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.
Cannabis vapor inhalation acutely increases food intake in both humans and rats, an effect driven by central cannabinoid 1 receptors. In humans, energy intake rose within the first 30 minutes of snack access, regardless of dose or gender, without altering the proportion of macronutrients consumed. In rats, cannabis vapor reduced the time to start eating and increased the number of feeding bouts, overriding homeostatic appetite regulation by boosting motivation to eat and reducing food reward devaluation. These feeding effects were not accompanied by changes in circulating appetite-associated hormones, and they depended on central, not peripheral, CB1 receptors.
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.
Mindfulness meditation may alter the flow of cerebrospinal fluid (CSF) in the brain in a way that resembles sleep and counters age-related changes. Using MRI, researchers measured CSF movement through the cerebral aqueduct and fluctuations near the cervicomedullary junction in meditation-naïve adults and adept meditators. During focused attention meditation, adept meditators showed decreased absolute CSF flow (from 4.60 to 4.17 mL/min) due to reduced backward flow, along with increased low-frequency CSF fluctuations that inversely correlated with gray matter fluctuations. No changes were seen in control groups. The findings suggest meditation could be a waking state that modulates neurofluid dynamics similarly to sleep and opposite to aging.
Proceedings of the National Academy of Sciences of the United States of America
April 22, 2025
Irina Topchiy, Bernat Kocsis
Cannabis fundamentally alters brain activity during sleep by activating CB1 receptors. In rats, a CB1 receptor agonist disrupted normal sleep patterns: intermediate sleep lengthened sixfold and intruded into REM sleep, while theta oscillations during REM were drastically reduced. Sleep spindle architecture also changed—spindle amplitude increased and peak frequency shifted downward into the theta range. These findings may help explain how cannabis produces both cognitive deficits and psychotic-like effects, and highlight the role of brain oscillations in psychiatric conditions.
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.
Integrated information, a proposed signature of consciousness, is maximized in a biophysical network model when the nonspecific thalamus drives thick-tufted layer 5 pyramidal neurons into a regime of time-varying synchronous bursting. In this regime, variable spiking dynamics with broad pairwise correlations support enhanced integrated information. The peak in integrated information coincides with criticality signatures and empirically observed layer 5 pyramidal bursting rates. These findings suggest that the thalamocortical core of the mammalian brain may be evolutionarily configured to optimize effective information processing, offering a potential neuronal mechanism linking microscale theories to macroscale signatures of consciousness.
Proceedings of the National Academy of Sciences of the United States of America
September 27, 2022
Konstantin Volzhenin, Jean-Pierre Changeux, Guillaume Dumas
A three-level computational model of information processing and cognitive development is introduced. The first sensorimotor level handles local nonconscious processing during a visual classification task. The second cognitive level globally integrates information via long-range connections, still nonconsciously. The third conscious level, based on global neuronal workspace theory, maintains self-sustained representations in the absence of sensory input, requiring interneurons. Results show that synaptic epigenesis—selection and stabilization of synapses at local and global scales—is necessary for solving trace and delay conditioning tasks. Dopamine enables credit assignment across temporal delays between perception and reward. Balanced spontaneous activity facilitates epigenesis, and a balanced excitatory/inhibitory ratio improves performance.
Proceedings of the National Academy of Sciences of the United States of America
May 3, 2022
Michael S A Graziano
Consciousness can be explained through a rational, scientific framework that avoids hidden mysticism. The Attention Schema Theory proposes that the brain constructs a simplified model of its own attention, which serves as the basis for conscious experience. Growing behavioral, brain imaging, and computational evidence supports this theory. Consciousness likely evolved gradually over millions of years, from fish to humans, because it plays specific adaptive roles in cognition and behavior, such as enabling flexible control of attention and social prediction.
Proceedings of the National Academy of Sciences of the United States of America
July 29, 2021
L. Blum, M. Blum
A theoretical computer science perspective can deepen understanding of consciousness. The Conscious Turing Machine (CTM) is a simple, substrate-independent computational model for defining and exploring consciousness, analogous to how the Turing machine models computation. The CTM is not a model of the brain or cognition but offers a framework using computational complexity theory and machine learning. This paper introduces the approach, demonstrates its possibilities, and aims to stimulate research on consciousness from a theoretical computer science viewpoint.
