Biology subjects

Muller, S. A.

Publications and source records attributed to Muller, S. A..

5 recordsLinked to original sources

bioRxiv2026

Multimodal autonomic arousal tracks dose-dependent affective dynamics during the acute effects of DMT

Serotonergic psychedelics induce altered states of consciousness characterised by profound changes in emotional experience. Although psychedelics modulate autonomic arousal, sympathetic engagement during their affective effects remains poorly characterised. We recorded cardiac, electrodermal, and respiratory activity in 19 participants following inhalation of 20 or 40 mg of freebase N,N-dimethyltryptamine (DMT) under a semi-naturalistic blinded design, alongside time-resolved retrospective phenomenological reports. DMT induced robust increases across all autonomic markers, integrated into a multimodal index that selectively tracked subjective emotional intensity. Dose-dependent divergence followed modality-specific profiles: heart rate and respiratory differences emerged within the first 2 min post-inhalation, whereas electrodermal activity diverged only during the later phase, with higher doses showing prolonged autonomic engagement. DMT thus produces a transient sympathetic activation co-varying with emotional arousal, followed by gradual disengagement accompanied by pleasantness and bliss. By combining time- and cost-effective peripheral physiological measures with time-resolved phenomenological reports, this work contributes to the objective characterisation of psychedelic-induced affective states and provides a methodological basis for future biomarker research in clinical applications.

neuroscience↗

bioRxiv2026

Decoding the phenomenology of spontaneous thought using large language-model ratings on verbal retrospective free reports

AO_SCPLOWBSTRACTC_SCPLOWSpontaneous thoughts constitute most of everyday inner experience, yet long-standing methodological challenges obscure a thorough exploration of their content and neurophysiological underpinnings. Traditional approaches relying on thought probes impose strict constraints on phenomenological reports, whereas online verbal reports disrupt the natural flow of experience while interfering neural signals with motor artifacts. Here, we designed and tested an alternative approach to assess the neural basis of spontaneous thoughts combining delayed verbal retrospective free reports (RFR) with automated phenomenological ratings generated by large language models (LLMs). Twenty-two participants performed an eyes-closed free-thinking task, providing reports that were evaluated along ten phenomenological dimensions by four state-of-the-art LLMs and a panel of human raters. Machine-learning models (ML) were then trained to decode LLM-derived ratings from EEG spectral, complexity, and connectivity features. Our analyses showed that inter-rater agreement among LLMs exceeded that of human raters whereas ML models achieved above-chance accuracy for the prediction of emotional valence. These findings provide support for the use of LLMs for a scalable phenomenological annotation of spontaneous thoughts and suggest that their affective dimensions can be decoded from concurrent EEG activity.

neuroscience↗

bioRxiv2025

A Naturalistic Study on the Combined Neural and Psychological Effects of Psilocybin and Compassion Focused Imagery

Psilocybin is a classic psychedelic drug known to alter subjective experience and elicit long-term psychological changes, enhancing cognitive flexibility and reducing rigid self-related beliefs. Combined with compassion motivational primes that involve generating mental representations of compassion, it may increase the potential for activating the care-affiliative motivational systems, linked to several important biopsychosocial processes underpinning social safeness, social connection and mental wellbeing. We investigated the synergetic effects of psilocybin and compassion imagery with self-reported questionnaires and functional resonance imaging data (fMRI) in a sample of 105 participants. Participants were primed with either attention to breathing or a short compassion focused imagery prime. We found a long-term synergetic effect of compassion imagery and psilocybin on cognitive absorption, as well as changes relative to baseline self-compassion and decentering. Based on functional interactions between attentional, executive and default mode networks, fMRI-based classifiers detected participant engagement in compassion focused imagery before psilocybin intake and distinguished compassion imagery vs. attention to breathing priming only the high dose of psilocybin. Our results support the potential for synergistic effects from combinations of psilocybin and compassion-based interventions to induce long-term psychological changes, reshaping the functional organization of large-scale brain networks. Future confirmatory studies of our exploratory analyses should be conducted to determine whether the combination of psilocybin and compassion-based practices promotes increases in caring and contemplative abilities, enhanced psychological flexibility and well-being.

