Journal of Psychopharmacology
November 20, 2013
Joel Frohlich, John D Van Horn
310 citations
The glutamate hypothesis of schizophrenia, which arose from observations that NMDAR antagonists like ketamine and PCP induce schizophrenia-like symptoms, may explain negative and cognitive symptoms better than the dopamine hypothesis and even account for dopamine dysfunction itself. Ketamine primarily acts at the NMDAR, and genetic and molecular evidence points to NMDAR hypofunction in schizophrenia. This hypofunction can explain connectional and oscillatory abnormalities through weakened excitation of GABAergic interneurons and disinhibition of principal cells. Individuals with prenatal NMDAR aberrations might experience symptom onset in adolescence when synaptic pruning reduces network connectivity below a critical threshold. Ketamine challenge is useful for studying multiple aspects of acute schizophrenia.
Brain
March 6, 2021
Joel Frohlich, Daniel Toker, Martin M. Monti
204 citations
High amplitude delta waves (1–4 Hz) in EEG have long been considered a marker of unconsciousness, observed during deep sleep, anesthesia, seizures, and disorders of consciousness. However, recent studies report prominent delta activity during conscious states, including Angelman syndrome, epilepsy, propofol anesthesia with behavioral responsiveness, postoperative delirium, dreaming, and psychedelic states. Older clinical reports also describe awake, conscious patients with high amplitude delta in Rett syndrome, Lennox-Gastaut syndrome, schizophrenia, mitochondrial diseases, hepatic encephalopathy, and non-convulsive status epilepticus.
Proc Natl Acad Sci U S A
February 1, 2022
Daniel Toker, Ioannis Pappas, Janna D. Lendner et al.
148 citations
During conscious states, the cortex operates near a mathematically specific critical point called the edge-of-chaos, the boundary between stability and chaos. Applying a modified 0-1 chaos test to ECoG and MEG recordings from humans and macaques, evidence suggests that unconscious states—such as generalized seizure and anesthesia—involve a shift of low-frequency cortical oscillations away from this critical point, disrupting information processing. Psychedelic states tune these oscillations closer to the critical point, potentially increasing information richness. Analysis of clinical EEG from patients with disorders of consciousness indicates that measuring proximity to this critical point may serve as a clinical index of consciousness.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2024
Conor H Murray, Joel Frohlich, Connor J Haggarty et al.
30 citations
Neural complexity, a measure of brain signal diversity, increases after low doses of LSD (13 and 26 µg) even when volunteers do not report an altered state of consciousness. In three separate placebo-controlled experiments with 73 healthy adults, LSD dose-dependently raised neural complexity, while THC and methamphetamine did not. LSD also reduced delta and theta brain wave power, and those reductions correlated with feelings of elation. THC reduced alpha power, which was linked to altered states, and methamphetamine increased alpha power. The findings show that increased neural complexity is neither necessary nor sufficient for an altered state of consciousness, and that different drugs affect brain activity and subjective experience through distinct mechanisms.
Communications Biology
June 20, 2023
Joel Frohlich, Pedro A. M. Mediano, Francesco Bavato et al.
16 citations
Low-frequency delta-band neural activity is typically associated with loss of consciousness and cortical down states, especially when diffuse and high amplitude. However, several classes of pharmacological agents—including antiepileptic drugs, GABA B receptor activators, acetylcholine receptor blockers, and psychedelics—can produce neural activity resembling cortical down states while participants remain conscious. Among these substances safe for healthy volunteers, some may serve as valuable research tools for determining which neural activity patterns are sufficient for consciousness or its absence.
Acta paediatrica (Oslo, Norway : 1992)
February 1, 2025
Joel Frohlich, Tim Bayne
3 citations
Consciousness in infants is likely present by 5 months of age or earlier, based on a cluster of behavioral and neural markers validated in adults that can be translated to infancy. Historically, infants were operated on without anesthesia, but attitudes shifted in the 1990s toward taking consciousness seriously. Since infants cannot report experiences, no single marker suffices, so a consensus across multiple markers pointing to the same developmental period provides a convincing argument. This cluster-based approach reviews the most promising markers for early consciousness.
bioRxiv
June 11, 2021
Daniel Toker, Ioannis Pappas, Janna D. Lendner et al.
