Proceedings of the National Academy of Sciences
October 11, 2007
Yi-Yuan Tang, Yinghua Ma, Junhong Wang et al.
1,585 citations
Five days of brief, daily meditation using the integrative body-mind training method improved attention and reduced stress more than relaxation training alone. In a randomized experiment with 40 undergraduate Chinese students, those who practiced 20 minutes of integrative meditation for five days showed greater improvement on the Attention Network Test, lower anxiety, depression, anger, and fatigue, higher vigor, reduced cortisol, and increased immunoreactivity compared to a relaxation control group. The findings suggest that even short-term meditation can produce measurable cognitive and physiological benefits, offering a practical way to study meditation using controlled experimental designs.
Proceedings of the National Academy of Sciences
November 23, 2011
Judson A. Brewer, Patrick D. Worhunsky, Jeremy R. Gray et al.
1,410 citations
Experienced meditators show reduced activity in brain regions linked to self-referential thought and mind-wandering, particularly the medial prefrontal and posterior cingulate cortices, across different meditation types. They also exhibit stronger connections between areas involved in self-monitoring and cognitive control, such as the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices, both at rest and during meditation. These neural patterns align with decreased mind-wandering, offering insight into how meditation may support present-moment awareness and well-being.
Proceedings of the National Academy of Sciences
November 8, 2004
Antoine Lutz, Lawrence L. Greischar, Nancy B. Rawlings et al.
1,325 citations
Long-term Buddhist practitioners can self-induce sustained, high-amplitude gamma-band oscillations and phase-synchrony in the brain during meditation, as measured by electroencephalography. These EEG patterns differ from those of non-practitioners, especially over lateral frontoparietal electrodes. Before meditation, practitioners already show a higher ratio of gamma-band activity (25-42 Hz) to slow oscillatory activity (4-13 Hz) over medial frontoparietal electrodes compared to controls. This ratio increases sharply during meditation across most of the scalp and remains elevated afterward. The findings suggest that mental training involves temporal integrative mechanisms and may produce both short-term and long-term neural changes.
Proceedings of the National Academy of Sciences
January 23, 2012
Alessandro Colasanti, Robin J. Tyacke, Robert Leech et al.
1,191 citations
Psychedelic drugs like psilocybin, found in magic mushrooms, produce profound changes in consciousness by decreasing activity and connectivity in key brain hub regions. Using functional MRI, researchers observed that psilocybin reduced cerebral blood flow and BOLD signal, especially in the thalamus, anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC). Decreased activity in the ACC and medial prefrontal cortex (mPFC) predicted the intensity of subjective psychedelic effects. Psilocybin also reduced positive coupling between the mPFC and PCC. These findings suggest that psychedelics work by dampening the brain's connector hubs, leading to a state of unconstrained cognition.
Proceedings of the National Academy of Sciences
June 28, 2007
Julie A. Brefczynski‐Lewis, Antoine Lutz, Hillary S. Schaefer et al.
988 citations
Meditation is a family of mental training practices that familiarize practitioners with specific mental processes. In age-matched participants, using functional MRI, activation in brain regions involved in sustained attention showed an inverted u-shaped curve: expert meditators with an average of 19,000 hours of practice had more activation than novices, but experts with an average of 44,000 hours had less activation. In response to distracter sounds, experts versus novices had less brain activation in regions related to discursive thoughts and emotions and more activation in regions related to response inhibition and attention. Correlation with hours of practice suggests possible plasticity in these mechanisms.
Proceedings of the National Academy of Sciences
June 19, 2009
Silvina G. Horovitz, Allen R. Braun, Walter S. Carr et al.
706 citations
A natural reduction of consciousness during sleep alters the correlation between components of the default-mode network (DMN), particularly reducing the involvement of frontal cortex. This suggests the DMN may play an important role in sustaining conscious awareness. The finding contrasts with a recent study in anesthetized primates that proposed DMN activity reflects general network dynamics rather than conscious mentation.
Proceedings of the National Academy of Sciences
December 13, 2005
Gabriella Gobbi, Francis Rodriguez Bambico, Regina A. Mangieri et al.
