Risk preference and choice stochasticity during decisions for other people

In several contexts, such as finance and politics, people make choices that are relevant for others but irrelevant for oneself. Focusing on decision-making under risk, we compared monetary choices made for one’s own interest with choices made on behalf of an anonymous individual. Consistent with the previous literature, other-interest choices were characterized by an increased gambling propensity. We also investigated choice stochasticity, which captures how much decisions vary in similar conditions. An aspect related to choice stochasticity is how much decisions are tuned to the option values, and we found that this was higher during self-interest than during other-interest choices. This effect was observed only in individuals who reported a motivation to distribute rewards unequally, suggesting that it may (at least partially) depend on a motivation to make accurate decisions for others. Our results indicate that, during decision-making under risk, choices for other people are characterized by a decreased tuning to the values of the options, in addition to enhanced risk seeking

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

Towards mapping neuro-behavioral heterogeneity of psychedelic neurobiology in humans

Precision psychiatry aims to identify markers of inter-individual variability that allow predicting the right treatment for each patient. However, bridging the gap between molecular-level manipulations and neural systems-level functional alterations remains an unsolved problem in psychiatry. After decades of low success rates in pharmaceutical R&D for psychiatric drugs, multiple studies now point to the potential of psychedelics as a promising fast-acting and long-lasting treatment for some psychiatric symptoms. Yet, given the highly psychoactive nature of these substances, a precision medicine approach is essential to map the neural signals related to clinical efficacy in order to identify patients who can maximally benefit from this treatment. Recent studies have shown that bridging the gap between pharmacology, systems-level neural response in humans and individual experience is possible for psychedelic substances, therefore paving the way for a precision neuropsychiatric therapeutic development. Specifically, it has been shown that the integration of brain-wide PET or transcriptomic data, i.e. receptor distribution for the serotonin 2A receptor, with computational neuroimaging methods can simulate the effect of psychedelics on the human brain. These novel 'computational psychiatry' approaches allow for modeling inter-individual differences in neural as well as subjective effects of psychedelic substances. Collectively, this review provides a deep dive into psychedelic pharmaco-neuroimaging studies with a core focus on how recent computational psychiatry advances in biophysically based circuit modeling can be leveraged to predict individual responses. Finally, we emphasize the importance of human pharmacological neuroimaging for the continued precision therapeutic development of psychedelics. Keywords: computational modeling; fMRI; neuroimaging; precision psychiatry; psychedelics; serotonin

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

Background:Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown. Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over study (ClinicalTrials.gov, NCT02451072) during which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 µg po), or (iii) Ketanserin, a selective 5-HT receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps. Findings: LSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT receptor cortical gene expression in humans. Conclusion: Together, these results strongly implicate the 5-HT receptor in LSD's neuropharmacology. This study therefore pinpoints the critical role of 5-HT in LSD's mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics. Funding: Swiss National Science Foundation (SNSF, P2ZHP1_161626, KHP), the Swiss Neuromatrix Foundation (2015 - 0103, FXV), the Usona Institute (2015 - 2056, FXV), the NIH (R01MH112746, JDM; DP5OD012109, AA; R01MH108590, AA), the NIAA ( P50AA012870-16, AA & JHK), the NARSAD Independent Investigator Grant (AA), the Yale CTSA grant (UL1TR000142 Pilot Award, AA), and the Slovenian Research Agency (ARRS J7-6829 & ARRS J7-8275, GR)

Development and validation of a dynamic 48-hour in-hospital mortality risk stratification for COVID-19 in a UK teaching hospital: a retrospective cohort study.

OBJECTIVES: To develop a disease stratification model for COVID-19 that updates according to changes in a patient's condition while in hospital to facilitate patient management and resource allocation. DESIGN: In this retrospective cohort study, we adopted a landmarking approach to dynamic prediction of all-cause in-hospital mortality over the next 48 hours. We accounted for informative predictor missingness and selected predictors using penalised regression. SETTING: All data used in this study were obtained from a single UK teaching hospital. PARTICIPANTS: We developed the model using 473 consecutive patients with COVID-19 presenting to a UK hospital between 1 March 2020 and 12 September 2020; and temporally validated using data on 1119 patients presenting between 13 September 2020 and 17 March 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is all-cause in-hospital mortality within 48 hours of the prediction time. We accounted for the competing risks of discharge from hospital alive and transfer to a tertiary intensive care unit for extracorporeal membrane oxygenation. RESULTS: Our final model includes age, Clinical Frailty Scale score, heart rate, respiratory rate, oxygen saturation/fractional inspired oxygen ratio, white cell count, presence of acidosis (pH <7.35) and interleukin-6. Internal validation achieved an area under the receiver operating characteristic (AUROC) of 0.90 (95% CI 0.87 to 0.93) and temporal validation gave an AUROC of 0.86 (95% CI 0.83 to 0.88). CONCLUSIONS: Our model incorporates both static risk factors (eg, age) and evolving clinical and laboratory data, to provide a dynamic risk prediction model that adapts to both sudden and gradual changes in an individual patient's clinical condition. On successful external validation, the model has the potential to be a powerful clinical risk assessment tool. TRIAL REGISTRATION: The study is registered as 'researchregistry5464' on the Research Registry (www.researchregistry.com)

