Biology subjects

Buccini, M.

Publications and source records attributed to Buccini, M..

3 recordsLinked to original sources

bioRxiv2025

Real-time Bayesian optimization of deep brain stimulation for personalized cognitive control enhancement

BackgroundIdentifying effective deep brain stimulation (DBS) parameters for psychiatric disorders has historically been a time-consuming and error prone process due to a lack of an objective and rapid readout of target circuit engagement. Cognitive control may have use as a biomarker of treatment efficacy but it has yet to be shown that DBS parameters can be reliably optimized to produce cognitive control improvements in individual subjects. ObjectiveWe sought to leverage a rat model of DBS-driven cognitive control improvements to determine whether state of the art optimization algorithms could consistently identify effective stimulation amplitudes to enhance cognition. MethodsWe delivered periods of active and inactive DBS-like stimulation at variable parameters while rats performed a Set-Shifting task that we previously showed to be stimulation-sensitive. We tested both predefined settings of interest and settings that were personalized to individual animals using Bayesian Optimization. Measurements of task performance including reaction time and accuracy were compared between acute, optimized, and traditional settings to evaluate effects on cognitive control. ResultsAcute stimulation reduced reaction times without hindering accuracy (N=15), replicating the effects previously observed with chronic stimulation. In a second cohort (N=6), optimization of stimulation amplitude successfully reduced reaction times in all animals with comparable effect size to historically best settings. ConclusionThese findings confirm that optimization techniques can be effective for improving symptomatically-relevant cognitive markers supporting the feasibility of personalized, quantitatively-informed approaches to neuromodulation and target engagement for psychiatric and/or cognitive disorders. HighlightsProving target engagement is a substantial challenge across brain stimulation modalities, and objective, rapid behavioral read-outs may be a solution to that challenge. Reaction times in cognitive control tasks are an example of a behavioral measure that changes rapidly in response to changes in stimulation parameters, and that also may predict clinical outcomes. Individually optimal stimulation amplitudes for reducing reaction time by stimulating corticofugal fibers passing through the striatum can be determined using Bayesian Optimization. Individually optimized settings discovered in an acute preparation demonstrate consistent effects when applied chronically.

neuroscience↗

bioRxiv2023

Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis modulates the behavioral consequences of unpredictable threat

Fear responses to perceived danger are critical for survival, as they prompt the individual to respond to threats and avoid harm. However, excessive fear can impede normal biological processes and become harmful. This study investigates the neural mechanisms underlying two distinct forms of fear--phasic and sustained--in male and female mice, with a focus on the bed nucleus of the stria terminalis (BNST) and corticotropin-releasing factor (CRF) signaling. Phasic fear is characterized by immediate responses to clear threats, while sustained fear is driven by ambiguous or uncertain cues and persists longer. Using rodent models, we found that sustained fear, modeled by partial fear conditioning, induced greater arousal and BNST activity in males, especially during ambiguous threat cues. In contrast, females exhibited reduced BNST and BNSTCRF activity, highlighting significant sex differences in fear learning and expression. Additionally, CRF is crucial for appropriate fear response in females, as CRF knockdown led to increased fear responses, but had no effect in males. These sex-specific differences could help inform the development of targeted treatments for anxiety and trauma-related disorders, which disproportionately affect women.

neuroscience↗

bioRxiv2022

Chronic Alcohol Consumption Alters Home-Cage Behaviors and Responses to Ethologically Relevant Predator Tasks in Mice

Alcohol use disorders (AUD) are the most prevalent substance use disorders worldwide. Considering recent reports indicating an increase in alcohol use particularly in females, it is vital to understand how alcohol history impacts behavior. Animal model research on withdrawal-associated affective states tends to focus on males, forced alcohol paradigms, and a few traditional anxiety/stress tests. While this has been essential, heavy alcohol use triggers adverse withdrawal-related affective states that can influence how people respond to a large variety of life events and stressors. To this end, we show that behaviors in the home-cage, open field, looming disc, and robogator predator threat task, which vary in task demand and intensity, are altered in mice with a history of voluntary alcohol consumption. In alcohol-exposed males, behaviors in the home cage, a low anxiety baseline environment, suggest increased vigilance/exploration. However, in the open field and robogator task, which induce heightened arousal and task demands, a more hesitant/avoidant phenotype is seen. Female alcohol mice show no behavioral alterations in the home cage and open field test, however, in the looming disc task, which mimics an overhead advancing predator and forces a behavioral choice, we see greater escape responses compared to water controls, indicative of active stress coping behaviors. This suggests females may begin to show alcohol-induced alterations as task demands increase. To date, few drugs have advanced past clinical trials for the treatment of AUD, and those that have are predominately used in life-threatening situations only. No treatments exist for ameliorating negative withdrawal related states, which could aid in harm reduction related to heavy alcohol use. Understanding how withdrawal alters a variety of behavioral responses that are linked to stress coping can widen our understanding of alcohol abuse and lead us closer to better therapeutics to help individuals with AUD.

neuroscience↗