placebo Effect.

Recent trends in clinical neuroscience have moved toward identifying neurobiological predictors of antidepressant treatment effects in order to improve overall treatment efficacy in Major Depression, a pervasive and debilitating disorder in which complete remission occurs for only one-third of treatment-seeking patients. However, predictors of placebo effects have largely been overlooked. This is not a small concern: substantial placebo response rates have been documented within antidepressant clinical trials. Hence, neuroimaging predictors of placebo responses may elucidate the neural pathways responsible for depression recovery. Moreover, these predictors may identify patients with a greater susceptibility to placebo effects; in turn, informing patient stratification in antidepressant clinical trials to better distinguish between drug-specific and placebo effects or augment prescribed treatments for patients in clinical settings. This dissertation takes a network-based resting-state functional connectivity (rsFC) approach to investigate predictors of placebo and antidepressant responses with particular focus on the default-mode, salience, and executive networks. This approach allows for consistency with the inherent network organization of the brain and the network-based characterization of depression. Through this investigation, enhanced rsFC of the rostral anterior cingulate (rACC) within the salience network has emerged as a strong predictor of responses to placebo with antidepressant expectations. Furthermore, heightened rACC rsFC within the salience network manifests as a neurobiological pattern differentiating healthy subjects from depressed patients. Finally, in light of evidence that genetic variability within placebo-related pathways modulate placebo treatment outcomes in depression as well as analgesia, where neural and molecular bases of placebo have been extensively mapped, the final chapter of this dissertation observed an effect of genetic polymorphisms within the prepronociceptin gene, an endogenous opioid precursor neuropeptide associated with nociception and depression, on analgesic placebo-induced µ-opioid activation within the rACC and other well-established, placebo-related regions. This effect further corresponded with placebo-associated stress responses and anxiety. These findings enlighten our understanding of the neurobiology behind depression recovery through placebo effects and illustrate the importance of the rACC within antidepressant responses and healthy functioning. Finally, they contribute to a growing database of potential clinical neuroimaging and genetic markers of placebo responses which may substantially benefit therapeutic care in depression.PhDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116639/1/masikora_1.pd

The Neural and Psychological Constituents of Placebo and Distraction

Both placebo and distraction have long been used clinically to relieve pain. The present series of experiments examined the neural and cognitive processes that constitute these two psychological forms of analgesia. Study 1 provides evidence that overlapping cognitive resources are involved in both pain and executive attention and working memory. Study 2 provides evidence that these same executive attention and working memory resources are not involved in placebo analgesia, and that placebo analgesia and distraction provide separate routes to pain relief. Study 3 suggests that while distraction-based analgesia reduces the neural signature of pain, expectancy-driven placebo analgesia may not

Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report.

Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required

Expectancy and Treatment Interactions: A Dissociation between Acupuncture Analgesia and Expectancy Evoked Placebo Analgesia

Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects — including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) — interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture + high expectation and sham acupuncture + high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment).National Center for Complementary and Alternative Medicine (U.S.) (PO1-AT002048)National Center for Complementary and Alternative Medicine (U.S.) (R21AT00949

Pain: A Precision Signal for Reinforcement Learning and Control.

Since noxious stimulation usually leads to the perception of pain, pain has traditionally been considered sensory nociception. But its variability and sensitivity to a broad array of cognitive and motivational factors have meant it is commonly viewed as inherently imprecise and intangibly subjective. However, the core function of pain is motivational-to direct both short- and long-term behavior away from harm. Here, we illustrate that a reinforcement learning model of pain offers a mechanistic understanding of how the brain supports this, illustrating the underlying computational architecture of the pain system. Importantly, it explains why pain is tuned by multiple factors and necessarily supported by a distributed network of brain regions, recasting pain as a precise and objectifiable control signal

Cortico-brainstem mechanisms of biased perceptual decision-making in the context of pain

Perceptual decision-making is commonly studied using stimuli with different physical properties but of comparable affective value. Here, we investigate neural processes underlying human perceptual decisions in the affectively rich domain of pain using a drift-diffusion model in combination with a probabilistic cueing paradigm. This allowed us to characterize a novel role for the dorsolateral prefrontal cortex (DLPFC), whose anticipatory responses reflecting a decision bias were dependent on the affective value of the stimulus. During intense noxious stimulation, these model-based anticipatory DLPFC responses were linked to an engagement of the periaqueductal gray (PAG), a midbrain region implicated in defensive responses including analgesia. Complementing these findings on biased decision-making, the model parameter reflecting sensory processing predicted subcortical responses (in amygdala and PAG) when expectations were violated. Our findings highlight the importance of taking a broader perspective on perceptual decisions and link decisions about pain with subcortical circuitry implicated in endogenous pain modulation