Radically different
Nature Neuroscience, Published online: 26 June 2026; doi:10.1038/s41593-026-02331-y
Pascoli et al. show that nucleus accumbens dopamine transients evoked by reward-predictive cues encode subjective reward value in mice, predicting individual preference for drugs over natural rewards and forecasting vulnerability to compulsive drug-seeking behavior.
Background: Digital meditation-based interventions (MBIs) reach vast global audiences with millions of active users, yet concerns persist about the frequency and nature of adverse experiences (ie, AExs) occurring during meditation training. Some researchers have argued that AExs are substantially underdetected and reflect iatrogenic harm caused by meditation (ie, adverse effects [AEfs]). Others contend that these experiences largely reflect common stressors that would be experienced without meditation. These competing perspectives underscore the need for further research, particularly in the context of digital MBIs, the most widely used form of meditation training. Objective: This study examined the prevalence, predictors, and subjective evaluations of AExs during a digital MBI and tested whether reported experiences may be caused by meditation practice via comparisons between meditation-exposed and nonexposed participants. Methods: Data were drawn from 2 trials of the Healthy Minds Program. Exploratory study 1 (n=315) consisted of a sample of distressed US undergraduate students to estimate the prevalence of AExs and identify baseline predictors. Preregistered confirmatory study 2 (n=594) sampled distressed US adults from all 50 states to replicate findings from study 1 and to examine participants’ subjective evaluations of AExs. Study 2 additionally compared AEx rates between participants who did and did not complete guided meditations to assess whether AExs could be caused by meditation exposure. Study 3 (n=87) used qualitative methods to analyze study 1 participants’ responses to an open-ended question regarding their strategies for coping with AExs. Results: In studies 1 and 2, 27.9% (88/315) and 10.1% (40/396) of participants, respectively, reported at least one AEx during the study period, with 6.7% (21/315) and 3% (12/396) reporting functional impairment, largely aligning with previous research. Critically, in study 2, rates of AExs did not significantly differ between participants who did and did not complete guided meditations, suggesting that these experiences were not caused by meditation practice. Higher baseline depression, anxiety, loneliness, experiential avoidance, and perceived barriers to meditation predicted more frequent AExs. In studies 1 and 2, 89.8% (79/88) and 90% (36/40) of participants who reported AExs, respectively, indicated that they were glad to have learned to meditate. Qualitative analyses showed that participants used diverse coping strategies, often using skills learned through the Healthy Minds Program. Conclusions: AExs were relatively common but occurred at comparable rates among participants who did and did not meditate, challenging claims that such experiences were caused by meditation practice in distressed individuals. Although a small subset of participants reported some degree of functional impairment, most evaluated their AExs as tolerable and described their overall MBI experience as positive. Together, these findings highlight the importance of distinguishing AExs that likely reflect epiphenomena of preexisting distress or symptoms from iatrogenic harm attributable to MBIs. Trial Registration: Study 1: ClinicalTrials.gov NCT04741529; https://clinicaltrials.gov/study/NCT04741529; Study 2: ClinicalTrials.gov NCT06282523; https://clinicaltrials.gov/study/NCT06282523
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A next-generation device that detects signs of stress could have wide-ranging applications, from investigating sleep disorders to detecting signs of sepsis.
The polygraph detector, described in Science Advances, is worn on the chest and can even sense when a person is lying.
It allows psychophysiological states to be continuously monitored through a combination of multimodal sensing and wireless data transmission.
The gadget offers an alternative to current approaches such as such as polygraphy and polysomnography (PSG), which involve cumbersome wired sensors that limit their practicality.
“By uncovering mechanistic links between autonomic imbalance, stress reactivity, and health outcomes, these devices have the potential to transform diagnostic workflows, optimize educational programs, and enable personalized therapeutic monitoring across stress medicine, pediatrics, and behavioral health,” reported Sun Hong Kim, PhD, from the University of Seoul in South Korea, and co-workers.
Subtle physiological variations in cardiac, respiratory, electrodermal, and thermal activity often serve as indicators of compromised health or heightened stress responses.
These can be reflected in many scenarios, from pediatric sleep disorders that disrupt neurodevelopment to the psychological strain experienced in high-stakes clinical settings or during polygraph examinations.
Accurate monitoring of psychophysiological states is therefore essential for understanding how stress and autonomic dysfunction manifest across a wide spectrum of medical conditions.
