NeuroImage
February 15, 2021
Andrea I Luppi, Robin L Carhart-Harris, Leor Roseman et al.
186 citations
LSD alters brain network dynamics non-uniformly over time, making globally segregated connectivity states more complex and weakening the link between functional and anatomical connectivity. The drug reduces functional connectivity in the anterior medial prefrontal cortex specifically during states of high segregation. Ego dissolution was predicted by increased small-world organization during a state of high global integration. These temporally-specific effects reveal a more nuanced picture of psychedelic-induced changes in brain connectivity and complexity than previously reported.
Nature communications
October 3, 2022
S Parker Singleton, Andrea I Luppi, Robin L Carhart-Harris et al.
156 citations
Psychedelics like LSD and psilocybin temporarily alter subjective experience by acting on serotonin 2a (5-HT2a) receptors, increasing the diversity (entropy) of brain activity. This increase may arise from a flattening of the brain's control energy landscape. Using fMRI data, the authors show that these compounds reduce the control energy needed for transitions between brain states compared to placebo. Across individuals, lower control energy correlates with more frequent state transitions and higher entropy. Incorporating PET data on 5-HT2a receptor distribution under non-drug conditions, the analysis links these receptors to reduced control energy. The findings demonstrate that receptor-informed network control theory can model how neuropharmacological manipulation affects brain dynamics.
Communications biology
January 28, 2023
Andrea I Luppi, Jakub Vohryzek, Morten L Kringelbach et al.
98 citations
Consciousness depends on how tightly brain function follows the brain's physical wiring. Using MRI scans, researchers measured structure-function coupling across spatial scales in people who were unconscious from anesthesia or brain injury and in people under psychedelics (LSD or ketamine). During loss of consciousness, function more closely tracked the brain's structural connections, a signature that could distinguish behaviorally similar brain-injured patients and detect covert consciousness. In contrast, psychedelics decoupled function from structure, and this decoupling correlated with physiological and subjective scores. The findings suggest that connectome harmonic decomposition reveals how neuromodulation and network architecture jointly shape consciousness.
Nature communications
March 11, 2024
Andrea I Luppi, Lynn Uhrig, Jordy Tasserie et al.
43 citations
Loss of consciousness under anesthesia increasingly constrains brain activity to follow the brain's physical structure, collapsing hierarchical cortical organization across scales. This effect was observed with three different anesthetics—propofol, sevoflurane, and ketamine—and was reversed by electrically stimulating the central thalamus, which also restored behavioral signs of arousal. Stimulating the ventral lateral thalamus did not produce these effects, showing specificity. The findings identify distributed brain signatures of consciousness that are orchestrated by particular thalamic nuclei.
Brain
January 1, 2024
Andrea I Luppi, Manesh Girn, Fernando E Rosas et al.
25 citations
Serotonin 2A receptor (5-HT2AR) signaling drives both the evolutionary expansion and ongoing modulation of the human cerebral cortex's most complex cognitive centers. The cortex is organized along a gradient from simple sensory processing to high-level integration, with the transmodal cortex at the apex—a region disproportionately enlarged in humans and rich in 5-HT2AR expression. During early brain development, 5-HT2AR signaling on neural progenitor cells stimulates their proliferation, contributing to cortical expansion. In the adult brain, 5-HT2AR agonism promotes neuroplasticity, learning, and cognitive flexibility with therapeutic potential. The receptor thus plays a dual role in enabling cortical growth and sophisticated functioning.
Communications biology
April 18, 2025
S Parker Singleton, Christopher Timmermann, Andrea I Luppi et al.
7 citations
After DMT injection, the brain requires less control energy to transition between states compared to placebo, indicating a more flexible and less constrained brain dynamic. These energy changes track with EEG signal diversity and subjective intensity of the drug experience. The regional pattern of DMT's effects aligns with serotonin 2a receptor density, and a model using receptor distribution and pharmacokinetics can predict the drug's impact on brain energy trajectories.
British journal of anaesthesia
April 1, 2025
Milan Van Maldegem, Jakub Vohryzek, Selen Atasoy et al.
3 citations
Ketamine, at anesthetic doses, produces a state where people are unresponsive yet often report vivid inner experiences, separating conscious awareness from behavioral responsiveness. Using connectome harmonic decomposition on fMRI data, researchers found that brain signals during ketamine-induced unresponsiveness show increased fine-grained spatial patterns, indicating higher neural granularity. This harmonic signature aligned with those of LSD-induced and ketamine-induced psychedelic states, but misaligned with signatures from unconscious individuals due to propofol sedation or brain injury. The method can track changes in conscious awareness even when behavior is absent, offering a tool for consciousness and anesthesia research.
eLife
July 18, 2024
Andrea I Luppi, Pedro A M Mediano, Fernando E Rosas et al.
1 citation
Loss of consciousness significantly disrupts the brain's ability to integrate information. In a study involving functional MRI analysis, it was revealed that gateway regions in a 'synergistic global workspace' correspond to the default mode network, while broadcaster regions align with the executive control network. This integration breakdown occurs during general anaesthesia or disorders of consciousness, with recovery restoring functionality. The findings enhance understanding of consciousness by bridging Global Neuronal Workspace and Integrated Information Theory, highlighting the critical role of brain networks in maintaining conscious experience.
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
Brain communications
January 1, 2026
Dorottya Szocs, Dian Lyu, Andrea I Luppi et al.
The pulvinar nucleus of the thalamus shows the strongest functional connectivity change with loss of consciousness under anesthesia in healthy volunteers, while the ventral-latero-ventral nucleus shows the strongest change in patients with disorders of consciousness. These nuclei exhibit distinct connectivity patterns with higher-order brain networks such as the default mode and executive control networks. In patients, the neural connectivity biomarker mirrored behavioral changes, suggesting potential clinical relevance for targeted deep brain stimulation therapy.