3 citations
preprint
During conscious states, the cortex's electrical activity operates near the edge-of-chaos critical point—the boundary between stability and chaos. Applying a new chaos test to ECoG and MEG recordings from humans and macaques across waking, seizure, anesthesia, and psychedelic states shows that unconsciousness shifts cortical dynamics away from this critical point, disrupting information processing. Psychedelics may enhance information-richness by tuning activity closer to this point. Analysis of EEG from patients with disorders of consciousness suggests that measuring proximity to the edge-of-chaos critical point could serve as a clinical biomarker of consciousness.
Journal of Psychedelic Studies
May 17, 2025
Daria Dikovskaya, Bhargav Srinivasa Desikan, Joel Frohlich et al.
2 citations
A preliminary investigation into altered states of consciousness (ASC) analyzed 300 narrative reports across 12 induction methods, including meditation, float tank, and several psychedelics. Most psychedelics (except LSD), along with salvia and ketamine, shared similar content with non-pharmacological methods. In qualitative analysis, most psychedelics except LSD were deemed both positive and authentic, with authenticity predicting positive sentiment across all methods. Latent themes charted a trajectory from baseline to metaphysical experience, and text-to-image AI illustrated the underlying structure. The findings suggest that some ASC induction methods, such as salvia, ketamine, or 5-MeO-DMT, may be characterized as 'mind-manifesting,' but not others like LSD, datura, or DPH.
June 10, 2026
Theo Tobel, Aidan Cone, Emily Choquette et al.
preprint
Floatation-REST, a therapy involving floating in a tank with reduced sensory input, induces altered states of consciousness in people with anxiety and depression. In a randomized trial, 75 adults who floated reported increased awareness of their heartbeat and breathing, along with feelings of oceanic boundlessness, disembodiment, and unity—a pattern called 'aquahenosis.' These effects were strongest in those who chose longer, flexible sessions. The experiential profile overlapped with those reported for psychedelics like psilocybin and ketamine, particularly in boundary dissolution. The findings suggest Floatation-REST is a non-pharmacological method for inducing specific altered states, with oceanic boundlessness mediating improvements in positive affect.
bioRxiv Preprint Server
October 25, 2023
Joel Frohlich, Ninette Simonian, Grant Hanada et al.
preprint
Stroboscopic or flicker stimulation, which induces geometric hallucinations through closed eyelids, can entrain neural activity at specific frequencies. In a large sample of over 80 participants per condition, EEG recordings showed that multimodal stimulation combining two visual strobe frequencies with binaural beats produced powerful neural entrainment at the slower strobe frequency, resembling effects of conventional non-invasive brain stimulation. This was compared to sham stimulation with very low strobe frequencies and no binaural beats, and to a control group practicing eyes-closed meditation. The findings suggest stroboscopic stimulation warrants further development as a potential therapeutic technique for psychiatric disorders.
Trends in Cognitive Sciences
October 1, 2023
Tim Bayne, Joel Frohlich, R. Cusack et al.
Evidence from studies of functional network connectivity, attention, multimodal integration, and cortical responses to global oddballs suggests that consciousness is likely present in early infancy and may even occur before birth. Recent research is beginning to provide clues about both the content and structure of infant consciousness.
bioRxiv Preprint Server
July 10, 2019
Joel Frohlich, Lynne M. Bird, John Dell’italia et al.
preprint
Children with Angelman syndrome, who are fully conscious, have brainwave patterns that look like those seen during unconsciousness, challenging theories that link consciousness to complex neural activity. However, when comparing wakefulness to sleep, the brainwaves of 35 children with Angelman syndrome show greater complexity during wakefulness, even when accounting for slow-wave activity. This supports the idea that consciousness is tied to neural complexity and warns against assuming a lack of consciousness based solely on EEG readings.