Proceedings of the National Academy of Sciences of the United States of America
September 8, 2026
Andrian G Basargin, Andras Domokosa, Joseph J. Hennessey et al.
Of the classic psychedelics, lysergic acid diethylamide (LSD) is perhaps the best-known, but its complex chemical architecture has limited synthetic investigations aimed at generating analogues with improved safety and efficacy profiles. Here, we systematically deconstruct the tetracyclic ergoline core of LSD to create 9 simplified ergoline analogues (i.e., ergologs) and evaluate them in...
Proceedings of the National Academy of Sciences of the United States of America
June 16, 2026
Adam R Pines, Xue Zhang, John Kochalka et al.
Psychedelic drugs are poised to become mainstream treatments, yet we lack a circuit-level account of how they reshape brain activity. Emerging evidence suggests that multiple psychedelic compounds modulate activity in the brain's default mode network (DMN), often interpreted as either increased or decreased bottom-up hierarchical processing. Most imaging studies, however, quantify activity as...
Proceedings of the National Academy of Sciences of the United States of America
May 5, 2026
Roberto Malinow
Ketamine has been shown to reduce depression and suicidality in individuals resistant to treatment by other drugs. Exactly how ketamine works is not known. Here, I propose a new hypothesis that involves synaptic and circuit plasticity and may lead to enhanced efficacy in treating depression as well as other conditions.
Proceedings of the National Academy of Sciences of the United States of America
April 14, 2026
Meichao Zhang, Casey Paquola, Katya Krieger-Redwood et al.
Everyday cognition depends on the brain's capacity to shift between sensing the external world and constructing it from memory. To achieve this, large-scale cortical systems must flexibly integrate incoming sensory signals with internally generated representations. Here, we show that this flexibility is reflected in the macroscale architecture of the default mode network (DMN). Using convergent...
Proceedings of the National Academy of Sciences of the United States of America
April 6, 2026
Tessa M. Benson-Greenwald, Avital Pelakh, Michael J. Tumminia et al.
Significance Many college students experience introductory physics courses as psychologically threatening contexts. Yet, succeeding in these high-stakes gateway courses is necessary to declare majors in engineering and physical sciences. We tested whether mindfulness, which centers attention to subjective experiences, can help provide students with tools to navigate their physics-related...
Proceedings of the National Academy of Sciences of the United States of America
March 10, 2026
François Leroy, Shruti Naik, Rasa Gulbinaite et al.
In the first months postterm, human infants are traditionally viewed as passive to their environment, unable to focus or sustain attention on specific objects. Here, we asked whether 4-mo-old infants could engage their attention strongly enough in a visual task to block the perception of a subsequent interesting stimulus-a phenomenon known as attentional blink, which in adults reflects a serial...
Proceedings of the National Academy of Sciences of the United States of America
December 30, 2025
Esteban Munoz-Musat, Arthur Le Coz, Andrew W. Corcoran et al.
5 citations
Does being awake necessarily mean being conscious of something? This study investigates the phenomenon of mind blanking (MB), characterized by an "emptiness of mind," comparing it with mind wandering (MW) and on-task (ON) states. Using a sustained attention task and electroencephalogram monitoring, behavioral, and neurophysiological signatures of MB were examined in 62 participants. MB...
Proceedings of the National Academy of Sciences of the United States of America
December 30, 2025
Catherine Hume, Carrie Cuttler, Samantha L Baglot et al.
With approximately 4% of the world's population using cannabis, there is a need to better understand its physiological effects. Cannabis consumption acutely promotes food intake ("the munchies") via delta-9-tetrahydrocannabinol-mediated activation of cannabinoid 1 receptors (CB1R); however, these appetitive effects have not been well characterized. We examined effects of cannabis vapor...
Proceedings of the National Academy of Sciences of the United States of America
December 9, 2025
Renzo C Lanfranco, Sucharit Katyal, August Hägerdal et al.
Conscious awareness refers to the subjective experience of perceiving, thinking, and feeling and the ability to report these experiences. These perceptions and thoughts are experienced as bound to an individual self. A fundamental aspect of this self-consciousness is the sense of bodily self-the experience of one's physical presence distinct from the external world, serving as the spatial...
Proceedings of the National Academy of Sciences of the United States of America
December 9, 2025
Bryce A. Keating, David R. Vago, Kilian Hett et al.
Neurofluids, including cerebrospinal fluid (CSF) and interstitial fluid, circulate through regulated central nervous system pathways to clear cerebral waste and support brain health, with elevated CSF flow hyperdynamicity and regurgitation through the cerebral aqueduct associating with aging and neurodegeneration. Sleep exerts state-dependent effects on neurofluid circulation, yet similar...
Proceedings of the National Academy of Sciences of the United States of America
May 13, 2025
Sijia Gao, Yelena Bibineyshvili, Seyed A Safavynia et al.
While current arousal level assessments in patients with disorders of consciousness discriminate altered states of consciousness, there are significant limitations in characterizing the transition from one state to another or quantifying the frequent arousal level fluctuations observed in a patient. Here, we identified a repeated, temporally discrete, dynamical pattern evident in the recovery...
Proceedings of the National Academy of Sciences of the United States of America
April 22, 2025
Irina Topchiy, Bernat Kocsis
Brain oscillations in different behavioral states are essential for cognition, and oscillopathies contribute to cognitive dysfunction in neuropsychiatric diseases. Cannabis-1 receptor (CB1-R) activation was reported to suppress theta and fast gamma activities in rats during waking exploration, and here, we show that cannabis fundamentally alters network activity during sleep as well. Prominent...
