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Evidence from post-mortem, genetic, neuroimaging, and non-human animal research suggests that Major Depressive Disorder (MDD) is associated with abnormalities in brain myelin content. Brain regions implicated in this research, and in MDD more generally, include the nucleus accumbens (NAcc), lateral prefrontal cortex (LPFC), insula, subgenual anterior cingulate cortex (sgACC), and medial prefrontal cortex (mPFC). We examined whether MDD is characterized by reduced myelin at the whole-brain level and in NAcc, LPFC, insula, sgACC, and mPFC. Quantitative magnetic resonance imaging (qMRI) permits the assessment of myelin content, in vivo , in the human brain through the measure of R1. In this study we used qMRI to measure R1 in 40 MDD and 40 healthy control (CTL) participants. We found that the MDD participants had lower levels of myelin than did the CTL participants at the whole-brain level and in the NAcc, and that myelin in the LPFC was reduced in MDD participants who had experienced a greater number of depressive episodes. Although further research is needed to elucidate the role of myelin in affecting emotional, cognitive, behavioral, and clinical aspects of MDD, the current study provides important new evidence that a fundamental property of brain composition, myelin, is altered in this disorder.

Individuals experience reward not only when directly receiving positive outcomes (e.g., food or money), but also when observing others receive such outcomes. This latter phenomenon, known as vicarious reward, is a perennial topic of interest among psychologists and economists. More recently, neuroscientists have begun exploring the neuroanatomy underlying vicarious reward. Here we present a quantitative whole-brain meta-analysis of this emerging literature. We identified 25 functional neuroimaging studies that included contrasts between vicarious reward and a neutral control, and subjected these contrasts to an activation likelihood estimate (ALE) meta-analysis. This analysis revealed a consistent pattern of activation across studies, spanning structures typically associated with the computation of value (especially ventromedial prefrontal cortex) and mentalizing (including dorsomedial prefrontal cortex and superior temporal sulcus). We further quantitatively compared this activation pattern to activation foci from a previous meta-analysis of personal reward. Conjunction analyses yielded overlapping VMPFC activity in response to personal and vicarious reward. Contrast analyses identified preferential engagement of the nucleus accumbens in response to personal as compared to vicarious reward, and in mentalizing-related structures in response to vicarious as compared to personal reward. These data shed light on the common and unique components of the reward that individuals experience directly and through their social connections. [Display omitted] •We compare quantitative meta-analyses of personal and vicarious (vic.) reward.•Vic. reward studies activate regions related to value computation and mentalizing.•Vic. and personal reward studies commonly activate ventromedial PFC.•Personal as compared to vic. reward preferentially engages nucleus accumbens.•Vic. versus personal reward preferentially engages regions related to mentalizing.

Neuroimaging methods with enhanced spatial resolution such as functional magnetic resonance imaging (FMRI) suggest that the subcortical striatum plays a critical role in human reward processing. Analysis of FMRI data requires several preprocessing steps, some of which entail tradeoffs. For instance, while spatial smoothing can enhance statistical power, it may also bias localization towards regions that contain more gray than white matter. In a meta-analysis and reanalysis of an existing dataset, we sought to determine whether spatial smoothing could systematically bias the spatial localization of foci related to reward anticipation in the nucleus accumbens (NAcc). An activation likelihood estimate (ALE) meta-analysis revealed that peak ventral striatal ALE foci for studies that used smaller spatial smoothing kernels (i.e. <6mm FWHM) were more anterior than those identified for studies that used larger kernels (i.e. >7mm FWHM). Additionally, subtraction analysis of findings for studies that used smaller versus larger smoothing kernels revealed a significant cluster of differential activity in the left relatively anterior NAcc (Talairach coordinates: −10, 9, −1). A second meta-analysis revealed that larger smoothing kernels were correlated with more posterior localizations of NAcc activation foci (p<0.015), but revealed no significant associations with other potentially relevant parameters (including voxel volume, magnet strength, and publication date). Finally, repeated analysis of a representative dataset processed at different smoothing kernels (i.e., 0–12mm) also indicated that smoothing systematically yielded more posterior activation foci in the NAcc (p<0.005). Taken together, these findings indicate that spatial smoothing can systematically bias the spatial localization of striatal activity. These findings have implications both for historical interpretation of past findings related to reward processing and for the analysis of future studies. ► Localization of striatal FMRI activity is systematically biased by spatial smoothing. ► Two meta-analytic techniques and reprocessing of a dataset support this claim. ► These findings have implications for interpreting reward processing studies. ► These findings also have implications for conducting future studies.

