Neuroscience
July 1, 1993
E O'Hearn, M E Molliver
220 citations
The psychoactive compounds ibogaine and harmaline, both beta-carboline derivatives known to cause hallucinations and tremor, can damage specific neurons in the cerebellum. In rats, a single treatment with either drug led to the degeneration of Purkinje cells in narrow, striped regions of the cerebellar vermis, as shown by loss of specific neuronal proteins and silver staining of dying cells. The damage was confined to parasagittal stripes, matching the organization of climbing fiber inputs from the inferior olive. The authors conclude that both drugs have selective neurotoxic effects on Purkinje cells and suggest that sustained activation of inferior olivary neurons may cause excitotoxic degeneration via release of an excitatory amino acid from climbing fiber terminals.
Neuroscience
February 4, 2020
Rocío Martínez Vivot, Carla Pallavicini, Federico Zamberlán et al.
116 citations
Long-term meditation practice can increase the entropy of brain oscillations, indicating a more flexible and diverse neural state. Among three traditions—focused attention (Himalayan Yoga), open monitoring (Vipassana), and open awareness (Isha Shoonya Yoga)—Vipassana produced the largest entropy increases, especially in alpha and gamma bands. All traditions increased global coherence in the gamma band while reducing metastability, stabilizing gamma dynamics. Machine learning classifiers distinguished between traditions based on gamma entropy scalp distributions. These findings show that meditation can endogenously induce high-entropy brain states, similar to those seen with serotonergic psychedelics, but achieved through prolonged practice.
Neuroscience
January 5, 2012
77 citations
No Summary
Neuroscience
August 10, 2021
Tadashi Isa, Masatoshi Yoshida
24 citations
Damage to the primary visual cortex (V1) eliminates visual awareness but some patients retain visuomotor abilities, a condition called blindsight. Studies in macaque monkeys with unilateral V1 lesions show that recovery of visually guided saccades to the affected field takes several weeks. The neural pathway from the superior colliculus to the pulvinar, along with the lateral geniculate nucleus, supports visuomotor processing, and both sides of the lateral intraparietal cortex become critical for saccade control. Signal detection analysis reveals reduced sensitivity to visual targets, indicating impaired awareness.
Neuroscience
January 1, 2004
E O'Hearn, M E Molliver
16 citations
Ibogaine, a tremorigenic hallucinogen proposed for treating addiction, causes degeneration of Purkinje cells in the cerebellum, primarily in the vermis. Previous work suggested ibogaine itself is not directly toxic; instead, it excites inferior olivary neurons, leading to excessive glutamate release and excitotoxic injury. Testing whether the non-NMDA receptor antagonist GYKI-52466 could protect against this injury, rats received ibogaine plus GYKI-52466. The antagonist did not protect at the doses used; instead, co-administration increased toxicity, causing more extensive Purkinje cell degeneration. The reasons are unclear, but the findings indicate that glutamate antagonists can worsen excitotoxic injury under some conditions, urging caution in clinical use and highlighting the complexity of glutamate receptor contributions to neuronal damage.
Neuroscience
February 16, 2025
Xinxu Ma, Shanshan Xue, Hongzhe Ma et al.
12 citations
A single dose of esketamine alleviates depressive-like behaviors in adolescent male mice exposed to the inflammatory agent LPS. The antidepressant effect is linked to increased expression of the Nrf2 protein and reduced levels of inflammatory cytokines (TNF-α, IL-1β, iNOS) in the brain's prefrontal cortex and hippocampus. Blocking Nrf2 with the inhibitor ML385 reversed both the behavioral and anti-inflammatory effects of esketamine. In the blood, esketamine also reduced pro-inflammatory and increased anti-inflammatory cytokines, an effect again blocked by Nrf2 inhibition. The findings suggest esketamine's rapid antidepressant action may work through activating Nrf2-mediated anti-inflammatory signaling.
Neuroscience
February 16, 2024
Douglas Funk, Joseph Araujo, Malik Slassi et al.
11 citations
Psilocybin increased Fos protein expression dose-dependently in the frontal cortex, nucleus accumbens, central and basolateral amygdala, and locus coeruleus of male rats, with the strongest effect in the central amygdala. Fos was expressed in both neurons and oligodendrocytes. The central amygdala, a region critical for emotional processing and learning, may be a key site where psilocybin initiates brain activation leading to neuroplastic changes underlying its therapeutic effects.
Neuroscience
February 6, 2025
Carolina Echeverry, Mariana Pazos, Maximiliano Torres-Pérez et al.
