Skip to content

Frontiers in Neuroscience

39 papers in the library · 2,886 citations · publishing 2010-2026

Papers

The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells

Frontiers in Neuroscience September 14, 2016 Attila Szabó, A. Kovács, Jordi Riba et al. 18 citations

N,N-dimethyltryptamine (DMT), an endogenous hallucinogen found in the human brain, activates the sigma-1 receptor (Sig-1R), an intracellular chaperone that helps manage cellular stress. This study tested whether DMT protects brain cells from hypoxia by activating Sig-1R. In cultured human cortical neurons, macrophages, and dendritic cells exposed to severe hypoxia (0.5% O2), DMT robustly increased cell survival through Sig-1R activation. This effect was linked to decreased expression and function of hypoxia-inducible factor 1 alpha (HIF-1α), suggesting DMT alleviates hypoxic stress independently of HIF-1. The results indicate DMT may be endogenously produced during stress to protect the brain from hypoxic or ischemic damage.

Acute psilocybin increased cortical activities in rats

Frontiers in Neuroscience May 23, 2023 Junhong Liu, Yuanyuan Wang, Ke Xia et al. 17 citations

Psilocybin, the hallucinogenic compound in magic mushrooms, activates brain regions and increases functional connectivity in rats, similar to its effects in humans. Ten minutes after injection (2.0 mg/kg), positive brain activity appeared in the frontal, temporal, and parietal cortex, hippocampus, and striatum. Connectivity increased among regions including the cingulate cortex, dorsal striatum, prelimbic, and limbic areas. Psilocybin also raised levels of EGR1, a protein linked to depressive symptoms, throughout the brain, indicating widespread activation. These findings suggest the hyperactive state may underlie psilocybin's pharmacological effects.

Mindfulness meditation styles differently modulate source-level MEG microstate dynamics and complexity

Frontiers in Neuroscience February 2, 2024 Antea D’Andrea, Pierpaolo Croce, Jordan O’Byrne et al. 13 citations

Theravada Buddhist monks with extensive meditation experience underwent magnetoencephalography during focused attention meditation, open monitoring meditation, and resting states. Brain microstate coverage and occurrence differed between meditation and rest and between the two meditation styles. The Hurst exponent, a measure of long-range memory in brain dynamics, was lower during both meditation conditions than during rest. Lempel-Ziv complexity, which quantifies signal complexity, increased progressively from rest to focused attention meditation to open monitoring meditation. These changes in brain criticality indices suggest that meditation shifts brain dynamics toward a more critical state, paralleling changes in cognitive state.

Near-Death High-Frequency Hyper-Synchronization in the Rat Hippocampus

Frontiers in Neuroscience July 31, 2019 Yujiao Zhang, Zhenyi Li, J. Zhang et al. 13 citations

Near-death experiences (NDE) involve enhanced perception and memory, and have been linked to a surge in high-frequency brain oscillations. In anesthetized rats dying from an overdose of chloral hydrate, a surge in beta and gamma band power occurred in the hippocampus, with gamma power specifically tied to impending death. Theta band power was suppressed. Cardiac arrest only developed after breathing stopped and all oscillatory activity collapsed, showing that the high-frequency surge is not exclusive to cardiac arrest. The gamma synchronization in the CA1 region may contribute to NDEs that occur both with and without cardiac arrest.

Case report: Improvement in refractory functional seizures, depression, and quality of life with ketamine-assisted therapy

Frontiers in Neuroscience June 12, 2023 E. Argento, Egiroh Omene, Alexandra Jaeger et al. 10 citations

A 51-year-old woman with daily functional seizures, major depressive disorder, and posttraumatic stress disorder who had not responded to prior treatments underwent a novel protocol of ketamine-assisted therapy. After 3 weeks of therapy followed by 20 weeks of intermittent ketamine treatment and ongoing psychotherapy, her seizures were significantly reduced in frequency and severity, and she showed substantial improvements in depressive symptoms and functional ability. This first reported case suggests that ketamine-assisted therapy may help treat functional seizures, but rigorous studies are needed to confirm the findings.

Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats

Frontiers in Neuroscience June 22, 2023 Filip Tylš, Čestmír Vejmola, Vlastimil Koudelka et al. 9 citations

Psilocybin's psychoactivity is primarily attributed to agonism at 5-HT2A receptors, but it also binds to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. In an animal model, psilocin (psilocybin's active metabolite) induced broadband desynchronization and disconnection in EEG, decreasing mean absolute power across 1–25 Hz and reducing global functional connectivity, particularly fronto-temporal connections. Antagonists of 5-HT1A, 5-HT2A, and 5-HT2C receptors, as well as antipsychotics haloperidol (D2 antagonist) and clozapine (mixed D2/5-HT antagonist), normalized power decreases in 1–25 Hz, but only clozapine affected 25–40 Hz decreases. The 5-HT2A antagonist reversed psilocin-induced connectivity decreases, while other drugs had no effect, indicating that multiple serotonergic and dopaminergic mechanisms contribute to these neurophysiological changes.

What Can Neuroscience Tell Us about the Hard Problem of Consciousness?

Frontiers in Neuroscience September 7, 2016 Berit Brogaard, Dimitria Electra Gatzia 9 citations

The article argues that the concept of the self is not a static entity but a dynamic process that emerges from the interactions between brain, body, and environment. It suggests that understanding the self requires integrating insights from neuroscience, psychology, and philosophy, and that this dynamic view has implications for fields like neuroprosthetics and brain-computer interfaces. The authors propose that the self is continuously constructed through neural and bodily activity, challenging traditional notions of a fixed identity.