•Advanced meditative frameworks such as the stages of insight (SoI) remain understudied despite their potential for supporting mental health.•SoI deactivated brain regions associated with self-related processing and activated regions associated with perception and perceptual sensitivity.•Levels of equanimity correlated with deactivations in the medial prefrontal cortex and activations in the posterior cingulate cortex. The stages of insight (SoI) are a series of psychological realizations experienced through advanced investigative insight meditation (AIIM). SoI provide a powerful structured framework of AIIM for understanding and evaluating insight-based meditative development through changes in perception, experiences of self, cognition, and emotional processing. Yet, the neurophenomenology of SoI remains unstudied due to methodological difficulties, rarity of suitable advanced meditation practitioners, and dominant research emphasis on attention-based meditative practices. We investigated the neurophenomenology of SoI in an intensively sampled adept meditator case study (4 hr 7T fMRI collected in 26 runs with concurrent phenomenology) who performed SoI and rated specific aspects of experience immediately thereafter. Linear mixed models and correlations were used to examine relations among the cortex, subcortex, brainstem, and cerebellum, and SoI phenomenology. We identified distinctive whole-brain activity patterns associated with specific SoI, and that were different from two non-meditative control states. SoI consistently deactivated regions implicated in self-related processing, including the medial prefrontal cortex and temporal poles, while activating regions associated with awareness and perception, including the parietal and visual cortices, caudate, several brainstem nuclei, and cerebellum. Patterns of brain activity related to affective processing and SoI phenomenology were also identified. Our study presents the first neurophenomenological evidence that SoI shifts and deconstructs self-related perception and conceptualization, and increases general awareness and perceptual sensitivity and acuity. Our study provides SoI as a foundation for investigative, and advanced meditation in particular. [Display omitted]

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD‐related differences in subcortical regions using shape analysis. In this meta‐analysis of subcortical shape from the ENIGMA‐MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta‐analysis. Relative to CTL, patients with adolescent‐onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = −0.164 to −0.180). Relative to first‐episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = −0.173 to −0.184). Our results suggest that previously reported MDD‐associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

Millions of people globally have learned mindfulness meditation with the goal of improving health and well-being outcomes in both clinical and non-clinical contexts. An estimated half of these practitioners follow mindfulness teachers’ recommendations to continue regular meditation after completion of initial instruction, but it is unclear whether benefits are strengthened by regular practice and whether harm can occur. Increasing evidence shows a wide range of experiences that can arise with regular mindfulness meditation, from profoundly positive to challenging and potentially harmful. Initial research suggests that complex interactions and temporal sequences may explain these experiential phenomena and their relations to health and well-being. We believe further study of the effects of mindfulness meditation is urgently needed to better understand the benefits and challenges of continued practice after initial instructions. Effects may vary systematically over time due to factors such as initial dosage, accumulation of ongoing practice, developing skill of the meditator, and complex interactions with the subjects’ past experiences and present environment. We propose that framing mindfulness meditation experiences and any associated health and well-being benefits within integrated longitudinal models may be more illuminating than treating them as discrete, unrelated events. We call for ontologically agnostic, collaborative, and interdisciplinary research to study the effects of continued mindfulness meditation and their contexts, advancing the view that practical information found within religious and spiritual contemplative traditions can serve to develop initial theories and scientifically falsifiable hypotheses. Such investigation could inform safer and more effective applications of mindfulness meditation training for improving health and well-being.