neuroscience↗

bioRxiv2025

Psilocybin-induced modulation of visual salience processing

Psychedelic compounds significantly reshape conscious perception, yet the implications of these alterations for complex visual-guided behaviors remain poorly understood. We investigated how psilocybin modulates visual salience processing during natural scene perception. Twenty-three participants completed eye-tracking tasks under self-blinded low and high doses of psilocybin, in a naturalistic design with experimental conditions unknown to participants and researchers. Subjects viewed natural scenes while their gaze patterns were recorded and analyzed in relation to normative computational saliency maps generated using a deep learning model of visual attention. Results revealed increased fixation on salient image regions and reduced inter-fixation distance under the high-dose condition, suggesting heightened sensitivity to visual salience and more localized gaze behavior. The Shannon entropy of fixations on high-saliency regions indicated a more exploratory and less predictable visual scanning of the images. Complementary EEG recordings showed broadband spectral power reductions and increased Lempel-Ziv complexity, with delta power negatively correlating with salience metrics. These findings suggest psilocybin enhances bottom-up attentional control while weakening top-down modulation, consistent with theoretical models positing facilitated bottom-up information flow under the acute effect of psychedelics.

neuroscience↗

bioRxiv2024

Protective variant in PLCgamma2 mitigates Alzheimer's disease associated pathology via enhancing beneficial microglia functions

BackgroundPLC{gamma}2-P522R (phospholipase C gamma 2, proline 522 to arginine) is a protective variant that reduces the risk for late onset Alzheimers disease. Recently, it was shown to decrease {beta}-amyloid pathology in 5XFAD mouse model of AD. In this study, our goal was to investigate the protective functions of PLC{gamma}2-P522R variant in a less aggressive mouse model of AD as well as to assess the underlying mechanisms at the molecular and cellular level using mouse and human microglia models. MethodsThe effects of the protective PLC{gamma}2-P522R variant on microglia activation, AD-related {beta}-amyloid and neuronal pathologies, as well as behavioral changes were investigated in PLC{gamma}2-P522R knock-in mice crossbred with APP/PS1 AD model mice. Transcriptomic, proteomic, and functional studies were carried out in cultured and acutely isolated adult PLC{gamma}2-P522R mouse microglia to study molecular mechanisms. Finally, microglia-like cell models generated from blood and skin biopsy samples of the PLC{gamma}2-P522R variant carriers were employed to translate the key findings to human cells. ResultsOur results demonstrate that the PLC{gamma}2-P522R variant reduced brain {beta}-amyloid plaque burden of APP/PS1 mice. Simultaneously, PLC{gamma}2-P522R variant increased non-proinflammatory microglia activation and microglia clustering around {beta}-amyloid plaques, leading to reduced {beta}-amyloid plaque-associated neuronal dystrophy. In cultured mouse primary microglia, PLC{gamma}2-P522R variant decreased accumulation of large lipid droplets, reduced cell stress, and increased acute response to strong inflammatory stimuli. Transcriptomic and proteomic analyses in acutely isolated adult mouse microglia as well as in human monocyte-derived microglial cells showed that PLC{gamma}2-P522R upregulates mitochondrial fatty acid oxidation and downregulates inflammatory/interferon signaling pathways. Accordingly, PLC{gamma}2-P522R increased mitochondrial respiration in iPSC-derived microglial cells. ConclusionsTogether, these findings suggest that PLC{gamma}2-P522R variant exerts protection against AD-associated {beta}-amyloid and neuronal pathologies via enhancing microglial barrier formation around {beta}-amyloid plaques and suppressing pro-inflammatory activation. Observed changes in fatty acid metabolism and mitochondrial flexibility as well as the downregulation of genes involved in inflammatory signaling pathways suggest that these protective effects of the PLC{gamma}2-P522R variant are mediated through an anti-ageing mechanism.

neuroscience↗