Sara W. Lazar

Major depressive disorder (MDD) is a heterogeneous mental disorder characterised by rumination. Mindfulness-based cognitive therapy (MBCT) is an evidence-based treatment developed to target rumination and recurrence risk. Ongoing studies have begun to identify neural changes associated with treatment effects. However, the low-dimensional organisation underlying whole-brain dynamics remains largely unexplored and may provide a more complete characterisation of the neural processes through which MBCT exerts its therapeutic effects in MDD. Here, we investigated functional magnetic resonance imaging (fMRI) of a randomised controlled trial of MBCT with treatment as usual (TAU), or TAU alone, in a group of MDD patients (N=80). We applied a novel framework, complex harmonics decomposition (CHARM), to uncover low-dimensional manifolds in the spacetime domain, capturing local as well as non-local interactions made possible by brain criticality and amplified by the anatomical long-range connectivity. We successfully identified distinct distributed spatiotemporal manifolds across brain states and outperformed traditional dimensionality reduction techniques. During rumination after MBCT we found consistent recruitment of regions involved in bodily and interoceptive processing integrated within the whole-brain across manifolds, changes in latent configurations associated with clinical and behavioural improvements, and greater flexibility within the reduced space. Integration of bodily and interoceptive processing regions within distributed whole-brain manifolds and greater brain flexibility may be associated with reduced 'stickiness' of ruminative thinking patterns following mindfulness training in depression. Our findings highlight the promise of low-dimensional manifolds and long-range interactions arising from critical brain dynamics in understanding how mindfulness targets depressive ruminative processing.

Breathing not only sustains life but also interacts with emotional states. Mounting evidence suggests that subtle variations in respiratory patterns—including their neural underpinnings—may serve as sensitive indicators of affective processes, yet the specific phases of spontaneous breathing have rarely been studied in detail. Here, we present a cross-sectional, exploratory investigation combining high-temporal-resolution respiratory measures, resting-state magnetoencephalography data, and psychological assessments in 46 healthy adults. Our analysis distinguishes three distinct phases—inspiration, expiration, and the brief but functionally significant post-expiratory pause (PEP). By correlating time-averaged Salience Network connectivity with aggregate respiratory metrics, we identify trait-level associations specific to the PEP in beta and gamma frequencies. Individuals with longer and more variable PEPs show distinct connectivity patterns associated with heightened depression and reduced life satisfaction. Connectivity patterns involving the right insula, bilateral anterior cingulate cortex, and left amygdala show robust correlations with these affective parameters, suggesting that this brief respiratory interval may serve as a window into interoceptive and emotional processing. Our findings highlight the overlooked role of the PEP in capturing meaningful interactions between respiration, neural circuits, and psychological well-being.

Ethical principles and societal regulations are critical to scientific integrity, but individual human factors greatly influence adherence to them. Personal virtues may play a significant role in reinforcing adherence to communal ethical scientific practices but remain largely unexplored. This paper examines how cultivating mindful ethical virtues through meditation could support scientific ethical principles . We propose that when practiced as skillful mental cultivation, meditation may help develop new personal virtues and strengthen or attune those already present—such as conscience, regard for consequence, harmlessness, or equanimity. These virtues conceptually align with scientific ethical principles like accountability, intellectual humility, social good, and objectivity, suggesting that meditation could help bridge a gap between external collective ethical frameworks and the internal personal motivations that drive scientific conduct. In this sense, meditation could be in service of promoting good science. We outline a framework mapping this conceptual alignment and propose contemplative scientists are key to advancing empirical investigation into this connection. To support this, we recommend developing and evaluating Mindfulness-Based Ethical Development Interventions (MBED). These programs could integrate secular ethical instruction with meditation practices, providing a non-sectarian approach to cultivating ethical behaviors relevant to the scientific community. We hope to generate discussion on the potential role of meditation in enhancing ethical scientific conduct, and the significance of personal virtues in driving scientific progress. By focusing on the intersection of personal virtues and communal principles, we highlight the need for meta-scientific initiatives that prioritize and train undeveloped ethical virtues and strengthen those already present among scientists.

Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualised meditation practices and designed various meditation interventions (MIs), that have shown therapeutic efficacy for disorders including depression, pain, addiction, and anxiety. Over the past decade, neuroimaging has examined the neuroscientific basis of meditation practices, effects, states, and outcomes for clinical and non-clinical populations. However, the generalizability and replicability of current neuroscientific models of meditation are yet to be established, as they are largely based on small datasets entrenched with heterogeneity along several domains of meditation (e.g., practice types, meditation experience, clinical disorder targeted), experimental design, and neuroimaging methods (e.g., preprocessing, analysis, task-based, resting-state, structural MRI). These limitations have precluded a nuanced and rigorous neuroscientific phenotyping of meditation practices and their potential benefits. Here, we present ENIGMA-Meditation, the first worldwide collaborative consortium for neuroscientific investigations of meditation practices. ENIGMA-Meditation will enable systematic meta- and mega-analyses of globally distributed neuroimaging datasets of meditation using shared, standardized neuroimaging methods and tools to improve statistical power and generalizability. Through this powerful collaborative framework, existing neuroscientific accounts of meditation practices can be extended to generate novel and rigorous neuroscientific insights, accounting for multi-domain heterogeneity. ENIGMA-Meditation will inform neuroscientific mechanisms underlying therapeutic action of meditation practices on psychological and cognitive attributes, advancing the field of meditation and contemplative neuroscience.

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety cues across multiple datasets. We further show that many neural nodes dynamically shift representations between threat and safety. Our results establish reproducible decoders that integrate neural circuits, merging the well-characterized ‘threat circuit’ with sensory and cognitive nodes, discriminating threat from safety regardless of experimental designs or data acquisition parameters.

Background: The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program.Methods: We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27).Results: The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement.Conclusions: Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.