Proceedings of the National Academy of Sciences of the United States of America
July 23, 2021
L. R. Spindler, A. Luppi, R. Adapa et al.
A network of brain regions called the default mode network breaks down during anesthesia and after brain damage causing disorders of consciousness. The neurochemical reasons for this breakdown were unclear. Using functional MRI, researchers found that the ventral tegmental area, a dopamine-producing brainstem region, disconnects from key default mode network nodes (precuneus and posterior cingulate) during both propofol sedation and disorders of consciousness. Stronger connectivity between the ventral tegmental area and these nodes was associated with a more awake-like configuration of the default mode network. In patients with disorders of consciousness who later improved behaviorally, this connectivity increased toward healthy levels. In a separate group of traumatic brain injury patients, the drug methylphenidate significantly strengthened this connection. The findings suggest that dopamine modulation may be central to maintaining consciousness.
Proceedings of the National Academy of Sciences of the United States of America
June 30, 2021
L. Stiernman, F. Grill, A. Hahn et al.
Negative fMRI signals in the brain's default mode network (DMN) during cognitive control do not reflect a relative increase in synaptic activity during rest periods. Using hybrid PET-MRI, the study found that task-positive BOLD responses in attention and control networks align with increased glucose metabolism during cognitive control, but metabolism in the DMN remained high during both rest and task despite negative BOLD responses. This dissociation indicates that DMN BOLD responses are not simply the inverse of metabolic activity, challenging common interpretations and suggesting distinct neurovascular coupling in this network.
Proceedings of the National Academy of Sciences of the United States of America
June 11, 2021
K. Clancy, Jeremy A. Andrzejewski, Yuqi You et al.
Alpha-frequency transcranial alternating current stimulation (α-tACS) applied to the cortical source of alpha oscillations in healthy adults not only increased EEG alpha activity but also strengthened functional connectivity within the default mode network (DMN), with the alpha increase mediating the connectivity enhancement. The findings identify a mechanistic link between alpha oscillations and DMN functioning and highlight α-tACS as a noninvasive intervention to regulate the DMN, which is dysregulated in major neuropsychiatric disorders.
Proceedings of the National Academy of Sciences of the United States of America
June 15, 2020
J. Ferrier, E. Tiran, T. Deffieux et al.
Functional ultrasound imaging, which offers higher sensitivity and spatiotemporal resolution than fMRI, was validated for studying sensory stimulation-induced changes in the awake mouse brain. Using this approach in lightly sedated conscious mice, unilateral whisker stimulation activated the contralateral barrel cortex and reduced activity in the ipsilateral barrel cortex via interhemispheric inhibition, while also increasing bilateral hippocampal connectivity. During awake resting-state periods, whisker stimulation specifically reduced activation and interhemispheric correlation in the retrosplenial cortex, a major hub of the default mode network (DMN). These findings provide functional evidence for an evolutionarily preserved DMN function in mice, supporting the translational relevance of this preclinical model for neuropsychiatric diseases.
Proceedings of the National Academy of Sciences of the United States of America
March 31, 2020
Gaëtan Sanchez, Thomas Hartmann, Marco Fuscà et al.
Neural activity in primary sensory regions not directly relevant to a task can predict conscious perception of near-threshold stimulation in a different sensory modality. Using magnetoencephalography and multivariate decoding analysis across tactile, visual, and auditory tasks, supramodal spatiotemporal patterns were identified that predicted conscious perception. These patterns included activity in visual cortex predicting conscious perception of auditory stimuli. The findings were replicated in a control experiment and were independent of the type of report (button press or withholding a button press). The results suggest a common signature of conscious access across sensory modalities, involving temporally late and widespread broadcasting of neural representations.
Proceedings of the National Academy of Sciences of the United States of America
March 12, 2019
Marian Schneider, Valentin G Kemper, Thomas C Emmerling et al.
