PLoS ONE
June 12, 2013
Philip R. Corlett, Victoria C. Cambridge, Jennifer M. Gardner et al.
104 citations
Delusions, the persistent bizarre beliefs characteristic of psychosis, may arise from disturbances in prediction error-dependent learning. In a placebo-controlled study with 18 human subjects, ketamine—an NMDA receptor antagonist that induces aberrant prediction error signals—was administered during re-exposure to a conditioned fear stimulus. This led to stronger subsequent fear memory compared to placebo, with the degree of strengthening correlating with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signals. A partial replication in an independent sample with an appetitive learning procedure (8 subjects) supported these findings. The results suggest a link between altered prediction error, memory strength, and psychosis, potentially explaining both the emergence and persistence of delusional beliefs.
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.
bioRxiv (Cold Spring Harbor Laboratory)
August 10, 2020
Andrea I. Luppi, Jakub Vohryzek, Morten L. Kringelbach et al.
26 citations
preprint
Consciousness arises from how the brain's structural wiring shapes its dynamic activity. By decomposing resting-state fMRI data into harmonic modes of the human structural connectome, a generalizable signature of lost consciousness emerges—whether from anesthesia or brain injury—while a reversed signature characterizes psychedelic states induced by LSD or ketamine, reflecting decoupling of function from structure. This connectome harmonic approach discriminates between behaviorally indistinguishable brain-injured patients and tracks covert consciousness, linking neurobiology to conscious experience.
bioRxiv (Cold Spring Harbor Laboratory)
July 13, 2022
Andrea I. Luppi, Justine Y. Hansen, R. Adapa et al.
5 citations
preprint
Psychoactive drugs reshape brain function by engaging multiple neurotransmitter systems simultaneously. By mapping the distribution of 19 neurotransmitter receptors and transporters (via PET) and the connectivity changes caused by 10 drugs (anesthetics, psychedelics, and stimulants), the study shows that drug effects are organized along hierarchical gradients of brain structure and function. Additionally, brain regions susceptible to drug-induced changes are also vulnerable to structural alterations from brain disorders. These findings reveal systematic links between molecular neurochemistry and large-scale functional reorganization.
Proceedings of the National Academy of Sciences of the United States of America
July 23, 2021
L. R. Spindler, A. Luppi, R. Adapa et al.
A network of brain regions called the default mode network breaks down during anesthesia and after brain damage causing disorders of consciousness. The neurochemical reasons for this breakdown were unclear. Using functional MRI, researchers found that the ventral tegmental area, a dopamine-producing brainstem region, disconnects from key default mode network nodes (precuneus and posterior cingulate) during both propofol sedation and disorders of consciousness. Stronger connectivity between the ventral tegmental area and these nodes was associated with a more awake-like configuration of the default mode network. In patients with disorders of consciousness who later improved behaviorally, this connectivity increased toward healthy levels. In a separate group of traumatic brain injury patients, the drug methylphenidate significantly strengthened this connection. The findings suggest that dopamine modulation may be central to maintaining consciousness.
Scientific Reports
February 25, 2020
D. Vatansever, Manuel S. Schröter, R. Adapa et al.
Patterns of functional interactions across distributed brain regions are thought to provide a scaffold for conscious processing, with topological changes seen in loss of consciousness. Using resting-state fMRI in healthy participants at baseline and two levels of propofol-induced sedation, the study found a persistent modular brain architecture but significant reorganization of brain hubs that formed parts of a wider rich-club collective. Reduced strength of rich-club connectivity was significantly associated with poorer performance on a semantic judgment task, highlighting the importance of this higher-order topological feature for conscious cognition.
PLoS ONE
February 13, 2020
Thomas F. Varley, Michael M. Craig, R. Adapa et al.
Fractal dimension of brain activity—a measure of complexity beyond simple randomness—is lower in patients with disorders of consciousness than in healthy volunteers. Using fMRI data, fractal dimension was computed for cortical functional connectivity networks, adjacency matrices, and BOLD time-series. Healthy volunteers (n=15) had the highest fractal dimensions, followed by patients in a minimally conscious state (n=10), and patients in a vegetative state (n=8). Decreases in fractal dimension correlated with decreasing level of consciousness regardless of injury mechanism. The findings support the hypothesis that consciousness is associated with brain complexity and that fractal structures may indicate proximity to a critical point between low- and high-entropy states.
bioRxiv Preprint Server
October 1, 2019
Tf. Varley, M. Craig, R. Adapa et al.
preprint
Brain activity's fractal dimension—a measure of complexity—decreases with loss of consciousness. Healthy volunteers showed higher fractal dimension than patients in a minimally conscious state, who in turn showed higher dimension than those in a vegetative state, regardless of injury cause. Fractal dimension of functional connectivity networks, adjacency matrices, and BOLD time-series all correlated with level of consciousness. These findings support the idea that consciousness requires complex, critically organized brain activity, consistent with prior EEG, MEG, and fMRI work.