Poly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fundamental posttranslational modification (PTM). PARP catalytic domains transfer the ADP-ribose ...moiety from NAD
to amino acid residues of target proteins, leading to mono- or poly-ADP-ribosylation (MARylation or PARylation). This PTM regulates various key biological and pathological processes. In this review, we focus on the roles of the PARP family members in inflammation and host-pathogen interactions. Here we give an overview the current understanding of the mechanisms by which PARPs promote or suppress proinflammatory activation of macrophages, and various roles PARPs play in virus infections. We also demonstrate how innovative technologies, such as proteomics and systems biology, help to advance this research field and describe unanswered questions.
During the past two decades, mindfulness meditation has gone from being a fringe topic of scientific investigation to being an occasional replacement for psychotherapy, tool of corporate well-being, ...widely implemented educational practice, and “key to building more resilient soldiers.” Yet the mindfulness movement and empirical evidence supporting it have not gone without criticism. Misinformation and poor methodology associated with past studies of mindfulness may lead public consumers to be harmed, misled, and disappointed. Addressing such concerns, the present article discusses the difficulties of defining mindfulness, delineates the proper scope of research into mindfulness practices, and explicates crucial methodological issues for interpreting results from investigations of mindfulness. For doing so, the authors draw on their diverse areas of expertise to review the present state of mindfulness research, comprehensively summarizing what we do and do not know, while providing a prescriptive agenda for contemplative science, with a particular focus on assessment, mindfulness training, possible adverse effects, and intersection with brain imaging. Our goals are to inform interested scientists, the news media, and the public, to minimize harm, curb poor research practices, and staunch the flow of misinformation about the benefits, costs, and future prospects of mindfulness meditation.
•We conducted a randomized trial of meditation for mild cognitive impairment (MCI).•Meditation may increase functional connectivity in the default mode network in MCI.•Mediation may reduce ...hippocampal volume atrophy in MCI.•Meditation may have a positive impact on brain regions most related to dementia.•Further research with larger sample sizes and longer-follow-up are needed.
Those with high baseline stress levels are more likely to develop mild cognitive impairment (MCI) and Alzheimer's Disease (AD). While meditation may reduce stress and alter the hippocampus and default mode network (DMN), little is known about its impact in these populations. Our objective was to conduct a “proof of concept” trial to determine whether Mindfulness Based Stress Reduction (MBSR) would improve DMN connectivity and reduce hippocampal atrophy among adults with MCI. 14 adults with MCI were randomized to MBSR vs. usual care and underwent resting state fMRI at baseline and follow-up. Seed based functional connectivity was applied using posterior cingulate cortex as seed. Brain morphometry analyses were performed using FreeSurfer. The results showed that after the intervention, MBSR participants had increased functional connectivity between the posterior cingulate cortex and bilateral medial prefrontal cortex and left hippocampus compared to controls. In addition, MBSR participants had trends of less bilateral hippocampal volume atrophy than control participants. These preliminary results indicate that in adults with MCI, MBSR may have a positive impact on the regions of the brain most related to MCI and AD. Further research with larger sample sizes and longer-follow-up are needed to further investigate the results from this pilot study.
Enhancing body awareness has been described as a key element or a mechanism of action for therapeutic approaches often categorized as mind-body approaches, such as yoga, TaiChi, Body-Oriented ...Psychotherapy, Body Awareness Therapy, mindfulness based therapies/meditation, Feldenkrais, Alexander Method, Breath Therapy and others with reported benefits for a variety of health conditions. To better understand the conceptualization of body awareness in mind-body therapies, leading practitioners and teaching faculty of these approaches were invited as well as their patients to participate in focus groups. The qualitative analysis of these focus groups with representative practitioners of body awareness practices, and the perspectives of their patients, elucidated the common ground of their understanding of body awareness. For them body awareness is an inseparable aspect of embodied self awareness realized in action and interaction with the environment and world. It is the awareness of embodiment as an innate tendency of our organism for emergent self-organization and wholeness. The process that patients undergo in these therapies was seen as a progression towards greater unity between body and self, very similar to the conceptualization of embodiment as dialectic of body and self described by some philosophers as being experienced in distinct developmental levels.
Neurophenomenological studies seek to utilize first-person self-report to elucidate cognitive processes related to physiological data. Grounded theory offers an approach to the qualitative analysis ...of self-report, whereby theoretical constructs are derived from empirical data. Here we used grounded theory methodology (GTM) to assess how the first-person experience of meditation relates to neural activity in a core region of the default mode network-the posterior cingulate cortex (PCC). We analyzed first-person data consisting of meditators' accounts of their subjective experience during runs of a real time fMRI neurofeedback study of meditation, and third-person data consisting of corresponding feedback graphs of PCC activity during the same runs. We found that for meditators, the subjective experiences of "undistracted awareness" such as "concentration" and "observing sensory experience," and "effortless doing" such as "observing sensory experience," "not efforting," and "contentment," correspond with PCC deactivation. Further, the subjective experiences of "distracted awareness" such as "distraction" and "interpreting," and "controlling" such as "efforting" and "discontentment," correspond with PCC activation. Moreover, we derived several novel hypotheses about how specific qualities of cognitive processes during meditation relate to PCC activity, such as the difference between meditation and "trying to meditate." These findings offer novel insights into the relationship between meditation and mind wandering or self-related thinking and neural activity in the default mode network, driven by first-person reports.