The conscious experience of seeing motion in a particular direction is linked to the activity of specialized neuron clusters in the brain's motion-processing area. Using high-resolution 7-tesla fMRI, researchers identified clusters of neurons in the human motion complex that responded preferentially to either horizontal or vertical motion. When participants viewed an ambiguous display that could be seen as moving either horizontally or vertically, their reported perceptions alternated every 7 to 13 seconds. The activity in the horizontal- and vertical-tuned clusters dissociatively reflected which direction the person perceived at any moment, even though the visual input remained constant. These clusters were organized in columns, with stable direction preferences through the depth of the cortex.
Proceedings of the National Academy of Sciences of the United States of America
February 11, 2019
Emily K. Lindsay, S. Young, K. Brown et al.
A two-week smartphone-based mindfulness training that teaches both monitoring of present-moment experiences and an orientation of acceptance reduced loneliness by 22% and increased social contact by about two more interactions and one more person each day among community adults. Training that taught monitoring alone did not produce these benefits, showing that developing acceptance skills is a critical mechanism for mitigating loneliness and social isolation. The findings point to a behavioral target for improving social-relationship functioning.
Proceedings of the National Academy of Sciences of the United States of America
September 17, 2018
Yoona Kang, N. Cooper, Prateekshit Pandey et al.
Activating a self-transcendent mindset—focusing on others' well-being through reflecting on values or making positive wishes—increased activity in brain regions linked to positive valuation and reward. Among 220 sedentary adults, those primed with self-transcendence before health messages showed greater objectively measured increases in physical activity over the following month. During message exposure, self-transcendence was associated with increased activity in ventromedial prefrontal cortex subregions involved in self-related processing and positive valuation, which predicted later decreases in sedentary behavior. The findings suggest that a positive, other-focused mindset can reduce defensiveness and increase receptivity to health information, promoting behavior change.
Proceedings of the National Academy of Sciences of the United States of America
September 11, 2018
Lauri Nummenmaa, Riitta Hari, Jari K Hietanen et al.
Subjective feelings—ranging from emotions and thoughts to bodily sensations and illnesses—can be mapped in a structured space. Over 1,000 participants rated 100 feelings on basic dimensions, judged their similarity, and drew where on the body each feeling was sensed. Neural similarity data from nearly 10,000 brain-imaging studies were also used. All feelings were emotionally valenced, and the intensity of bodily sensations matched the intensity of mental experiences. Five clusters emerged: positive emotions, negative emotions, cognitive processes, somatic states and illnesses, and homeostatic states. The feeling space was best explained by emotional valence, mental experiences, and bodily sensations, showing that feelings are categorical, emotional, and embodied.
Proceedings of the National Academy of Sciences of the United States of America
October 15, 2015
Masafumi Oizumi, Naotsugu Tsuchiya, S. Amari
A unified framework based on information geometry quantifies multiple causal influences among elements in a system. The proposed measure, geometrical integrated information, projects the system's probability distribution onto a constrained manifold to avoid overestimation and noncausal confounding that plague part-based approaches. It provides intuitive geometric interpretations harmonizing mutual information, transfer entropy, stochastic interaction, and integrated information, each characterized by how causal influences are disconnected. Inspired by consciousness studies of neural integration, the framework should have general utility for analyzing causal relationships in complex systems across physics and biology.
Proceedings of the National Academy of Sciences of the United States of America
April 21, 2015
Aaron Schurger, Ioannis Sarigiannidis, Lionel Naccache et al.
Conscious perception may involve the transient stabilization of distributed cortical networks, corresponding to a global brain-scale decision. Pattern-similarity analyses of MEG/EEG data from participants viewing threshold-level visual stimuli showed a decrease in variability across trials after stimulus onset, followed by a divergence in variability based on subjective report (seen/unseen), with seen trials exhibiting less variability. Within-trial stability alone could classify individual trials as seen or unseen. In patients with disorders of consciousness exposed to auditory stimuli, stability metrics diverged according to clinically diagnosed level of consciousness. Differences in signal strength could not account for these results.
Proceedings of the National Academy of Sciences of the United States of America
March 25, 2014
Loretxu Bergouignan, Lars Nyberg, H Henrik Ehrsson
Episodic memory—the ability to recall personal experiences—depends on experiencing the world from the vantage point of one's own body. When an out-of-body illusion displaced participants' sense of bodily self away from their real body during a social interaction, their later recall of those events was worse compared to when the bodily self remained aligned with the real body. Brain imaging linked this memory impairment to altered activity in the posterior hippocampus. The findings indicate that a first-person, body-centered perspective is necessary for efficient hippocampus-based encoding of real-life events, with implications for understanding memory deficits in psychiatric disorders involving dissociation.
