Biology subjects

Shinozuka, K.

Publications and source records attributed to Shinozuka, K..

10 recordsLinked to original sources

bioRxiv2026

Psychedelics Restructure the Global Workspace of Consciousness

Psychoactive drugs profoundly alter consciousness, but the neural mechanisms by which they do so remain poorly understood. Global workspace theory may provide a framework for investigating these mechanisms. The global workspace, a candidate neural substrate of consciousness, is a set of brain regions that integrate and disseminate information to the rest of the brain. According to a recent model, the integrators, or 'gateways,' are characterized by synergistic interactions with other brain regions, while the disseminators, or 'broadcasters,' exhibit redundant interactions. Here, we measured the effects of various psychoactive drugs, including 'classic' psychedelics like LSD, mescaline, and psilocybin, 'atypical' psychedelics (entactogens) like MDMA, and the stimulant D-amphetamine, on the global workspace. In a secondary analysis of resting-state functional magnetic resonance imaging (fMRI) data on all these drugs, we found that classic psychedelics are associated with significant increases in the number of gateways in the frontoparietal control and dorsal attention networks. Meanwhile, MDMA and amphetamine reduced the number of gateways in the visual and somatomotor networks. The regional topographies of both synergy and redundancy distinguished classic psychedelics from other drugs. Finally, drugs producing similar changes in synergy and redundancy also produced similar profiles of subjective effects. Overall, our findings provide the first direct evidence that psychedelics may alter the synergistic and redundant interactions that characterize the global workspace of consciousness.

neuroscience↗

bioRxiv2026

Ultrasonic potentiation of ketamine neuromodulation

The psychiatric utility of ketamine is limited by its dissociative and systemic side effects. Recently, to enable precision ketamine pharmacotherapy, we introduced SonoKet, ketamine-loaded acoustically activatable liposomes that enable focused ultrasound (FUS)-targeted ketamine delivery to millimeter-sized brain regions. In initial studies, we observed that SonoKet uncaging targeted ketamine to the ultrasound-treated brain region, while inducing greater electrophysiologic and behavioral functional effects than dose-matched free ketamine. To further define these uncaging-potentiated neuromodulatory effects, we used solid-phase microextraction (SPME) coupled to LC-MS/MS to investigate the effect of ultrasound and SonoKet uncaging on key neurotransmitters in real-time. SPME probes were used to sample ketamine, its metabolites, and glutamate, GABA, serotonin (5-HT), and dopamine in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and retrosplenial cortex (RsC) of awake rats. Sampling occurred before and after intravenous administration of either SonoKet, free ketamine, or saline, with FUS targeted to either a frontolimbic or caudal brain region. FUS alone did not yield significant changes in neurotransmitter concentration, nor did it affect the pharmacodistribution of free ketamine. In contrast, FUS generally increased the neurotransmitter response to free ketamine, suggesting an ultrasonic potentiation of ketamine neuromodulation. SonoKet (0.75 mg/kg) uncaging with FUS elicited further elevations in glutamate, GABA, and 5-HT within the FUS-targeted region, along with an increase in dopamine in the NAc when the frontolimbic region was sonicated. These increases were similar to or higher than those induced by 10 mg/kg free ketamine alone or 0.75 mg/kg free ketamine combined with FUS, especially with frontolimbic SonoKet uncaging. Altogether, FUS potentiates ketamine-induced neuromodulation, with spatially specific and synergistically greater effects when ketamine is spatially localized via ultrasonic uncaging. This strategy could augment ketamine pharmacotherapy for psychiatric diseases, while limiting its dissociative and abuse liabilities. HighlightsO_LIFocused ultrasound potentiated ketamine-driven glutamate, serotonin, and dopamine release C_LIO_LILocalized ketamine delivery with SonoKet uncaging drove synergistically greater region-specific neurochemical responses C_LIO_LIUncaging boosts ketamine effects at a fraction of the ketamine dose C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/741494v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@15c75c8org.highwire.dtl.DTLVardef@138d06eorg.highwire.dtl.DTLVardef@fc0c56org.highwire.dtl.DTLVardef@18e233b_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2026