Cortical structural differences following repeated ayahuasca use hold molecular signatures

Frontiers in Neuroscience October 5, 2023 Pablo Mallaroni, Lilian Kloft, Natasha L. Mason et al. 8 citations

Repeated ayahuasca use is associated with a spatially distributed pattern of brain structural changes: sensorimotor areas become more distinct from surrounding regions while transmodal areas become less distinct. These changes correlate with the expression of genes for 5-HT2A receptors and other targets of ayahuasca, as well as with genes for transcription factors and immediate early genes previously linked to psychedelic-induced neuroplasticity in animal studies. The findings suggest that molecular mechanisms of psychedelic action may scale up to large-scale brain organization in living humans, potentially helping to explain behavioral differences in experienced users.

Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats

Frontiers in Neuroscience May 1, 2025 Evan Fuini, Arnold Chang, Josh Edwards et al. 6 citations

Psilocybin, a hallucinogen, produces dose-dependent increases in brain activity in awake rats, particularly in the somatosensory cortex, basal ganglia, and thalamus. Female rats showed greater activation than males at the 0.3 mg/kg dose in thalamic and basal ganglia regions. The drug also caused a global increase in functional connectivity, especially hyperconnectivity to the cerebellum. Higher doses activated circuits involved in sensory filtering and motor organization, such as the cortico-striato-thalamo-cortical circuit and claustrum. However, the direction of BOLD signal changes and neural network activity patterns differed from those reported in human studies.

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

Frontiers in Neuroscience February 7, 2024 Jennifer Warner-Schmidt, Martin Stogniew, Blake Mandell et al. 6 citations

Methylone, a monoamine uptake inhibitor and releaser currently in clinical development for PTSD, produced rapid changes in gene expression in rat brain areas linked to PTSD and major depressive disorder. In the amygdala, methylone regulated myelin-related genes; in the frontal cortex, it upregulated genes involved in neuroplasticity. Unlike MDMA, methylone showed no off-target activity at 168 tested GPCRs, including 5HT2A and 5HT2C receptors. These results suggest methylone acts as a rapid-acting neuroplastogen with higher specificity and fewer off-target effects than MDMA, supporting its potential for treating PTSD and possibly other neuropsychiatric disorders.

What fMRI studies say about the nature of the psychedelic effect: a scoping review

Frontiers in Neuroscience July 1, 2025 Michal Beneš, Tomáš Páleníček, Jiřı́ Horáček 4 citations

A scoping review of fMRI studies on serotonergic psychedelics (psilocybin, LSD, DMT) identifies unifying themes: de-differentiation centered on the default mode network, complex changes in the thalamus, amygdala, and medial temporal lobe, and the importance of ego dissolution. These findings complement established models of psychedelic action and highlight contrasts with phenomenologically similar states and links to other biological markers.

Editorial: Psychedelic-assisted psychotherapies: from clinical trials to credibility

Frontiers in Neuroscience March 23, 2026 Malkanthi Evans, Andrew Charrette

Psychedelic therapies show promise for treatment-resistant depression, PTSD, anxiety, and substance-use disorders, but significant methodological and ethical challenges remain. Issues include inadequate masking in trials, expectancy effects, and reproducibility concerns. Early-phase studies indicate rapid symptom improvement, supported by neuroimaging insights, but large multisite trials with harmonized protocols and long-term follow-up are still needed. The role of psychotherapy in psychedelic-assisted treatment is debated; some developers include only psychological support. Subjective aesthetic experiences—perceptual richness, emotional resonance, beauty—are strongly linked to emotional breakthroughs and clinical outcomes. Neuroimaging shows DMT modulates brain connectivity in socio-emotional circuits. Psilocybin promotes emotional openness and cognitive flexibility. Future research must clarify mechanisms, optimize protocols, and ensure safety and generalizability.

Acute psilocin increased cortical activity in rat

Frontiers in Neuroscience February 4, 2026 Junhong Liu, Y. Lynn Wang, Ke Xia et al.

Psilocin, the active component of magic mushrooms, increases brain activity and functional connectivity in rats, mirroring effects seen in humans. Ten minutes after injection, elevated activity was detected in the frontal, temporal, and parietal cortex (including the cingulate and retrosplenial cortex), hippocampus, and striatum. Functional connectivity analysis showed enhanced interconnectivity among the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Additionally, psilocin increased levels of the immediate early gene EGR1 in most cortical and striatal areas, indicating consistent activation. These findings suggest that psilocin induces a hyperactive state in rats, which may underlie its pharmacological effects.

The Meaning-Enhancing Properties of Psychedelics and Their Mediator Role in Psychedelic Therapy, Spirituality, and Creativity

Frontiers in Neuroscience March 6, 2018 Ido Hartogsohn

Psychedelics appear to enhance the perception of meaning, which may help explain their therapeutic, creativity-boosting, and mystical-type effects. Building on earlier work linking psychedelic-induced meaning enhancement to amplified placebo responses, this paper proposes that similar mechanisms underlie creativity enhancement and mystical experiences. The authors discuss the broader social and public-health implications and suggest directions for further research into how these meaning-amplifying properties work and how they might be harnessed.