Proceedings of the National Academy of Sciences of the United States of America
March 18, 2025
Yusuke Moriguchi, Ryoichi Watanabe, Chifumi Sakata et al.
13 citations
Examination of the subjective qualitative aspects of an experience, or "qualia" in short, is a fundamental and core aspect of consciousness research. How can we characterize the particular quality of redness, i.e. a red quale? Based on a recent proposal of the structural characterization of qualia, which did not rely on verbal descriptions, we developed a task that obtained pairwise similarity...
Proceedings of the National Academy of Sciences of the United States of America
February 11, 2025
Christina Maher, Lea Tortolero, Soyeon Jun et al.
7 citations
Meditation is an accessible mental practice associated with emotional regulation and well-being. Loving-kindness meditation (LKM), a specific subtype of meditative practice, involves focusing one's attention on thoughts of well-being for oneself and others. Meditation has been proven to be beneficial in a variety of settings, including therapeutic applications, but the neural activity...
Proceedings of the National Academy of Sciences of the United States of America
October 15, 2024
Yihan Sophy Xiong, Jacob Donoghue, Mikael Lundqvist et al.
32 citations
Predictive coding is a fundamental function of the cortex. The predictive routing model proposes a neurophysiological implementation for predictive coding. Predictions are fed back from the deep-layer cortex via alpha/beta (8 to 30 Hz) oscillations. They inhibit the gamma (40 to 100 Hz) and spiking that feed sensory inputs forward. Unpredicted inputs arrive in circuits unprepared by alpha/beta,...
Proceedings of the National Academy of Sciences of the United States of America
May 28, 2024
Elie Adam, Marek Kowalski, Oluwaseun Akeju et al.
30 citations
Ketamine is an N-methyl-D-aspartate (NMDA)-receptor antagonist that produces sedation, analgesia, and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma oscillations (>25 Hz) in the electroencephalogram (EEG). The gamma oscillations are interrupted by slow-delta oscillations (0.1 to 4 Hz) at high doses....
Proceedings of the National Academy of Sciences of the United States of America
March 19, 2024
Hyuk-June Moon, Louis Albert, Emanuela De Falco et al.
9 citations
Grid cells in the entorhinal cortex (EC) encode an individual's location in space, integrating both environmental and multisensory bodily cues. Notably, body-derived signals are also primary signals for the sense of self. While studies have demonstrated that continuous application of visuo-tactile bodily stimuli can induce perceptual shifts in self-location, it remains unexplored whether these...
Proceedings of the National Academy of Sciences of the United States of America
November 27, 2023
John H. Krystal, Alfred P. Kaye, Sarah J. Jefferson et al.
66 citations
Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy for treatment-resistant symptoms, and protection against relapse distinguish it from prior antidepressants. Its discovery emerged from a reconceptualization of the neurobiology of depression and, in turn, insights from the elaboration of its mechanisms of action...
Proceedings of the National Academy of Sciences of the United States of America
November 14, 2023
Brandon R Munn, Eli J Müller, Jaan Aru et al.
Understanding the neurobiological mechanisms underlying consciousness remains a significant challenge. Recent evidence suggests that the coupling between distal-apical and basal-somatic dendrites in thick-tufted layer 5 pyramidal neurons (L5PN), regulated by the nonspecific-projecting thalamus, is crucial for consciousness. Yet, it is uncertain whether this thalamocortical mechanism can support...
Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers....
Proceedings of the National Academy of Sciences of the United States of America
November 1, 2022
Péter Simor, Tamás Bogdány, Philippe Peigneux
23 citations
Lucid dreaming (LD) is a mental state in which we realize not being awake but are dreaming while asleep. It often involves vivid, perceptually intense dream images as well as peculiar kinesthetic sensations, such as flying, levitating, or out-of-body experiences. LD is in the cross-spotlight of cognitive neuroscience and sleep research as a particular case to study consciousness, cognition, and...
Proceedings of the National Academy of Sciences of the United States of America
September 27, 2022
Konstantin Volzhenin, Jean-Pierre Changeux, Guillaume Dumas
Several neuronal mechanisms have been proposed to account for the formation of cognitive abilities through postnatal interactions with the physical and sociocultural environment. Here, we introduce a three-level computational model of information processing and acquisition of cognitive abilities. We propose minimal architectural requirements to build these levels, and how the parameters affect...
Proceedings of the National Academy of Sciences of the United States of America
May 3, 2022
Michael S A Graziano
This article argues that consciousness has a logically sound, explanatory framework, different from typical accounts that suffer from hidden mysticism. The article has three main parts. The first describes background principles concerning information processing in the brain, from which one can deduce a general, rational framework for explaining consciousness. The second part describes a...
Proceedings of the National Academy of Sciences of the United States of America
July 29, 2021
L. Blum, M. Blum
Significance This paper provides evidence that a theoretical computer science (TCS) perspective can add to our understanding of consciousness by providing a simple framework for employing tools from computational complexity theory and machine learning. Just as the Turing machine is a simple model to define and explore computation, the Conscious Turing Machine (CTM) is a simple model to define...
Proceedings of the National Academy of Sciences of the United States of America
July 23, 2021
Lennart R.b. Spindler, Andrea I. Luppi, Ram Adapa et al.
Significance Understanding the neural bases of consciousness is of basic scientific and clinical importance. Human neuroimaging has established that a network of interconnected brain regions known as the default mode network disintegrates in anesthesia and after brain damage that causes disorders of consciousness. However, the neurochemical underpinnings of this network change remain largely...