Biology subjects

Nguyen, Q. N.

Publications and source records attributed to Nguyen, Q. N..

3 recordsLinked to original sources

bioRxiv2023

Dissociable causal roles of dorsolateral prefrontal cortex and primary motor cortex as a function of motor skill expertise

Established models of motor skill learning posit that early stages of learning are dominated by an attentionally demanding, effortful mode of control supported by associative corticostriatal circuits involving the dorsolateral prefrontal cortex (DLPFC). As expertise develops, automatic and "effortless" performance coincides with a transition to a reliance on sensorimotor circuits that include primary motor cortex (M1). However, the dynamics of how control evolves during the transition from novice to expert are currently unclear. This lack of clarity is due, in part, to the fact that most motor learning studies comprise a limited number of training sessions and rely on correlative techniques such as neuroimaging. Here, we train human participants on a discrete motor sequencing task over the course of six weeks, followed by an assessment of the causal roles of DLPFC and M1 at varying levels of expertise. We use repetitive transcranial magnetic stimulation to transiently disrupt activity in these regions immediately prior to performance in separate sessions. Our results confirm the dissociable importance of DLPFC and M1 as expertise develops. DLPFC stimulation leads to larger behavioral deficits for novice skills than expert skills, while M1 stimulation leads to relatively larger deficits as expertise develops. However, our results also reveal that prefrontal disruption causes performance deficits at all levels of expertise. These findings challenge existing models and indicate an evolving rather than a strictly diminishing role for DLPFC throughout learning. Significance StatementMotor skills involve the sequential chaining of individual actions. For example, playing the piano involves learning to rapidly transition to from one finger press to another. Human neuroimaging studies have shown that primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) support novice motor sequencing skills, but activity in both regions declines over training. This has been interpreted as increased efficiency in M1 and yet a reduction in the involvement of DLPFC as expertise develops. We causally test this assumption by using non-invasive brain stimulation to transiently disrupt cortical activity following extended skill training. Although we confirm dissociable contributions of DLPFC and M1 as expertise develops, we show that both regions are necessary for performance regardless of skill level.

neuroscience↗

bioRxiv2020

A qualitative difference in decision-making of rats vs. humans explained by quantitative differences in behavioral variability

When observers make rapid, difficult perceptual decisions, their response time is highly variable from trial to trial. In a visual motion discrimination task, it has been reported that human accuracy declines with increasing response time, whereas rat accuracy increases with response time. This is of interest because different mathematical theories of decision-making differ in their predictions regarding the correlation of accuracy with response time. On the premise that perceptual decision-making mechanisms are likely to be conserved among mammals, we seek to unify the rodent and primate results in a common theoretical framework. We show that a bounded drift diffusion model (DDM) can explain both effects with variable parameters: trial-to-trial variability in the starting point of the diffusion process produces the pattern typically observed in rats, whereas variability in the drift rate produces the pattern typically observed in humans. We further show that the same effects can be produced by deterministic biases, even in the absence of parameter stochasticity or parameter change within a trial.

neuroscience↗

bioRxiv2017

Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys.

Vertical HIV-1 transmission via breastfeeding is the predominant contributor to pediatric infections that are ongoing in this era of highly effective antiretroviral therapy (ART). Remarkably, only ~10% of infants chronically exposed to the virus via breastfeeding from untreated HIV-infected mothers become infected, suggesting the presence of naturally protective factors in breast milk. HIV-specific maternal antibodies are obvious candidates as potential contributors to this protection. This study assessed the protective capacity of common HIV envelope-specific non-broadly neutralizing antibodies isolated from breast milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. Prior to oral SHIV challenge, infant RMs were i.v. infused with either a single weakly-neutralizing monoclonal antibody (mAb), a tri-mAb cocktail with neutralizing and ADCC functionalities, or an anti-influenza HA control mAb. Of these groups, the fewest tri-mAb-treated infants developed plasma viremia (2/6, 3/6, and 6/8 animals viremic in tri-mAb, single-mAb, and control mAb groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer transmitted/founder SHIV variants in plasma and decreased peripheral CD4+ T cell proviral loads at 8 week post-challenge compared to control mAb-treated infants. Abortive infection was observed as detectable CD4+ T cell provirus in non-viremic control mAb- and single-mAb-, but not tri-mAb-treated animals. Taken together, these results support the potential viability of maternal or infant vaccine strategies that elicit non-broadly neutralizing antibodies to prevent vertical transmission of HIV through breastfeeding.

immunology↗