However, most existing devices monitor only one or two parameters or rely on electrochemical sensors that detect sweat biomarkers, thereby failing to reflect the complex and dynamic interplay between multiple physiological systems.
Kim and co-workers therefore designed a single platform to enable comprehensive assessment of autonomic and stress-related physiology in real time.
The device continuously measures changes in heartbeat, skin temperature, and breathing, which are then converted using machine learning into measures of psychological strain.
The device had high fidelity with gold standard systems in quantifying the complex psychological stress induced by polygraph interviews and complex cognitive load tasks as well as the physical stress caused by repeatedly putting a hand in an iced water.
During overnight monitoring of children, it reliably identified arousals, hypopnea, and apnea while revealing disease-specific autonomic signatures among infants with Down syndrome.
Real-world deployment during emergency simulation training showed that multimodal stress signatures correlate inversely with performance, reflecting its value for medical education.
Machine learning analyses across all studies confirmed that multimodal features outperformed single-signal approaches in detecting stress and clinical events with high sensitivity and specificity.
“A particularly notable contribution lies in pediatric sleep medicine,” the authors noted.
“Simultaneous comparison with PSG confirms the ability to detect arousals, hypopnea, and apnea while also providing mechanistic insights into autonomic regulation.
“In infants with Down syndrome, multimodal analysis reveals attenuated sympathetic responsiveness and parasympathetic dominance, consistent with known vulnerabilities in airway patency and autonomic control.
“Such disease-specific autonomic signatures may serve as valuable biomarkers for risk stratification, early diagnosis, and targeted intervention in neurodevelopmental disorders.”
The post Wireless Stress Detector Offers Multiple Medical Uses appeared first on Inside Precision Medicine.
Interest in glucagon-like peptide 1 receptor agonists (GLP-1s) continues to surge due to their effectiveness in reducing body weight and improving metabolic outcomes. This includes interest in small molecule oral GLP-1s which are more bioavailable and more easily manufactured than their injectable counterparts.
Now data from a new study in mice performed by scientists at the University of Virginia shows that this emerging class of weight-loss drugs suppress hedonic eating by modulating a reward circuit deep in the brain that is separate from previously described mechanisms that broadly affect appetite. The scientists believe that this pathway could be an avenue by which GLP-1s treat other dysfunctions in reward processing such as substance use disorders.
Details of the National Institutes of Health-funded study were published this week in a Nature paper titled “A brain reward circuit inhibited by next-generation weight-loss drugs in mice.” In it, the team reported that they investigated the small-molecule GLP-1s including Eli Lilly’s recently approved drug orforglipron, also known by the brand name Foundayo, as well as danuglipron, an oral GLP-1 that was being developed by Pfizer until the company decided to discontinue its development in 2025.
Previous studies that explored the effects of larger peptide GLP-1s such as semaglutide in the brain have found that they suppress hunger-driven eating by engaging networks in the hypothalamus and hindbrain. What has been less clear is the mechanism by which small-molecule GLP-1s work. “As the accessibility of these medications continues to rise and patient uptake increases, it’s crucial that we understand the neural mechanisms underlying the effects we’re seeing,” said Lorenzo Leggio, MD, PhD, clinical director of NIH’s National Institute on Drug Abuse.
The current study gets scientists one step closer to that goal. According to the paper, the scientists first used gene editing to modify the GLP-1 receptors of mice to make them more humanlike. They then administered orforglipron or danuglipron to the mice, and identified brain regions where the drugs induced activity. The results showed that in addition to inducing activity in familiar pathways, the drugs also triggered the central amygdala, a region associated with desire that is deeper in the brain than scientists previously thought GLP-1s could directly reach. Further testing showed that once activated, the central amygdala reduced the release of dopamine into key hubs of the brain’s reward circuitry during hedonic feeding.
“We’ve known that GLP-1 drugs suppress feeding behavior driven by energy demand,” said co-corresponding author Ali Guler, PhD, a professor of biology at the University of Virginia. “Now it seems oral small-molecule GLP-1s also dial back eating for pleasure by engaging a brain reward circuit.”
Given the effect of these drugs on eating for pleasure, future studies could explore whether small-molecule GLP-1s can also suppress cravings for other addictive substances. It is a question that the team hopes to explore in follow up studies focused specifically on substance use disorder.
The post Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.