675 citations
Inhibiting the enzyme fatty-acid amide hydrolase (FAAH) with URB597, which prevents the breakdown of the endocannabinoid anandamide, produces antidepressant-like effects in mice and rats. URB597 reduced immobility in the tail-suspension and forced-swim tests, and increased firing of serotonin and norepinephrine neurons in brain regions linked to mood. These effects required CB1 receptor activation and were accompanied by higher brain anandamide levels. Unlike direct THC-like drugs, URB597 showed no rewarding or abuse-related effects. The findings suggest FAAH inhibition as a potential target for antidepressant drugs without the psychotropic side effects of cannabis.
Proceedings of the National Academy of Sciences
February 21, 2012
Hanbing Lu, Qihong Zou, Hong Gu et al.
627 citations
A brain network called the default mode network (DMN), previously studied mainly in humans and primates, also exists in rats. The DMN in rats is broadly similar to that in nonhuman primates and humans, suggesting it is a fundamental feature of mammalian brains. The network appears to integrate sensory and emotional information to guide behavior in anticipation of changing environmental conditions, despite the distinct evolutionary paths of rodents and primates. The findings help clarify the DMN's core functions, which remain poorly understood in humans.
Proceedings of the National Academy of Sciences
March 1, 1992
Gary Rudnick, S C Wall
533 citations
MDMA (ecstasy) acts on serotonin transporters in both the plasma membrane and secretory vesicles. In plasma membrane vesicles from human platelets, MDMA inhibits serotonin transport and imipramine binding by directly interacting with the sodium-dependent serotonin transporter, and it stimulates serotonin efflux in a stereo-specific, sodium-dependent, and imipramine-sensitive manner via transporter-mediated exchange. In vesicles from bovine adrenal chromaffin granules containing the vesicular biogenic amine transporter, MDMA inhibits ATP-dependent serotonin accumulation and stimulates efflux by dissipating the transmembrane pH difference and directly interacting with the vesicular transporter.
Proceedings of the National Academy of Sciences
January 22, 2002
Antoine Lutz, Jean-Philippe Lachaux, Jacques Martinerie et al.
500 citations
Brain responses to identical stimuli vary greatly even during well-designed cognitive tasks, and this variability is thought to stem from fluctuations in a person's cognitive context—such as attention, spontaneous thoughts, and task strategy. By combining first-person reports with neural recordings, researchers reduced this noise. Subjects viewed a three-dimensional illusion while their brain activity was recorded and they reported their cognitive context. Clustering trials by these reports revealed that patterns of neural synchrony in frontal electrodes before stimulation depended on the degree of preparation and immediacy of perception. These patterns were stable across recordings and influenced both behavioral performance and subsequent brain responses, showing that first-person data can help detect and interpret neural processes.
Proceedings of the National Academy of Sciences
April 13, 2021
Natalie Hesselgrave, Timothy A. Troppoli, Andreas B. Wulff et al.
380 citations
Psilocybin, a psychedelic compound, has fast-acting antidepressant-like effects in mice. Using tests of hedonic behavior and a drug that blocks hallucinogenic 5-HT2A receptors, the results suggest that altered perception may not be required for its therapeutic benefits. Psilocybin also strengthens connections between brain cells in regions involved in reward and emotion processing. These findings indicate it may be possible to retain psilocybin's antidepressant actions while minimizing alterations in consciousness.
Proceedings of the National Academy of Sciences
July 5, 2006
Anil K. Seth, Eugene M. Izhikevich, George N. Reeke et al.
327 citations
No single quantitative measure—neural complexity, information integration, or causal density—fully captures the multidimensional complexity of the neural systems underlying consciousness, and each has practical limitations. The analysis suggests that combining alternative measures may improve quantitative characterization, but some aspects of consciousness likely resist quantification entirely, so a satisfactory theory should blend qualitative and quantitative elements.
Proceedings of the National Academy of Sciences
April 13, 2020
Morten L. Kringelbach, Josephine Cruzat, Joana Cabral et al.
326 citations
By combining multimodal neuroimaging data, a framework was developed that demonstrates the fundamental principles of bidirectional coupling between neuronal and neurotransmitter dynamical systems. The work causally explains the functional effects of stimulating specific serotoninergic receptors (5-HT2AR) with psilocybin in healthy humans. This could lead to a better understanding of why psilocybin shows promise as a therapeutic intervention for neuropsychiatric disorders such as depression, anxiety, and addiction.
