Biology subjects

Rascu, M.

Publications and source records attributed to Rascu, M..

4 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↗

bioRxiv2025

Low-intensity focused ultrasound to human amygdala reveals a causal role in ambiguous emotion processing and alters local and network-level activity

The amygdala is a core region changed in depression, a disorder characterized by compromised emotion, motivation and learning processes. However, lesion studies in humans examining amygdala function have largely focused on its role in processing fear. It currently remains unclear what causal role the human amygdala plays in more complex emotion, motivation and learning processes in daily life. This is because it has not been possible to reversibly modulate amygdala activity non-invasively in humans. Here, we used transcranial focused ultrasound stimulation (TUS) to bilaterally perturb neural activity in the basolateral amygdala (BLA). In separate sessions (n = 87), 29 healthy volunteers received offline-TUS to bilateral BLA, mid-insula or sham before playing a novel emotional learning task validated in an independent large cohort online (n = 210). 7T-resting-state and metabolite signals clearly demonstrated target engagement. BLA-TUS reduced the BLAs connectivity fingerprint and decreased its excitation/inhibition balance, suggesting an inhibitory effect of our TUS protocol on BLA activity. In behaviour, BLA-TUS caused a stimulation volume-dependent increase in the tendency to approach neutral, emotionally ambiguous faces, treating them more similarly to happy faces, and a slowing of reaction times for those two emotion categories. These effects were functionally and regionally specific and suggest a causal role for the amygdala in resolving emotional ambiguity. Our results provide important insights for future studies into mood disorders where ambiguous situations might be harder to resolve, which could contribute to existing emotional and learning biases.

neuroscience↗

bioRxiv2025

Causal necessity of human hippocampus for structure-based inference in learning

When meeting new individuals or encountering known individuals in new circumstances, we intuitively map out their relationships - not merely by direct experience, but by quickly inferring new connections based on prior relational knowledge. Using a novel task, we demonstrated that participants indeed employ knowledge of relational structures to facilitate learning of new relationships in a changing environment. Computational modelling revealed that participants leveraged relational knowledge to support inference, thus facilitating learning. Whole brain neuroimaging identified a uniquely robust representation of relational structure in the hippocampus. Neural networks trained on similar tasks demonstrated the emergence of relational structure representations, resembling those found in hippocampus. Lesioning network units sustaining such representations disrupted structure-based inference and predicted hippocampuss essential role. Transcranial ultrasound stimulation of human hippocampus, transiently modulating its activity without affecting overlying tissue, produced similar disruption effects, empirically confirming the causal necessity of hippocampal representations for structure-based inference in learning.

neuroscience↗

bioRxiv2025

Friend Request Accepted: Fundamental Features of Social Environments Determine Rate of Social Affiliation

Humans start new friendships and social connections throughout their lives and such relationships foster mental and physical well-being. While friendship initiation may depend on alignment of subtle and complex personal variables, here we investigated whether it also depends on basic features of social environments. This would be analogous to other fundamental behaviours like foraging which depend on basic features of the environment such as the density of opportunities and the likelihood of success. In a pre-registered online study (n=783), we found people were more likely to send friend requests as the density of friendship opportunities decreased and frequency of success increased. Further, we found task-related measures, like overall friend requests, were correlated with personality-related factors like social thriving and anhedonia. Next, in an ultra-high-field fMRI study (n=24), we found that both fundamental features of social environments - opportunity density and frequency of success - affected neural activity across a network of regions linked to foraging including dorsal raphe nucleus, substantia nigra, and anterior insula. Finally, in resting-state fMRI data (n=400), we showed that model predicted estimates of anhedonia were related to functional connectivity between components of the same network. Thus, humans consider the background statistics of an environment while making social decisions and these decisions are linked to activity in ancient subcortical circuits mediating the influence of environmental statistics on other aspects of behaviour. Moreover, individual differences in how environmental features influence social behaviour are associated with variation in personality and psychiatric traits, offering new insights into inter-individual variability in social functioning.

neuroscience↗