Functional brain networks reflect spatial and temporal autocorrelation

High-throughput experimental methods in neuroscience have led to an explosion of techniques for measuring complex interactions and multi-dimensional patterns. However, whether sophisticated measures of emergent phenomena can be traced back to simpler, low-dimensional statistics is largely unknown. To explore this question, we examined resting-state functional magnetic resonance imaging (rs-fMRI) data using complex topology measures from network neuroscience. Here we show that spatial and temporal autocorrelation are reliable statistics that explain numerous measures of network topology. Surrogate time series with subject-matched spatial and temporal autocorrelation capture nearly all reliable individual and regional variation in these topology measures. Network topology changes during aging are driven by spatial autocorrelation, and multiple serotonergic drugs causally induce the same topographic change in temporal autocorrelation. This reductionistic interpretation of widely used complexity measures may help link them to neurobiology

Altered social and non-social decision-making in recreational and dependent cocaine users

Background Maladaptive decision-making is assumed to be a core feature of cocaine addiction. Indeed, numerous studies have reported deficits in non-social decision-making tasks and reward-related impulsivity in dependent cocaine users. However, social decision-making has not been examined in cocaine users yet. Moreover, it is unknown if even recreational and non-dependent cocaine use is linked to decision-making deficits. Therefore, we investigated whether recreational and dependent cocaine users exhibit alterations in social and non-social decision-making. Method The performance of healthy controls (n=68), recreational cocaine users (n=68) and dependent cocaine users (n=30) in classical decision-making paradigms (Iowa Gambling Task, Delay Discounting) and in social interaction paradigms (Distribution Game, Dictator Game) was assessed. Results Decisions in the social interaction tasks of both cocaine user groups were more self-serving compared with controls as cocaine users preferred higher monetary payoffs for themselves. In the Iowa Gambling Task, only dependent cocaine users were more likely to choose disadvantageous card decks, reflecting worse decision-making. They were also more likely to choose immediate smaller rewards over larger delayed rewards in the Delay Discounting task. Conclusions Our results imply that both recreational and dependent cocaine users are more concerned with their own monetary gain when interacting with another person. Furthermore, primarily dependent cocaine users are less foresighted and more impulsive regarding immediate reward. Overall, social interaction deficits are already present in recreational users, while non-social decision-making deficits occur predominantly in dependent cocaine users. Thus, social interaction training and cognitive remediation strategies may improve treatment success and quality of life in cocaine dependenc

Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases

\ua9 The Author(s) 2025. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.BACKGROUND AND HYPOTHESIS: Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; eg, Parkinson\u27s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; eg, psilocybin and mescaline). While these conditions differ in etiology, overlapping phenomenology, and neural mechanisms suggest shared pathways. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation. STUDY DESIGN: This narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology. STUDY RESULTS: Both LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Some features in LBDs resemble those induced by SPs (eg, illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT2AR and 5-HT1AR) modulation, while in LBDs, 5-HT2A receptor upregulation correlates with increased VH, and its inhibition (eg, with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation. CONCLUSIONS: Examining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between sensory degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations

Ketamine Induces Multiple Individually Distinct Whole-Brain Functional Connectivity Signatures

BACKGROUND Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. METHODS We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. RESULTS We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. CONCLUSIONS These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. FUNDING This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016-0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 - 2056) (FXV). CLINICAL TRIAL NUMBER NCT03842800

Experimental and numerical study of pressure drop in pipes packed with large particles

This study investigates the pressure drop in horizontal pipes packed with large particles that result in small pipe-to-particle diameter ratio both experimentally and numerically. Two horizontal pipes of 0.1905 and 0.0254 m ID filled with cylindrical or spherical particles are used to collect the experimental data for single and two-phase flows. The porosity has same value for both pipes when they packed with cylindrical particles which is 0.75, however has different values when packed with spherical particles, 0.7 for the large pipe and 0.57 for the small pipe. The Roe-type Riemann solver proposed by Santim and Rosa Int J Numer Methods Fluids 80 (9), 536–568, [36] which uses the Drift-Flux model is modified aiming to predict the pressure drop in porous media through the implementation of a new source term in the system of equations. Empirical models available in the literature are used to calculate the single and two-phase flows pressure drop. The motivation is to verify the solver capability to reproduce the two-phase flow pressure drop in porous media and to compare some empirical models existing in the literature against the experimental data provided modifying some empirical coefficients when necessary.</p