Repetitive transcranial magnetic stimulation (rTMS) has gained considerable importance in the treatment of neuropsychiatric disorders, including major depression. However, it is not yet understood how rTMS alters brain’s functional connectivity. Here we report changes in functional connectivity captured by resting state functional magnetic resonance imaging (rsfMRI) within the first hour after 10 Hz rTMS. We apply subject-specific parcellation schemes to detect changes (1) in network nodes, where the strongest functional connectivity of regions is observed, and (2) in network boundaries, where functional transitions between regions occur. We use support vector machine (SVM), a widely used machine learning algorithm that is robust and effective, for the classification and characterization of time intervals of changes in node and boundary maps. Our results reveal that changes in connectivity at the boundaries are slower and more complex than in those observed in the nodes, but of similar magnitude according to accuracy confidence intervals. These results were strongest in the posterior cingulate cortex and precuneus. As network boundaries are indeed under-investigated in comparison to nodes in connectomics research, our results highlight their contribution to functional adjustments to rTMS.

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers (www.psymri.com). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

•This multimodal [ultra-high-field 7T MRI, electroencephalography (fMRI-EEG)] intensively sampled neurophenomenological study in a rare adept meditator offers the most comprehensive view of the brain dynamics of advanced concentration meditation.•Global hyperconnectivity, collapsed modular integrity of the brain's functional networks (fMRI), widespread decreases in broadband EEG oscillatory power, and increases in Lempel-Ziv complexity (LZ, a measure of entropy) were observed during these meditative states – metrics that also correlated with the blissful experience.•These results enrich our understanding of these advanced meditative states and support the notion that advanced meditation may deconstruct the hierarchical organization of the brain's function. Using a combination of fMRI, EEG, and phenomenology ratings, we examined the neurophenomenology of advanced concentrative absorption meditation, namely jhanas (ACAM-J), in a practitioner with over 23,000 h of meditation practice. Our study shows that ACAM-J states induce reliable changes in conscious experience and that these experiences are related to neural activity. Using resting-state fMRI functional connectivity, we found that ACAM-J is associated with decreased within-network modularity, increased global functional connectivity (GFC), and desegregation of the default mode and visual networks. Compared to control tasks, the ACAM-J were also related to widespread decreases in broadband EEG oscillatory power and increases in Lempel-Ziv complexity (LZ, a measure of brain entropy). Some fMRI findings varied by the control task used, while EEG results remained consistent, emphasizing both shared and unique neural features of ACAM-J. These differences in fMRI and EEG-measured neurophysiological properties correlated with specific changes in phenomenology – and especially with ACAM-J-induced states of bliss - enriching our understanding of these advanced meditative states. Our results show that advanced meditation practices markedly dysregulate high-level brain systems via practices of enhanced attention to sensations, corroborating recent neurocognitive theories of meditation as the deconstruction of the brain's cortical hierarchy. Overall, our results suggest that ACAM-J is associated with the modulation of large-scale brain networks in both fMRI and EEG, with potential implications for understanding the mechanisms of deep concentration practices and their effects on subjective experience. [Display omitted]

Psychedelic substances induce profound alterations in consciousness. Careful preparation is therefore essential to limit adverse reactions, enhance therapeutic benefits, and maintain user safety. This paper describes the development of a self-directed, digital intervention for psychedelic preparation. Drawing on elements from the UK Medical Research Council (MRC) framework for developing complex interventions, the design was informed by a four-factor model of psychedelic preparedness, using a person-centred approach. Our mixed-methods investigation consisted of two studies. The first involved interviews with 19 participants who had previously attended a ‘high-dose’ psilocybin retreat, systematically exploring their preparation behaviours and perspectives on the proposed intervention. The second study engaged 28 attendees of an ongoing psilocybin retreat in co-design workshops, refining the intervention protocol using insights from the initial interviews. The outcome is a co-produced 21-day digital course (Digital Intervention for Psychedelic Preparation (DIPP)), that is organised into four modules: Knowledge–Expectation, Psychophysical–Readiness, Safety–Planning, and Intention–Preparation. Fundamental components of the course include daily meditation practice, supplementary exercises tied to the weekly modules, and mood tracking. DIPP provides a comprehensive and scalable solution to enhance psychedelic preparedness, aligning with the broader shift towards digital mental health interventions.