Ibogaine is associated with reorganization of high-beta brain networks in veterans with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a debilitating condition that affects millions of veterans. A recent observational study in 30 veterans showed that a single dose of the atypical psychedelic ibogaine can be highly effective at treating PTSD up to twelve months later. Although a prior study demonstrated that ibogaine transiently alters electroencephalography (EEG) power in various frequency bands, the long-term, network-level neural mechanisms targeted by ibogaine are unclear. Here, we investigated whether ibogaine-related clinical improvements are associated with the reorganization of certain brain networks. We applied a novel framework, FREQuency-resolved brain Network Estimation via Source Separation (FREQ-NESS), to identify frequency-specific brain networks in resting-state EEG data acquired at baseline, three to four days after treatment (immediate-post), and one month after ibogaine. At both the immediate-post and one month-post timepoints, high-beta (24 and 25 Hz) networks shifted away from frontal areas and towards posterior regions, an effect that was replicated in an independent EEG dataset on ibogaine treatment for opioid use disorder. This posterior shift was significantly correlated with improvements in PTSD symptoms at both timepoints. Neural field modeling demonstrated that these posterior high-beta shifts are associated with increases in corticocortical, but not corticothalamic, connectivity. Our results are consistent with prior evidence implicating aberrant frontal beta-band activity in PTSD. Overall, we demonstrate that the reconfiguration of high-beta brain networks could be a robust biomarker for ibogaines therapeutic effects.

neuroscience↗

bioRxiv2025

Neuroelectrophysiological correlates of extended cessation of consciousness in advanced meditators: A multimodal EEG and MEG study

In some contemplative traditions, "extended cessation" (EC) refers to a state of advanced meditation in which the meditator intentionally suppresses their own consciousness and re-emerges with a profound sense of clarity and equanimity. Here, we present the first electrophysiological study of EC, in which five meditators underwent concurrent electroencephalography (EEG) and magnetoencephalography (MEG) recording. EC significantly reduced alpha power. EC also tended to increase neural complexity, unlike other states in which consciousness is absent (e.g., sleep, anesthesia, disorders of consciousness). Our results indicate that the neural correlates of EC are distinct from other states that induce loss of consciousness and that complexity is not a sufficient condition for consciousness, while also providing new insights into the implications of advanced meditation for human flourishing.

neuroscience↗

bioRxiv2025

Morning sickness-like changes during pregnancy in non-human primates and rodents

Nausea and vomiting of pregnancy (NVP), commonly referred to as "morning sickness," causes a range of symptoms including nausea, vomiting, weight loss, anorexia, and malaise in pregnant women during early pregnancy. Although NVP highly affects the quality of life of pregnant women, the absence of model animals has prevented us from revealing the underlying mechanisms. Here, to identify whether non-human animals may serve as models for studying NVP, we analyzed metabolic changes during pregnancy in common marmosets and mice. Marmosets exhibited a transient weight decrease during the period of placental development in approximately 22% of pregnancies. Some marmosets repeatedly showed transient weight loss across multiple pregnancies, suggesting individual variations in the likelihood of NVP-like symptoms. Although mice did not show apparent alteration in body weight, they exhibited a slowdown in food intake and alterations in locomotor activity during the corresponding phase. These shared alterations suggest that marmosets and mice may exhibit phenomena analogous to human NVP and could serve as useful models for investigating its biological basis. HighlightsO_LIMarmosets exhibited a transient weight loss during placental development in 22% of pregnancies. C_LIO_LIThere was individual variation in how often the transient weight loss occurred in marmosets. C_LIO_LIFood intake and activity in C57BL/6 mice are altered during the corresponding gestational phase. C_LIO_LIMultiple morning sickness-like phenomena were observed in non-human mammals. C_LI

physiology↗

bioRxiv2025

LSD reconfigures the frequency-specific network landscape of the human brain

Lysergic acid diethylamide (LSD) and other psychedelic substances profoundly alter human consciousness. While several studies have demonstrated changes in brain function and connectivity associated with psychedelics, we still have a limited understanding of how LSD reshapes brain networks operating across different frequency bands. In this study, we applied the recently developed FREQ-NESS method to MEG data from 14 healthy participants who received LSD under four conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. LSD significantly restructures canonical networks in the alpha and beta bands. Relative to broadband brain activity, it enhances the prominence of high alpha (12.1, 13.3 Hz) across all experimental conditions and high beta (25.3 Hz) in three conditions. Conversely, LSD decreases the prominence of low beta (18.1, 19.3 Hz) in both Open and Closed conditions and low alpha (8.5 Hz) in the latter. In addition, LSD substantially alters the spatial distributions or topographies of the networks. Under LSD, the low alpha (8.5 Hz) network shifts anteriorly toward the motor cortex, while high alpha (12.1, 13.3 Hz) becomes more localized to the visual cortex. Low beta (18.1, 19.3 Hz) expands over the temporal and occipital cortices, whereas high beta (25.3, 26.5 Hz) topographies remain unchanged. Our findings provide critical insights into the specific frequencies and spatial networks in which LSD modulates brain connectivity, adding nuance to prevailing theories about network disintegration under psychedelics. Significance statementPsychedelic substances such as lysergic acid diethylamide (LSD) profoundly alter perception and cognition, yet their effect on brain activity across different frequency bands remains unclear. Using FREQ-NESS applied to MEG data, we show that LSD reorganizes brain networks by enhancing high-frequency alpha and beta rhythms while suppressing lower-frequency counterparts. These changes occur across various experimental conditions and shift the spatial distribution of brain activity, particularly in motor and visual regions. Our findings suggest that LSD modulates brain connectivity in a frequency- and region-specific manner, offering new insights into how psychedelics alter consciousness. This work advances our understanding of LSDs neural effects, which may be relevant for therapeutic applications and models of brain function.