Attention to internal bodily sensations is a core feature of mindfulness meditation. Previous studies have not detected differences in interoceptive accuracy between meditators and nonmeditators on ...heartbeat detection and perception tasks. We compared differences in respiratory interoceptive accuracy between meditators and nonmeditators in the ability to detect and discriminate respiratory resistive loads and sustain accurate perception of respiratory tidal volume during nondistracted and distracted conditions. Groups did not differ in overall performance on the detection and discrimination tasks; however, meditators were more accurate in discriminating the resistive load with the lowest ceiling effect. Meditators were also more accurate during the nondistracted tracking task at a lag time of 1 s following the breath. Results provide initial support for the notion that meditators have greater respiratory interoceptive accuracy compared to nonmeditators.
Cued spatial attention modulates functionally relevant alpha rhythms in visual cortices in humans. Here, we present evidence for analogous phenomena in primary somatosensory neocortex (SI). Using ...magnetoencephalography, we measured changes in the SI mu rhythm containing mu-alpha (7-14 Hz) and mu-beta (15-29 Hz) components. We found that cued attention impacted mu-alpha in the somatopically localized hand representation in SI, showing decreased power after attention was cued to the hand and increased power after attention was cued to the foot, with significant differences observed 500-1100 ms after cue. Mu-beta showed differences in a time window 800-850 ms after cue. The visual cue also drove an early evoked response beginning ∼70 ms after cue with distinct peaks modulated with cued attention. Distinct components of the tactile stimulus-evoked response were also modulated with cued attention. Analysis of a second dataset showed that, on a trial-by-trial basis, tactile detection probabilities decreased linearly with prestimulus mu-alpha and mu-beta power. These results support the growing consensus that cue-induced alpha modulation is a functionally relevant sensory gating mechanism deployed by attention. Further, while cued attention had a weaker effect on the allocation of mu-beta, oscillations in this band also predicted tactile detection.
Interoception can be broadly defined as the sense of signals originating within the body. As such, interoception is critical for our sense of embodiment, motivation, and well-being. And yet, despite ...its importance, interoception remains poorly understood within modern science. This paper reviews interdisciplinary perspectives on interoception, with the goal of presenting a unified perspective from diverse fields such as neuroscience, clinical practice, and contemplative studies. It is hoped that this integrative effort will advance our understanding of how interoception determines well-being, and identify the central challenges to such understanding. To this end, we introduce an expanded taxonomy of interoceptive processes, arguing that many of these processes can be understood through an emerging predictive coding model for mind-body integration. The model, which describes the tension between expected and felt body sensation, parallels contemplative theories, and implicates interoception in a variety of affective and psychosomatic disorders. We conclude that maladaptive construal of bodily sensations may lie at the heart of many contemporary maladies, and that contemplative practices may attenuate these interpretative biases, restoring a person's sense of presence and agency in the world.
Using a common set of mindfulness exercises, mindfulness based stress reduction (MBSR) and mindfulness based cognitive therapy (MBCT) have been shown to reduce distress in chronic pain and decrease ...risk of depression relapse. These standardized mindfulness (ST-Mindfulness) practices predominantly require attending to breath and body sensations. Here, we offer a novel view of ST-Mindfulness's somatic focus as a form of training for optimizing attentional modulation of 7-14 Hz alpha rhythms that play a key role in filtering inputs to primary sensory neocortex and organizing the flow of sensory information in the brain. In support of the framework, we describe our previous finding that ST-Mindfulness enhanced attentional regulation of alpha in primary somatosensory cortex (SI). The framework allows us to make several predictions. In chronic pain, we predict somatic attention in ST-Mindfulness "de-biases" alpha in SI, freeing up pain-focused attentional resources. In depression relapse, we predict ST-Mindfulness's somatic attention competes with internally focused rumination, as internally focused cognitive processes (including working memory) rely on alpha filtering of sensory input. Our computational model predicts ST-Mindfulness enhances top-down modulation of alpha by facilitating precise alterations in timing and efficacy of SI thalamocortical inputs. We conclude by considering how the framework aligns with Buddhist teachings that mindfulness starts with "mindfulness of the body." Translating this theory into neurophysiology, we hypothesize that with its somatic focus, mindfulness' top-down alpha rhythm modulation in SI enhances gain control which, in turn, sensitizes practitioners to better detect and regulate when the mind wanders from its somatic focus. This enhanced regulation of somatic mind-wandering may be an important early stage of mindfulness training that leads to enhanced cognitive regulation and metacognition.
To determine whether placebo responses can be explained by characteristics of the patient, the practitioner, or their interpersonal interaction.
We performed an analysis of videotape and psychometric ...data from a clinical trial of patients with irritable bowel syndrome who were treated with placebo acupuncture in either a warm empathic interaction (Augmented, n = 96), a neutral interaction (Limited, n = 97), or a waitlist control (Waitlist, n = 96). We examined the relationships between the placebo response and a) patient personality and demographics; b) treating practitioner; and c) the patient-practitioner interaction as captured on videotape and rated by the Psychotherapy Process Q-Set.
Patient extraversion, agreeableness, openness to experience, and female gender were associated with placebo response, but these effects held only in the augmented group. Regression analyses controlling for all other independent variables suggest that only extraversion is an independent predictor of placebo response. There were significant differences between practitioners in outcomes; this effect was twice as large as the effect attributable to treatment group assignment. Videotape analysis indicated that the augmented group fostered a treatment relationship similar to a prototype of an ideal healthcare interaction.
Personality and gender influenced the placebo response, but only in the warm, empathic, augmented group. This suggests that, to the degree a placebo effect is evoked by the patient-practitioner relationship, personality characteristics of the patient will be associated with the placebo response. In addition, practitioners differed markedly in effectiveness, despite standardized interactions. We propose that the quality of the patient-practitioner interaction accounts for the significant difference between the groups in placebo response.
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