Proceedings of the National Academy of Sciences of the United States of America
August 27, 2013
Jimo Borjigin, UnCheol Lee, Tiecheng Liu et al.
During cardiac arrest, the mammalian brain can generate a transient surge of highly coherent gamma oscillations that exceed levels seen during conscious waking. In rats undergoing experimental cardiac arrest, continuous electroencephalography revealed a global increase in gamma power, coherence, and directed connectivity within the first 30 seconds after arrest, before the electroencephalogram became isoelectric. These gamma waves were tightly phase-coupled to theta and alpha waves. The findings suggest that near-death, the brain can paradoxically produce neural correlates of heightened conscious processing.
Proceedings of the National Academy of Sciences of the United States of America
June 18, 2013
John R Searle
A satisfactory theory of consciousness remains elusive because both dualism and materialism wrongly exclude consciousness from the physical world. Consciousness consists of feeling, sentience, or awareness with five essential features: qualitativeness, ontological subjectivity, a unified conscious field, intentionality, and intentional causation. All conscious states are caused by lower-level neurobiological processes in the brain and are realized as higher-level brain features. Efforts to explain how brain processes cause consciousness have been disappointing. The unified conscious field gives organisms vastly increased power, and consciousness is necessary for higher functions of human and animal life.
Proceedings of the National Academy of Sciences of the United States of America
June 18, 2013
Ho Ming Chow, Silvina G. Horovitz, Walter S. Carr et al.
REM sleep is a distinct state of consciousness with brain activity levels similar to wakefulness but radically different conscious awareness. Using fMRI, researchers observed that the default mode network (DMN), which reflects level of consciousness, becomes functionally uncoupled during deep sleep but recouples during REM sleep, resembling wakefulness. Unlike deep sleep or wakefulness, REM shows widespread, temporally dynamic interactions between unimodal sensorimotor areas and higher-order association cortices, including the DMN. These two systems become anticorrelated and fluctuate rhythmically in alternating multisecond epochs at 0.1 to 0.01 Hz, suggesting a model relevant to dream formation and memory consolidation.
Proceedings of the National Academy of Sciences of the United States of America
June 26, 2012
Yi-Yuan Tang, Qilin Lu, Ming Fan et al.
Training in a form of mindfulness meditation called integrative body-mind training (IBMT) improved white matter efficiency in brain areas near the anterior cingulate cortex after four weeks, more than relaxation training. The improvement was shown by increased fractional anisotropy (FA) and decreases in both radial diffusivity (RD) and axial diffusivity (AD), suggesting changes in myelin and other axonal properties. After two weeks of IBMT, only AD decreased, with no change in RD or FA, though mood improved. These results demonstrate a time-course for white matter neuroplasticity from short-term meditation, which could inform interventions for mental disorders.
Proceedings of the National Academy of Sciences of the United States of America
February 23, 2010
Michel Magnin, Marc Rey, Hélène Bastuji et al.
Thalamic deactivation at sleep onset typically precedes cortical deactivation by several minutes, while reactivation during awakening is synchronized. Delays vary between subjects for similar cortical regions, and cortical activity heterogeneity during sleep onset is greater than previously thought. Asynchronous thalamo-cortical deactivation may explain hypnagogic hallucinations and the common overestimation of time needed to fall asleep.
Proceedings of the National Academy of Sciences of the United States of America
December 9, 2003
Gary Egan, Tim Silk, Frank Zamarripa et al.
Thirst was induced in humans by intravenous infusion of hypertonic saline. PET imaging revealed blood flow changes in ancient brain regions similar to those seen when thirst is maximal, while fMRI additionally showed activation in the anterior wall of the third ventricle, a region central to thirst generation in animals. Strong fMRI activations also appeared in the anterior cingulate, parahippocampal gyrus, frontal gyri, insula, and cerebellum. Drinking water to satiation immediately reduced thirst and caused a sharp decline in anterior cingulate activation, but the third ventricle activation remained unchanged, consistent with the time needed for plasma sodium to change after water absorption.