bioRxiv Science⌕ Search

Biology subjects

Bader, F.

Publications and source records attributed to Bader, F..

6 recordsLinked to original sources
bioRxiv2025

Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects

BackgroundOxytocin (OT) is a key neuromodulator of social behavior in mammals, and accumulating evidence supports the existence of a critical period for OT action during infancy. However, other developmental windows remain poorly explored, and it remains unclear whether OT exert distinct functions depending on the timing of its activity. In this study, we aimed to determine whether specific developmental stages exist during which OT-expressing neurons play a decisive role with long-term consequences. MethodsWe used a chemogenetic approach to transiently inhibit OT-expressing neurons during three postnatal developmental periods: infancy, the juvenile period, and young adulthood in male and female mice. Behavioral and metabolic outcomes were then assessed longitudinally. We also examined the effects of inhibiting OT neurons during late fetal stages and at birth. ResultsSocial memory was consistently impaired in males, regardless of the timing of neuronal inactivation. The most pronounced behavioral effects were observed following inhibition during infancy in both sexes. Metabolically, adult males from all cohorts exhibited increased body weight, whereas increased fat mass and adipocyte size hypertrophy were specifically observed following inhibition during the juvenile period. Notably, inhibition of OT-expressing neurons around the time of birth resulted in delayed parturition and altered neonatal feeding behavior. LimitationsOT-expressing neurons release multiple signaling molecules. However, converging evidence suggests that the observed phenotypes are primarily attributable to OT deficiency. Although this study demonstrates long-term behavioral and metabolic consequences of transient OT neuron inhibition, further experiments are required to elucidate underlying mechanisms and identify additional effects. ConclusionsTransient inhibition of OT-expressing neurons during distinct postnatal developmental periods leads to long-lasting effects on social behavior and metabolism, with outcomes depending on both the timing of inhibition and sex. Furthermore, our findings reveal an unexpected role for fetal/neonatal OT neurons in regulating the timing of birth and early feeding behavior.

neuroscience↗
bioRxiv2025

The NIH BRAIN Initiative's Experiment in Team Research

Withdrawal StatementThe authors have withdrawn this manuscript because this manuscript has been merged with another preprint (BIORXIV/2025/635684). Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The merged preprint can be found at doi:10.1101/2025.01.30.635684

neuroscience↗
bioRxiv2023

Neuroimaging Signatures of Metacognitive Improvement in Sensorimotor Timing

Error monitoring is an essential human ability underlying learning and metacognition. In the time domain, humans possess a remarkable ability to learn and adapt to temporal intervals, yet the neural mechanisms underlying this are not well understood. Recently, we demonstrated that humans exhibit improvements in sensorimotor time estimates when given the chance to incorporate feedback from a previous trial (Bader and Wiener 2021), suggesting that humans are metacognitively aware of their own timing errors. To test the neural basis of this metacognitive ability, human participants of both sexes underwent fMRI while they performed a visual temporal reproduction task with randomized suprasecond intervals (1-6s). Crucially, each trial was repeated following feedback, allowing a "re-do" to learn from the successes or errors in the initial trial. Behaviorally, we replicated our previous finding that subjects improve their performance on re-do trials despite the feedback being temporally uninformative (i.e. early or late). For neuroimaging, we observed a dissociation between estimating and reproducing time intervals, with the former more likely to engage regions associated with the default mode network (DMN), including the superior frontal gyri, precuneus, and posterior cingulate, whereas the latter activated regions associated traditionally with the "Timing Network" (TN), including the supplementary motor area (SMA), precentral gyrus, and right supramarginal gyrus. Notably, greater DMN involvement was observed in Re-do trials. Further, the extent of the DMN was greater on re-do trials, whereas for the TN it was more constrained. Finally, Task-based connectivity between these networks demonstrated higher inter-network correlation on initial trials, but primarily when estimating trials, whereas on re-do trials communication was higher during reproduction. Overall, these results suggest the DMN and TN work in concert to mediate subjective awareness of ones sense of time for the purpose of improving timing performance. Significance StatementA finely tuned sense of time perception is imperative for everyday motor actions (e.g., hitting a baseball). Timing self-regulation requires correct assessment and updating duration estimates if necessary. Using a modified version of a classical task of time measurement, we explored the neural regions involved in error detection, time awareness, and learning to time. Reinforcing the role of the SMA in measuring temporal information and providing evidence of co-activation with the DMN, this study demonstrates that the brain overlays sensorimotor timing with a metacognitive awareness of its passage.

neuroscience↗
bioRxiv2022

Anchors for Time, Distance, and Magnitude in Virtual Movements

In order to navigate through the environment, humans must be able to measure both the distance traveled in space, and the interval covered in time. Yet, how these two dimensions are computed and interact across neural systems remains unknown. One possibility is that subjects measure how far and how long they have traveled relative to a known reference point, or anchor. To measure this, we had human participants (n=24) perform a distance estimation task in a virtual environment in which they were cued to attend to either the spatial or temporal interval traveled, while responses were measured with multiband fMRI. We observed that both dimensions evoked similar frontoparietal networks, yet with a striking rostrocaudal dissociation between temporal and spatial estimation. Multivariate classifiers trained on each dimension were further able to predict the temporal or spatial interval traveled, with centers of activation within the supplementary motor area (SMA) and retrosplenial cortex (RSC) for time and space, respectively. Further, a cross-classification approach revealed the right supramarginal gyrus (SMG) and occipital place area (OPA) as regions capable of decoding the general magnitude of the traveled distance. Altogether, our findings suggest the brain uses separate systems for tracking spatial and temporal distances, which are combined together along with amodal estimates.

neuroscience↗
bioRxiv2020

Modulation of Individual Alpha Frequency with tACS shifts Time Perception

Previous studies have linked brain oscillation and timing, with evidence suggesting that alpha oscillations (10Hz) may serve as a "sample rate" for the visual system. However, direct manipulation of alpha oscillations and time perception has not yet been demonstrated. Eighteen subjects performed a time generalization task with visual stimuli. Participants first learned the standard intervals (600 ms) and then were required to judge the new temporal intervals if they were equal or different compared to the standard. Additionally, we had previously recorded resting-state EEG from each subject and calculated their Individual Alpha Frequency (IAF), estimated as the peak frequency from the mean spectrum over posterior electrodes between 8 and 13 Hz. After learning the standard interval, participants performed the time generalization task while receiving occipital transcranial Alternating Current Stimulation (tACS). Crucially, for each subject, tACS was administered at their IAF or at off-peak alpha frequencies (IAF{+/-}2 Hz). Results demonstrated a linear shift in the psychometric function indicating a modification of perceived duration, such that progressively "faster" alpha stimulation led to longer perceived intervals. These results provide the first evidence that direct manipulations of alpha oscillations can shift perceived time in a manner consistent with a clock speed effect.

neuroscience↗