neuroscience↗

bioRxiv2024

The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State

Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic that induces a profoundly altered conscious state. In conjunction with psychological support, it is currently being explored as a treatment for generalized anxiety disorder and depression. The dorsolateral prefrontal cortex (DLPFC) is a brain region that is known to be involved in mood regulation and disorders; hypofunction in the left DLPFC is associated with depression. This study investigated the role of the DLPFC in the psycho-emotional effects of LSD with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) data of healthy human participants during the acute LSD experience. In the fMRI data, we measured the correlation between changes in resting-state functional connectivity (RSFC) of the DLPFC and post-scan subjective ratings of positive mood, emotional arousal, and ego dissolution. We found significant, positive correlations between ego dissolution and functional connectivity between the left & right DLPFC, thalamus, and a higher-order visual area, the fusiform face area (FFA). Additionally, emotional arousal was significantly associated with increased connectivity between the right DLPFC, intraparietal sulcus (IPS), and the salience network (SN). A confirmational "reverse" analysis, in which the outputs of the original RSFC analysis were used as input seeds, substantiated the role of the right DLPFC and the aforementioned regions in both ego dissolution and emotional arousal. Subsequently, we measured the effects of LSD on directed functional connectivity in MEG data that was source-localized to the input and output regions of both the original and reverse analyses. The Granger causality (GC) analysis revealed that LSD increased information flow between two nodes of the ego dissolution network, the thalamus and the DLPFC, in the theta band, substantiating the hypothesis that disruptions in thalamic gating underlie the experience of ego dissolution. Overall, this multimodal study elucidates a role for the DLPFC in LSD-induced states of consciousness and sheds more light on the brain basis of ego dissolution.

neuroscience↗

bioRxiv2024

LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics

Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed functional connectivity. We measure directed functional hierarchy in a magnetoencephalography (MEG) dataset of 16 healthy human participants who were administered a psychedelic dose (75 micrograms, intravenous) of lysergic acid diethylamide (LSD) under four different conditions. LSD diminishes the asymmetry of directed connectivity when averaged across time. Additionally, we demonstrate that machine learning classifiers distinguish between LSD and placebo more accurately when trained on one of our hierarchy metrics than when trained on traditional measures of functional connectivity. Taken together, these results indicate that LSD weakens the hierarchy of directed connectivity in the brain by increasing the balance between senders and receivers of neural signals.

neuroscience↗

bioRxiv2023

The Hierarchy of Psychedelic Effects: Three Systematic Reviews and Meta-Analyses

Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: 1) subjective experience (phenomenology), 2) neuroimaging and 3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.

neuroscience↗

bioRxiv2023

Infant attachment behaviors reflect the parenting style of individual caregiver in common marmosets

Childrens physical, cognitive, and emotional maturation require adequate interactions and secure attachment with their primary caregivers. However, the causal relationships between parenting components and infant attachment behaviors remain unclear. New World monkey common marmosets provide an ideal model of human parent-infant relations because, like humans, infant attachment is shared among family caregivers, including parents and older siblings using intricate vocal communications. Combining the natural variations in parenting styles and subsecond-scale microanalyses of dyadic vocal and physical interactions, we demonstrate that marmoset infants signal their need by context-dependent call use and selectively maintain proximity with familiar caregivers. The infant attachment behaviors are individually tuned according to the caregivers parenting style; infants keep producing isolation calls when they are carried by rejecting caregivers and exhibit avoidance toward neglectful and rejecting caregivers. Family-deprived infants failed to develop such adaptive uses of attachment behaviors or age-appropriate autonomy and exhibited disorganized attachment behaviors. Thus, marmoset infants shape their ability to modulate their intricate attachment system depending on the caregivers attitude through early social interactions with their family caregivers. Demonstrating the significant similarity of the infant attachment system between marmosets and humans, these findings will pave a path to elucidating the neural mechanisms of the infant attachment system.

animal behavior and cognition↗