Proceedings of the National Academy of Sciences
August 27, 2018
Mladen Sormaz, Charlotte Murphy, Hao-ting Wang et al.
291 citations
The default mode network (DMN), a set of brain regions traditionally linked to off-task or mind-wandering states, actually contributes to detailed, task-relevant cognition during active tasks. Using fMRI, participants performed working-memory tasks while reporting their thoughts. Patterns of neural activity showed that distinctions between on- and off-task thought involved regions near sensory and motor cortex, not the DMN. However, the level of detail in ongoing thought corresponded to activity patterns within the DMN during memory maintenance. These findings indicate the DMN supports detailed cognition under active task conditions, challenging the view that it is solely task-negative.
Proceedings of the National Academy of Sciences
September 3, 2013
Enzo Tagliazucchi, Frederic von Wegner, Astrid Morzelewski et al.
278 citations
A conscious brain integrates information across segregated functional modules and also maintains long-term memory in its neural activity. This study examined temporal memory in blood oxygen level-dependent signals across the human nonrapid eye movement sleep cycle. Temporal dependence gradually decreased from wakefulness to deep nonrapid eye movement sleep, particularly in default mode and attention networks. Although spatial organization of spontaneous fluctuations remained nontrivial even during deep sleep, temporal complexity decreased in specific brain regions. These findings suggest that long-range temporal dependence may be a characteristic of the spontaneous conscious mentation that occurs during wakeful rest.
Proceedings of the National Academy of Sciences
December 15, 2014
James M. Stafford, Benjamin R. Jarrett, Oscar Miranda-Dominguez et al.
261 citations
Resting-state functional connectivity MRI (rs-fcMRI) can be reliably performed in mice, producing high-resolution whole-brain images. The functional connections strongly align with the brain's structural wiring, as mapped by anterograde tracer studies. Large-scale network properties previously seen only in primates also exist in rodents, though with some differences. A potential default mode network (DMN)—a system important for social cognition and disrupted in many disorders—was identified in the mouse brain both structurally and functionally. These findings validate mouse rs-fcMRI as a translational bridge, allowing stronger links between cellular and molecular manipulations in mice and human brain conditions.
Proceedings of the National Academy of Sciences
September 25, 2012
Alan Anticevic, Mark G. Gancsos, John D. Murray et al.
260 citations
Glutamate signaling through NMDA receptors is essential for brain computations that support cognition, and its disruption may contribute to schizophrenia. Using ketamine, an NMDA receptor antagonist, the study found that the normal anticorrelation between the default-mode and task-positive brain systems was disrupted during a working memory task. The degree of this disruption predicted task performance and produced schizophrenia-like symptoms. A computational model suggests that cortical disinhibition underlies this effect, linking glutamate's role in large-scale brain organization to cognition and psychiatric symptoms.
Proceedings of the National Academy of Sciences
March 17, 1998
Giulio Tononi, Ramesh Srinivasan, D. Patrick Russell et al.
259 citations
During binocular rivalry, where each eye sees a different image but only one is consciously perceived at a time, neuromagnetic responses in the brain show activity at frequencies corresponding to both stimuli, even for the unseen one. However, when a stimulus is not consciously perceived, the power of its neural response is reduced by 50-85% across many brain regions, including areas outside the visual cortex. This modulation is widespread but not global, indicating that conscious perception correlates with the strength of synchronized neural activity in large neuronal populations.
Proceedings of the National Academy of Sciences
December 24, 2012
Tamami Nakano, Makoto Kato, Yusuke Morito et al.
246 citations
Spontaneous eyeblinks occur more often than needed to keep the eyes moist. While people watch videos, blinks tend to happen at natural breakpoints in attention. Brain scans show that immediately after a blink, activity briefly drops in the dorsal attention network and rises in the default-mode network, which is linked to internal thought. Physical blackouts of the video do not cause the same brain-network changes. This suggests that eyeblinks actively help disengage attention by momentarily shifting brain activity from external focus to internal processing.
Proceedings of the National Academy of Sciences
June 8, 2015
Gina F. Humphreys, Paul Hoffman, Maya Visser et al.