9 citations
Neurodegenerative diseases, whose main risk factor is age, are increasing worldwide as life expectancy rises. Although causes remain unknown in about 90% of cases, oxidative stress, mitochondrial dysfunction, altered proteostasis, and inflammation are key contributors to neuronal death. No cure exists; current therapies only relieve symptoms. This review examines three plant-derived compounds with neuroprotective potential used in folk medicine: quercetin (QCT), cannabidiol (CBD), and N,N-dimethyltryptamine (DMT). Each acts through distinct mechanisms—QCT as an antioxidant, CBD as an anti-inflammatory, and DMT as a promoter of neuroplasticity. The authors suggest that combining these compounds or targeting different disease stages could yield effective treatments.
Neuroscience
May 7, 2025
Murilo Barboza Fontoura, Jessica Leandra Oliveira da Rosa, Domenika Rubert Rossato et al.
3 citations
Repeated or daily doses of esketamine, the S-isomer of ketamine, prevented the reestablishment of morphine-conditioned place preference in rats, suggesting it may reduce relapse risk in opioid addiction. Rats received esketamine either every five days (acute) or daily (sub-chronic) during the extinction phase of morphine conditioning. After ten days, re-exposure to morphine did not reinstate the conditioned preference in either esketamine group. This is the first experimental evidence that esketamine could be a promising treatment for opioid use disorder, though clinical studies in humans are needed.
Neuroscience
November 1, 2024
Veronika Pohořalá, Martin Kuchař, Rainer Spanagel et al.
3 citations
Psilocybin administered immediately after extinction training did not reduce cue-induced cocaine-seeking in male and female mice or rats. In mice (16 female, 19 male) and rats (24 female, 23 male) that had learned to self-administer cocaine, psilocybin injections (1.0 mg/kg in mice; 1.0 or 2.5 mg/kg in rats) following extinction trials failed to attenuate reinstatement of drug-seeking when cues were presented. Both species and sexes showed significant cue-induced reinstatement regardless of psilocybin treatment. The findings indicate that psilocybin, at the doses and regimen tested, is ineffective in altering cocaine-seeking behavior in these animal models, leaving open whether other conditions might prove useful.
Neuroscience
May 14, 2024
Muwang Ye, Anhui Wang, Haiyang Liang et al.
3 citations
Late positivity (LP) in EEG recordings, often considered a neural correlate of consciousness, may instead reflect post-perceptual processing tied to subjective reports. In an experiment, participants completed two reporting tasks: one requiring reports on 25% of trials (low-frequency) and another requiring reports on every trial (high-frequency). Hit rates were lower and false alarm rates higher in the low-frequency task. Visual awareness negativity (VAN) was larger on reporting trials in the low-frequency task, while LP was larger on reporting trials in the high-frequency task. These results indicate that LP amplitude increases with greater task relevance and frequency of subjective reports, suggesting LP correlates with subjective reporting rather than consciousness itself.
Neuroscience
July 8, 2025
Xiang Liu, Yumeng Liu, Jun Tu et al.
2 citations
In 29 patients with major depressive disorder, six intravenous infusions of esketamine led to significant reductions in depression, anxiety, and suicidal ideation scores, along with improved cognitive scores. After two weeks, functional connectivity between the right caudal hippocampus and the left cerebellum, precuneus, and middle temporal gyrus increased. The connectivity between the right caudal hippocampus and left middle temporal gyrus negatively correlated with cognitive scores. The altered hippocampal connectivity may reflect esketamine's regulatory mechanism on depressive symptoms, involving the default network and cortico-cerebellar loop.
Neuroscience
April 6, 2025
Chandan Srivastava, Jamie A O'Reilly, Rashmi Gupta
2 citations
Long-term focused attention meditation may improve attentional control, but its effects on mismatch negativity (MMN)—a neural marker of involuntary attention shifts to unexpected sounds—remain unclear. Previous studies mixed short- and long-term meditation effects and mostly examined breath-based meditation. This study tested mantra meditation practitioners and novices using an intensity oddball paradigm, which assesses whether MMN reflects higher-order cognitive processes or sensory adaptation. Experts and novices showed similar MMN amplitude, suggesting MMN may be insensitive to meditation expertise or that novices' attentional skills also influence it. A unidirectional polarity shift in event-related potentials to deviant stimuli indicates meditation effects on MMN likely relate to higher-order deviance detection.
Neuroscience
October 5, 2025
Jannik Nicklas Eliasen, Amir Rezagholizadeh, Helene Påbøl Jacobsen et al.
1 citation
Ibogaine, a psychedelic alkaloid from root bark, shows potential for treating depression and substance use disorder, but its cellular effects are unclear. In this study, ibogaine (100 µM) was applied to putative GABAergic neurons in the ventral tegmental area (VTA) from male and female mice. No effects were observed on membrane currents, membrane potential, or spontaneous excitatory postsynaptic currents in either sex. However, ibogaine increased intracellular calcium in both sexes, decreased action potential firing rate in males only, and altered afterhyperpolarization kinetics in females only. At baseline, male VTA neurons fired at higher frequencies than female ones. These sex-differentiated effects may contribute to ibogaine's therapeutic actions.
