Science Advances
February 1, 2019
Athena Demertzi, Enzo Tagliazucchi, Stanislas Dehaene et al.
545 citations
Consciousness depends on the brain's ability to sustain rich, dynamic patterns of signal coordination. Using functional magnetic resonance imaging, a complex pattern of coordinated and anticoordinated signals characterized healthy individuals and minimally conscious patients. Unresponsive patients showed low interareal phase coherence mainly mediated by structural connectivity, with fewer transitions between patterns. This complex pattern was also seen in patients with covert cognition who could perform mental imagery tasks, validating its link to consciousness. Anesthesia increased the probability of the less complex pattern to levels seen in unresponsive patients, confirming its role in unconsciousness. These results establish generalizable fingerprints of conscious and unconscious states after brain damage.
Science Advances
November 17, 2021
Marcus W. Meinhardt, Simone Pfarr, Grégory Fouquet et al.
92 citations
Psilocybin restores deficits in the metabotropic glutamate receptor 2 (mGluR2) caused by alcohol, which leads to the reversal of pathological behaviors associated with alcoholism.
Science Advances
May 20, 2022
Tammi R. A. Kral, Kaley Davis, Cole Korponay et al.
67 citations
A large, rigorously controlled study failed to find evidence that an 8-week mindfulness-based stress reduction (MBSR) course changes brain structure. Combining data from two randomized controlled trials with 218 meditation-naïve participants, the study compared MBSR to an active control and a waitlist group. Using structural MRI scans before and after the intervention, researchers assessed gray matter volume, gray matter density, and cortical thickness. No neuroplastic changes were observed in the MBSR group compared to either control group, either across the whole brain or in regions previously reported to change. This contradicts widely referenced earlier claims that MBSR alters brain structure.
Science Advances
June 14, 2023
Leor Roseman, Christopher Timmermann, Daniel Golkowski et al.
65 citations
The effects of mind-altering drugs on brain function arise from complex interactions with multiple neurotransmitter systems, not just one. By linking the distribution of 19 neurotransmitter receptors and transporters (measured with PET) to changes in functional connectivity (measured with fMRI) caused by 10 drugs—anesthetics (propofol, sevoflurane, ketamine), psychedelics (LSD, psilocybin, DMT, ayahuasca), and others (MDMA, modafinil, methylphenidate)—the work shows a many-to-many mapping between drug effects and neurotransmitter systems. The drugs' impacts follow hierarchical gradients of brain structure and function, and regional susceptibility to drug-induced changes mirrors susceptibility to structural alterations from brain disorders.
Science Advances
October 14, 2022
Eric L Garland, Adam W. Hanley, Justin Hudak et al.
39 citations
Theta oscillations (4 to 8 Hz) in frontal midline brain regions, which support self-regulation, are inversely linked to default mode network activity involved in self-referential processing. Addiction involves impaired self-regulation and default mode network dysfunction. In a mechanistic study of 165 long-term opioid users, Mindfulness-Oriented Recovery Enhancement increased frontal midline theta during meditation compared to supportive psychotherapy. Theta during meditation was associated with self-transcendent experiences such as ego dissolution and bliss. Increased theta mediated the treatment's effect on reducing opioid misuse, suggesting mindfulness-induced theta stimulation may reset default mode network dysfunction to inhibit addictive behavior.
Science Advances
April 26, 2024
Ben Rein, Kendall Raymond, Cali Boustani et al.
37 citations
MDMA, a psychoactive drug known for its prosocial effects, enhances empathy-like behaviors in mice by increasing serotonin signaling in the nucleus accumbens. The drug, whether given systemically or infused directly into this brain region, strengthens the social transfer of pain and analgesia, a behavioral test of empathy. Optogenetically stimulating serotonin release in the nucleus accumbens mimics MDMA's effects, confirming serotonin's role. MDMA also restores deficits in empathy-like behaviors in a mouse model of autism lacking the Shank3 gene. The findings indicate that serotonin signaling in the nucleus accumbens is a core mechanism underlying MDMA's empathogenic effects.
Science Advances
August 15, 2025
Marcell J László, Judit P Vigh, Anna E Kocsis et al.
