Resting state functional connectivity changes following mindfulness-based stress reduction predict improvements in disease control for patients with asthma.

BACKGROUND: The staggering morbidity associated with chronic inflammatory diseases can be reduced by psychological interventions, including Mindfulness-Based Stress Reduction (MBSR). Proposed mechanisms for MBSR's beneficial effects include changes in salience network function. Salience network perturbations are also associated with chronic inflammation, including airway inflammation in asthma, a chronic inflammatory disease affecting approximately 10% of the population. However, no studies have examined whether MBSR-related improvements in disease control are related to changes in salience network function. METHODS: Adults with asthma were randomized to 8 weeks of MBSR or a waitlist control group. Resting state functional connectivity was measured using fMRI before randomization, immediately post-intervention, and 4 months post-intervention. Using key salience network regions as seeds, we calculated group differences in change in functional connectivity over time and examined whether functional connectivity changes were associated with increased mindfulness, improved asthma control, and decreased inflammatory biomarkers. RESULTS: The MBSR group showed greater increases in functional connectivity between salience network regions relative to the waitlist group. Improvements in asthma control correlated with increased functional connectivity between the salience network and regions important for attention control and emotion regulation. Improvements in inflammatory biomarkers were related to decreased functional connectivity between the salience network and other networks. CONCLUSIONS: Increased resting salience network coherence and connectivity with networks that subserve attention and emotion regulation may contribute to the benefits of MBSR for patients with asthma. Understanding the neural underpinnings of MBSR-related benefits in patients is a critical step towards optimizing brain-targeted interventions for chronic inflammatory disease management.

Is placebo analgesia for heat pain a sensory effect? An exploratory study on minimizing the influence of response bias.

We explored the ongoing question of whether placebo analgesia alters afferent nociceptive processing in a novel paradigm designed to minimize the role of response bias in placebo measurement. First, healthy adult participants received a standard heat placebo induction and conditioning procedure using a topical "analgesic" cream applied to one arm. During a subsequent placebo testing procedure, participants rated stimuli on the placebo-treated arm and untreated arm, using a task that minimized subjects' ability to guess the expected response, thus reducing experimenter demand. Retrospectively participants reported moderate analgesia effectiveness (mean=5.3/10), but for individual temperature ratings, only 2 subjects exhibited a perceptual placebo response >5 points. Next, these subjects completed a novel, exploratory task designed to measure changes in inter-arm in discriminative accuracy that would be expected from changes in afferent nociception. Both placebo responders (but no non-responders) showed reduced discriminative ability when the hotter stimulus occurred on the placebo arm, an effect consistent with alterations in nociceptive afferent flow and unlikely to be caused by response bias.

Inhibitory rTMS of secondary somatosensory cortex reduces intensity but not pleasantness of gentle touch.

Research suggests that the discriminative and affective aspects of touch are processed differently in the brain. Primary somatosensory cortex is strongly implicated in touch discrimination, whereas insular and prefronal regions have been associated with pleasantness aspects of touch. However, the role of secondary somatosensory cortex (S2) is less clear. In the current study we used inhibitory repetitive transcranial magnetic stimulation (rTMS) to temporarily deactivate S2 and probe its role in touch perception. Nineteen healthy adults received two sessions of 1-Hz rTMS on separate days, one targeting right S2 and the other targeting the vertex (control). Before and after rTMS, subjects rated the intensity and pleasantness of slow and fast gentle brushing of the hand and performed a 2-point tactile discrimination task, followed by fMRI during additional brushing. rTMS to S2 (but not vertex) decreased intensity ratings of fast brushing, without altering touch pleasantness or spatial discrimination. MRI showed a reduced response to brushing in S2 (but not in S1 or insula) after S2 rTMS. Together, our results show that reducing touch-evoked activity in S2 decreases perceived touch intensity, suggesting a causal role of S2 in touch intensity perception.

The Role of PIEZO2 in Human Mechanosensation.

BACKGROUND: The senses of touch and proprioception evoke a range of perceptions and rely on the ability to detect and transduce mechanical force. The molecular and neural mechanisms underlying these sensory functions remain poorly defined. The stretch-gated ion channel PIEZO2 has been shown to be essential for aspects of mechanosensation in model organisms. METHODS: We performed whole-exome sequencing analysis in two patients who had unique neuromuscular and skeletal symptoms, including progressive scoliosis, that did not conform to standard diagnostic classification. In vitro and messenger RNA assays, functional brain imaging, and psychophysical and kinematic tests were used to establish the effect of the genetic variants on protein function and somatosensation. RESULTS: Each patient carried compound-inactivating variants in PIEZO2, and each had a selective loss of discriminative touch perception but nevertheless responded to specific types of gentle mechanical stimulation on hairy skin. The patients had profoundly decreased proprioception leading to ataxia and dysmetria that were markedly worse in the absence of visual cues. However, they had the ability to perform a range of tasks, such as walking, talking, and writing, that are considered to rely heavily on proprioception. CONCLUSIONS: Our results show that PIEZO2 is a determinant of mechanosensation in humans. (Funded by the National Institutes of Health Intramural Research Program.).

Encoding of Touch Intensity But Not Pleasantness in Human Primary Somatosensory Cortex.

UNLABELLED: Growing interest in affective touch has delineated a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, have cast doubt on the segregation of touch discrimination and affect, suggesting that S1 also encodes affective qualities. We used functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to examine the role of S1 in processing touch intensity and pleasantness. Twenty-six healthy human adults rated brushing on the hand during fMRI. Intensity ratings significantly predicted activation in S1, whereas pleasantness ratings predicted activation only in the anterior cingulate cortex. Nineteen subjects also received inhibitory rTMS over right hemisphere S1 and the vertex (control). After S1 rTMS, but not after vertex rTMS, sensory discrimination was reduced and subjects with reduced sensory discrimination rated touch as more intense. In contrast, rTMS did not alter ratings of touch pleasantness. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. SIGNIFICANCE STATEMENT: Growing interest in affective touch has identified a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, cast doubt on the separation of touch discrimination and affect. We used functional magnetic resonance imaging and repetitive transcranial magnetic stimulation to demonstrate the representation of touch discrimination and intensity in S1, but the representation of pleasantness in the anterior cingulate cortex, not S1. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. Our study contributes to growing delineation of the affective touch system, a crucial step in understanding its dysregulation in numerous clinical conditions such as autism, eating disorders, depression, and chronic pain.