Neuroscience
July 3, 2026
Alexis Demas
Contemporary neuroscience and psychology increasingly view perception as an active inferential process, where sensory experience arises from internally generated hypotheses shaped by prediction and uncertainty. Plato's allegory of the cave, which suggests humans mistake mediated appearances for reality, offers an early intuition of this idea. This Perspective argues that medicine, especially neurology and psychiatry, benefits from an explicit understanding of how the brain constructs subjective reality. Symptoms like hallucinations can be reframed as alterations in reality construction rather than isolated perceptual errors, complementing existing diagnostic frameworks. The paper proposes that clarifying how reality is built can enrich clinical reasoning, improve dialogue with patients, and guide research linking subcortical gating, cortical priors, and symptom phenomenology.
Neuroscience
April 6, 2026
Fernando Minauro-Sanmiguel, Hector Vargas-Perez
Mitochondrial dysfunction is a key driver of Alzheimer's disease, fueling neuroinflammation, synaptic failure, and energy collapse. Emerging preclinical evidence suggests that classic hallucinogens like psilocybin, LSD, DMT, and mescaline may restore mitochondrial integrity by activating serotonin 2A and sigma-1 receptors. In experimental models, these pathways enhance mitochondrial biogenesis, reduce oxidative stress, and preserve ER-mitochondrial coupling. DMT and 5-MeO-DMT specifically engage sigma-1 receptors at mitochondria-associated membranes, improving calcium homeostasis and cellular resilience. However, evidence for clinical efficacy in Alzheimer's remains limited and largely preclinical. This framework is presented as a hypothesis-generating model, emphasizing that neuropsychiatric safety, patient selection, and translational feasibility must be carefully addressed.
Neuroscience
March 23, 2026
Inhibitory signaling in the prefrontal cortex matures during adolescence, a critical period when parvalbumin-positive interneurons are surrounded by perineuronal nets. The endocannabinoid system helps regulate excitatory-inhibitory balance. Treating male and female rats with the synthetic cannabinoid WIN 55,212-2 from postnatal day 35 to 45 reduced perineuronal nets and delayed the emergence of parvalbumin-positive cells. These changes occurred earlier in females but persisted into adulthood in males, causing disinhibition of prefrontal cortex neural activity in awake adult animals, more strongly in males. Cannabinoid exposure during adolescence may alter perineuronal net development, leading to lasting functional changes in inhibitory signaling and potentially impairing executive control of behavior.
Neuroscience
January 22, 2026
Guilherme Lodetti, Gislaine Zilli Réus, Eduardo Pacheco Rico
Fewer than half of patients with major depressive disorder achieve remission with standard pharmacotherapy, and many cannot tolerate it. This narrative review examines classic psychedelics as an alternative treatment. These substances primarily bind to 5-HT2A receptors, increasing connectivity between sensory and motor brain networks. They generate long-term behavioral responses comparable to traditional antidepressants. Clinical and experimental studies show that classic psychedelics alleviate depressive symptoms. The mood improvement is thought to stem from effects on neuroplasticity, including neurogenesis and related signaling pathways.
Neuroscience
March 5, 2025
Hanyu Liu, Siqi Yang, Qi Zhang et al.
Opioid-induced hyperalgesia (OIH) is a complication of pain treatment where opioids paradoxically increase pain sensitivity. Using a mouse model, about 60% of mice developed OIH after three days of morphine, shown by abnormal movement and anxiety-like behaviors. Mice whose gut microbiota were eliminated with antibiotics did not develop hyperalgesia, but those receiving fecal transplants from OIH mice did. S-ketamine, but not R-ketamine, prevented OIH. Gut microbiota analysis revealed increased Enterobacteriaceae in OIH-susceptible mice, which decreased after S-ketamine treatment. The findings suggest S-ketamine alleviates morphine-induced OIH by reducing gut Enterobacteriaceae levels.
Neuroscience
November 1, 2024
Vishal Bharmauria, Hamidreza Ramezanpour, Afef Ouelhazi et al.
Ketamine alters neural activity by modulating firing rates, tuning, oscillations, and modularity while promoting hypersynchrony and random connectivity between neurons. Topical application to the visual cortex reduces firing variability and increases connectivity. A dendritic model of these changes suggests potential for focused modulation of cortical networks in clinical settings. The authors call for more animal experiments to translate these findings into therapies combining ketamine with training or adaptation. Investigating ketamine's systemic effects may deepen understanding of cognition and consciousness and advance treatments for neuropsychiatric disorders.