Biology subjects

Froelich, S.

Publications and source records attributed to Froelich, S..

3 recordsLinked to original sources

bioRxiv2024

Context-Dependent Interaction Between Goal-Directed and Habitual Control Under Time Pressure

Habits are an important aspect of human behaviour. Habits are reflexive, inflexible, and fast, in contrast to goal-directed behaviour which is reflective, flexible, and slow. Current theories assume that habits and goal-directed actions are controlled by two separate but interacting systems. However, it is not clear how these two systems interact when actions must be made under time pressure. Here we use a task which induces habitual behaviour in the form of action sequences, while concurrently requiring participants to perform goal-directed actions that are either congruent or incongruent with the habit. This task thus allows for concurrent measurement of both goal-directed and habitual behaviour, thereby permitting a nuanced analysis of the interaction between these two control modes. Using computational modelling, we find that models where the influence of the habit depends on the number of repetitions, explain participant behaviour better than models that assume the habit to be constant. We further show that roughly half of the participants modulate their use of the habit depending on the context, i.e. they selectively inhibit the habits influence when it is incongruent to their explicit goals, but not when both are congruent and the influence of the habit is adaptive. Additional drift-diffusion modelling of choice and reaction time data shows that proactive control is mobilized in the congruent task context whereas reactive control is mobilized in the incongruent task context. The present study thus indicates that habitual control is context-dependent and can be adaptively deployed via proactive and reactive control, rather than being a fixed or isolated mechanism.

neuroscience↗

bioRxiv2022

Interaction of automatic motor and goal-directed behavior under time pressure

Human behaviour consists in large parts of action sequences that are often repeated in mostly the same way. Through extensive repetition, sequential responses become automatic or habitual, but our environment often confronts us with events to which we have to react flexibly and in a goal-directed manner. To assess how implicitly learned action sequences interfere with goal-directed control, we developed a novel behavioural paradigm in which we combined action sequence learning through repetition with a goal-directed task component. So-called dual-target trials require the goal-directed selection of the response with the highest reward-probability in a fast succession of trials with short response deadlines. Importantly, the response primed by the learned action sequence is sometimes different from that required by the goal-directed task. As expected, we found that participants learned the action sequence through repetition, as evidenced by reduced reaction times and error rates, while still acting in a goal-directed manner in dual target trials. Specifically, we found that the learned action sequence biased choices in the goal-directed task towards the sequential response, and this effect was more pronounced the better individuals had learned the sequence. Our novel task may help shed light on the acquisition of automatic behavioural patterns and habits through extensive repetition, allows to assess positive features of habitual behaviour (e.g. increased response speed and reduced error rates), and importantly also the interaction of habitual and goal-directed behaviours under time pressure.

animal behavior and cognition↗

bioRxiv2020

Identifying therapeutic drug targets for rare and common forms of short stature

While GWAS of common diseases has delivered thousands of novel genetic findings, prioritizing genes for translation to therapeutics has been challenging. Here, we propose an approach to resolve that issue by identifying genes that have both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). Bidirectionality is a desirable feature of the best targets because it implies both a causal role on the phenotype in one direction and that modulating the target activity might be safe and therapeutically beneficial in the other. We used height, a highly heritable trait and a model of complex diseases, to test our approach. Using 34,231 individuals with exome sequence data and height, we identified five genes (IGF1R, NPPC, NPR2, FGFR3, and SHOX) with evidence for bidirectional effects on stature. Rare protein-altering variants significantly increased risk for idiopathic short stature (ISS) (OR=2.75, p= 3.99x10-8). These genes are key members of the only two pathways successfully targeted for short stature: Growth Hormone/Insulin-like growth factor 1 axis and C-type Natriuretic peptide (CNP) for Achondroplasia, a monogenic form of dwarfism. We assayed a subset of NPR2 mutations and identified those with elevated (GoF) and diminished (LoF) activity and found that a polygenic score for height modulates the penetrance of pathogenic variants. We also demonstrated that adding exogenous CNP (encoded by NPPC) rescues the NPR2 haploinsufficiency molecular phenotype in a CRISPR-engineered cell line, thus validating its potential therapeutic treatment for inherited forms of short stature. Finally, we found that these BEST targets increase the probability of success in clinical trials above and beyond targets with other genetic evidence. Our results show the value of looking for bidirectional effects to identify and validate drug targets.

genetics↗