219 citations
The default mode network (DMN) and semantic network (SN) are thought to overlap in brain regions like the anterior temporal lobe (ATL) and angular gyrus (AG), but their relationship is rarely tested directly. Using fMRI data from 69 participants performing semantic and nonsemantic tasks, the authors found that both networks split into subparts depending on task demands, stimulus type, and difficulty. The left ATL was active for semantic tasks and deactivated for nonsemantic ones, while the left AG was deactivated for all tasks, with deactivation linked to difficulty. Thus, ATL and AG do not share a common role in semantic processing; instead, both are inactive during nonsemantic tasks. These findings challenge the idea that both regions are semantic hubs and have implications for understanding DMN variability and resting-state fMRI.
Proceedings of the National Academy of Sciences
November 4, 2009
Kelly A. Jones, Deepak P. Srivastava, John Allen et al.
215 citations
The 5-HT(2A) serotonin receptor, abundant in cortical pyramidal neurons and targeted by hallucinogens and psychiatric medications, is present in a subset of dendritic spines and colocalizes with PSD-95 and MUPP1. Activation by the agonist DOI transiently increases spine size and phosphorylates PAK, a downstream target of kalirin-7. Peptide interference preventing kalirin-7 localization to the postsynaptic density disrupts DOI-induced PAK phosphorylation and spine morphogenesis. These findings suggest serotonin signaling may modulate dendritic spine morphology through kalirin-7 at cortical synapses.
Proceedings of the National Academy of Sciences
March 26, 2012
Melanie Boly, Vincent Perlbarg, Guillaume Marrelec et al.
201 citations
Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM sleep is associated with an increased modularity of brain activity. Cerebral connectivity was quantified in resting-state functional magnetic resonance imaging times series acquired in 13 healthy volunteers during wakefulness and NREM sleep. The analysis revealed a modification of the hierarchical organization of large-scale networks into smaller independent modules during NREM sleep, independently from EEG markers of the slow oscillation. Such modifications in brain connectivity, possibly driven by sleep ultraslow oscillations, could hinder the brain's ability to integrate information and account for decreased consciousness during NREM sleep.
Proceedings of the National Academy of Sciences
January 21, 2020
Matthias Forstmann, Daniel Alexander Yudkin, Annayah Miranda Beatrice Prosser et al.
185 citations
Using psychedelic substances such as LSD or psilocybin is linked to improved mood and stronger feelings of social connectedness in naturalistic settings. Across six multiday mass gatherings in the United States and the United Kingdom, over 1,200 participants were studied. Those who had taken psychedelics reported higher positive mood, an effect that occurred sequentially through transformative experiences and then increased social connectedness. The association was strongest for people who had used psychedelics within the previous 24 hours compared to the past week. The findings provide robust evidence that psychedelic use can have positive affective and social consequences in real-world contexts.
Proceedings of the National Academy of Sciences
April 18, 2016
Katrin H. Preller, Thomas Pokorny, Andreas Hock et al.
175 citations
Social ties are crucial for health, but psychiatric patients often face social rejection, and heightened reactivity to exclusion affects disorder development and treatment. The neuromodulatory substrates of rejection are largely unknown. Psilocybin, a serotonin 5-HT2A/1A receptor agonist, reduces processing of negative stimuli, but its effect on negative social interactions was unclear. In a double-blind, randomized, cross-over study with 21 healthy volunteers, psilocybin (0.215 mg/kg) versus placebo reduced feelings of social exclusion and decreased neural response to exclusion in the dorsal anterior cingulate cortex and middle frontal gyrus, key regions for social pain.
Proceedings of the National Academy of Sciences
March 13, 2019
Panos Zanos, Jaclyn N. Highland, Brent W. Stewart et al.
153 citations
A single subanesthetic dose of ketamine produces rapid (within hours) and sustained antidepressant effects, unlike standard antidepressants that take months and fail in about 30% of patients. The ketamine metabolite (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] is a rapid-acting antidepressant candidate with fewer adverse effects. Using behavioral, genetic, pharmacological approaches and EEG measurements, the study found that antidepressant-relevant actions of (2R,6R)-HNK involve metabotropic glutamate receptor subtype 2 (mGlu2) signaling and identified high-frequency EEG oscillations as a marker of rapid antidepressant responses. The findings suggest clinical trials combining subtherapeutic doses of mGlu2 receptor inhibitors with ketamine or (2R,6R)-HNK for depression treatment.