9 citations
In a rat stroke model, DMT reduces brain damage by decreasing swelling, restoring the blood-brain barrier, and shifting the body toward an anti-inflammatory state. DMT also suppresses inflammatory signals from brain and immune cells via the sigma-1 receptor. These effects suggest DMT could complement existing stroke therapies.
Science Advances
July 11, 2025
Lujuan He, Xuenan Wang, Shilin Luo et al.
8 citations
Arketamine, the (R)-enantiomer of ketamine, produces faster and longer-lasting antidepressant-like effects than esketamine in mice subjected to chronic social defeat stress. Activating the proteins CREB and MeCP2 drives the production of brain-derived neurotrophic factor (BDNF) in microglia, the brain's immune cells. This microglia-derived BDNF strengthens excitatory synaptic transmission in the infralimbic region of the medial prefrontal cortex (mPFC). It also activates mPFC neurons that project to the nucleus accumbens (NAc) shell, a brain area involved in reward and mood. These mechanisms together underlie arketamine's antidepressant-like effects, highlighting the essential role of microglial BDNF in modulating this neural pathway.
Science Advances
May 1, 2026
Anisul Arefin, Jihye Kim, Manas Pratim Chakraborty et al.
1 citation
Ketamine's antidepressant effects depend on the interplay between two types of neuromodulatory receptors: TrkB and mGluR5. mGluR5 amplifies BDNF-driven signaling through TrkB, enabling synaptic potentiation, while BDNF activation of TrkB drives mGluR5 endocytosis, impairing synaptic depression. Ketamine enhances these interactions by increasing surface and postsynaptic levels of TrkB. An mGluR5 positive allosteric modulator can further boost both modes of cross-talk and enhance ketamine's effects, revealing that receptor-receptor interplay can drive therapeutic action.
Science Advances
April 1, 2026
Paula Berman, Janka Höfer, Herschel Mehlman et al.
1 citation
A biosynthetic pathway for dimethyltryptamine (DMT) was reconstructed in a plant assay, along with the full pathways of five natural psychedelics: psilocin, psilocybin, DMT, bufotenin, and 5-methoxy-DMT. Halogenated analogs of these molecules, which do not occur naturally and may have therapeutic potential for psychiatric conditions, were also engineered. By blending catalytic functions from different organisms and using rational protein design to create mutant enzymes, the production of indolethylamine components in plants became substantially more efficient. This platform enables concurrent biosynthesis and diversification of psychoactive indolethylamines.
Science Advances
May 8, 2026
Max Levinson, Alice Waitt, Katharina Duecker et al.
Transitions in conscious visual perception involve two distinct neural mechanisms: boundary fading in visual cortex, marked by increased excitability and reduced alpha-band activity indicating a shift in excitation-inhibition balance, and higher-order perceptual monitoring in motor cortex, reflected by decreased high-alpha and beta-band activity. Microsaccadic eye movements, which delay the illusion, selectively reset both processes. These findings support a hierarchical framework where visual and motor systems jointly shape changes in conscious experience.
Science Advances
April 1, 2022
E. Oyarzabal, Li-Ming Hsu, Manasmita Das et al.
Activating norepinephrine-releasing neurons in the locus coeruleus (LC) of the mouse brain alters the default mode network (DMN). Chemogenetic stimulation of these neurons decreased cerebral blood volume and glucose uptake while increasing synchronous low-frequency fMRI activity in the frontal cortices of the DMN. Fiber photometry confirmed that LC-NE activation triggered norepinephrine release, enhanced calcium-weighted neuronal spiking, and reduced cerebral blood volume in the anterior cingulate cortex. These findings indicate that LC-NE changes the typical relationship between neuronal activity and blood volume in the frontal DMN. The activation also strengthened functional connectivity within the frontal DMN, an effect mediated by reduced inputs from retrosplenial and hippocampal regions.
Science Advances
March 1, 2020
Zirui Huang, Jun Zhang, Jinsong Wu et al.
Consciousness depends on frequent access between two key brain networks: the default mode network and the dorsal attention network, which normally alternate their activity in an anticorrelated manner. A 'temporal circuit' of dynamic brain activity trajectories regulates transitions between these networks. Balanced reciprocal accessibility of brain states within this circuit characterizes consciousness, while isolation of the networks from the temporal circuit is associated with unresponsiveness from various causes. These findings advance understanding of how anticorrelated brain systems support consciousness.