Biology subjects

Costi, S.

Publications and source records attributed to Costi, S..

5 recordsLinked to original sources

bioRxiv2026

Context-dependent effects of ketamine on emotional evidence integration

Understanding others' emotions requires continuously integrating noisy affective information as emotional states change over time. Research on emotion processing, however, has thus far focused on static environments or discrete events. Here, we developed a continuous emotional evidence integration task in which participants had to track the average emotional state in a rapidly changing sequence of faces under different levels of environmental volatility. This allowed us to examine emotion integration in changing environments. In online (n=92) and in-person (n=29) cohorts, participants integrated emotional information over longer timescales in stable environments while relying more strongly on recent evidence under volatility, consistent with principles established in perceptual decision-making. We further examined whether this process was modulated by ketamine, an NMDA receptor antagonist associated with evidence integration in the perceptual domain. We conducted a double-blind, placebo-controlled, within-subject study and probed emotion integration during the post-acute period, approximately 1.5 hours after the infusion. Ketamine modulated the temporal weighting of emotional evidence, shifting the balance between recent and past information depending on environmental volatility. Together, these findings show that emotional evidence integration dynamically adapts to the statistical structure of the environment and that ketamine can further modulate this process, which may have relevance for affective disorders.

neuroscience↗

bioRxiv2026

Ketamine attenuates habenula activity in response to aversive outcomes during Pavlovian learning

Ketamine is an NMDA receptor antagonist with rapid-antidepressant properties when administered at a sub-anesthetic dose. Preclinical models indicate that a direct injection of ketamine into lateral habenula (Hb), a small midbrain structure with an evolutionarily preserved role in aversive learning across mammals, can rapidly relieve depression-like behavior. However, there is limited evidence to explain how ketamine acts on the function of the human habenula. In a translational computational neuroscience study, 70 healthy adult volunteers were randomised in a 1:1 ratio to receive ketamine or placebo (NaCl 0.9%). We used an aversive Pavlovian conditioning paradigm combined with 7-Tesla functional neuroimaging to show that ketamine attenuates habenula response during aversive stimuli expectations and outcomes 24 hours post-infusion. We further present preliminary evidence suggesting that when aversive learning occurs after ketamine infusion, reduced habenula activity during the learning process may lead to downstream effects that diminish the aversive impact of negative affective memories. These findings provide translational support for preclinical models of ketamines mechanisms in humans.

neuroscience↗

bioRxiv2025

The renin angiotensin system in cognitive flexibility: Effects of single-dose losartan on task-switching in healthy volunteers

IntroductionCognitive flexibility, defined as the ability to shift mental strategies when environmental demands change, may influence psychological well-being and psychiatric treatment outcomes. Emerging research increasingly implicates the renin angiotensin system (RAS) in cognition, yet its role in cognitive flexibility is inadequately understood. MethodsWe conducted a double-masked trial with N=60 healthy adults aged 18-50. Participants were randomly assigned to receive a single 50 mg dose of losartan, an angiotensin II receptor blocker, or placebo. Following a waiting period, participants completed a task-switching paradigm as a measure of cognitive flexibility, which required dynamically categorizing arrows based on location or direction. Statistical analyses were conducted to determine group (losartan vs. placebo), task (location vs. direction), and switch (switching vs. repeating a task) effects on reaction time (RT) and accuracy independently. A composite bin score was also computed, integrating both RT and accuracy data. ResultsAll participants displayed the expected switch costs. While participants on losartan exhibited numerically superior RTs and accuracy, losartan did not significantly improve task-switching performance relative to placebo. This was confirmed by the bin score analysis, which indicated no benefit of losartan when RT and accuracy were considered together. An exploratory probe suggested that losartan improved accuracy on direction switch trials, indicating a potential drug effect under specific cognitive conditions. ConclusionOverall, we found no significant benefits of losartan on task-switching in healthy adults. Our results may be explained by ceiling effects in our sample, which could have hindered the detection of group differences, or possibly reflect a negligible role for the RAS in cognitive flexibility.

neuroscience↗

bioRxiv2022

Social stress induces autoimmune responses against the brain to promote stress susceptibility

Clinical studies have revealed a high comorbidity between autoimmune and psychiatric disorders, including major depressive disorder (MDD). However, the mechanisms connecting autoimmunity and depression remain unclear. Here, we aim to identify the processes linking adaptive immune abnormalities and depression. To examine this relationship, we analyzed antibody responses and autoimmunity in the chronic social defeat stress (CSDS) model in mice, and in clinical samples from patients with MDD. We show that socially stressed mice have elevated serum antibody concentrations. Activation of social stress-induced antibody responses were confirmed by detecting expansion of specific T and B cell populations particularly in the cervical lymph nodes, where brain-derived antigens are preferentially delivered. IgG antibody concentrations in the brain were significantly higher in stress-susceptible mice than in unstressed mice, and positively correlated with social avoidance. IgG antibodies accumulated around the blood vessels in brain sections from stress-susceptible mice. Moreover, sera from stress-susceptible mice exhibited high reactivity against brain tissue, and brain-reactive IgG antibody levels positively correlated with depression-like behavior. Similarly, in humans, increased peripheral levels of brain-reactive IgG antibodies were associated with increased anhedonia. Furthermore, high stress-resilience was observed in B cell-depleted mice, confirming a causal link between antibody-producing cells and depression-like behavior. This study provides novel mechanistic insights connecting stress-induced autoimmune reactions against the brain and stress susceptibility. Therapeutic strategies targeting autoimmune responses can therefore be devised to treat patients with MDD featuring immune abnormalities.

immunology↗

bioRxiv2018

Ultra-high field MRI reveals mood-related circuit disturbances in depression: A systematic comparison between 3-Tesla and 7-Tesla

Ultra-high field 7-Tesla (7T) MRI has the potential to advance our understanding of neuropsychiatric disorders, including major depressive disorder (MDD). To date, few studies have quantified the advantage of resting state functional MRI (fMRI) at 7T compared to 3-Tesla (3T). We conducted a series of experiments that demonstrate the improvement in temporal signal-to-noise ratio (TSNR) of a multi-echo fMRI protocol with ultra-high field 7T, compared to 3T MRI in healthy controls (HC). We also directly tested the enhancement in ultra-high field 7T fMRI signal power by examining the ventral tegmental area (VTA), a small midbrain structure that is critical to the expected neuropathology of MDD but difficult to discern with standard 3T MRI. We demonstrate 200-300% improvement in TSNR and resting state functional connectivity coefficients provided by ultra-high field 7T fMRI compared to 3T, indicating enhanced power for detection of functional neural architecture. A multi-echo based acquisition protocol and signal denoising pipeline afforded greater gain in signal power at ultra-high field compared to classic acquisition and denoising pipelines. Furthermore, ultra-high field fMRI revealed mood-related neuro-circuit disturbances in patients with MDD compared to HC, which were not detectable with 3T fMRI. Ultra-high field 7T fMRI may provide an effective tool for studying functional neural architecture relevant to MDD and other neuropsychiatric disorders.

neuroscience↗