Biology subjects

Hakimi, S.

Publications and source records attributed to Hakimi, S..

3 recordsLinked to original sources

bioRxiv2023

Coupling of renal sodium and calcium transport: A modeling analysis

Calcium (Ca2+) transport along the nephron occurs via specific transcellular and paracellular pathways, and is coupled to the transport of other electrolytes. Notably sodium (Na+) transport establishes an electrochemical gradient to drive Ca2+ reabsorption. Hence, alterations in renal Na+ handling, under pathophysiological conditions or pharmacological manipulations, can have major effects on Ca2+ transport. An important class of pharmacological agent is diuretics, which are commonly prescribed for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate Na+ transport, but also indirectly affect renal Ca2+ handling. To better understand the underlying mechanisms, we have developed a computational model of electrolyte transport along the superficial nephron in the kidney of a male and female rat. Sex differences in renal Ca2+ handling are represented. Model simulations predict in the female rat nephron lower Ca2+ reabsorption in the proximal tubule and thick ascending limb, but higher reabsorption in the late distal convoluted tubule and connecting tubule, compared to the male nephron. The male rat kidney model yields a higher urinary calcium excretion than female, consistent with animal experiments. Additionally, we conducted simulations of inhibition of channels and transporters that play a major role in Na+ and Ca2+ transport. Model results indicate that along the proximal tubule and ascending thick ascending limb, Ca2+ and Na+ transport occurs in parallel, but those processes are dissociated in the distal convoluted tubule. Simulations also reveal sex-specific responses to different pharmacological manipulations.

physiology↗

bioRxiv2022

Between heuristics and optimality: Flexible integration of cost and evidence during information sampling

Effective decision making in an uncertain world requires balancing the benefits of acquiring relevant information with the costs of delaying choice. Optimal strategies for information sampling can be accurate but computationally expensive, whereas heuristic strategies are often computationally simple but rigid. To characterize the computations that underlie information sampling, we examined choice processes in human participants who sampled sequences of images (e.g. indoor and outdoor scenes) and attempted to infer the majority category (e.g. indoor or outdoor) under two reward conditions. We examined how behavior maps onto potential information sampling strategies. We found that choices were best described by a flexible function that lay between optimality and heuristics; integrating the magnitude of evidence favoring each category and the number of samples collected thus far. Integration of these criteria resulted in a trade-off between evidence and samples collected, in which the strength of evidence needed to stop sampling decreased linearly as the number of samples accumulated over the course of a trial. This non-optimal trade-off best accounted for choice behavior even under high reward contexts. Our results demonstrate that unlike the optimal strategy, humans are performing simple accumulations instead of computing expected values, and that unlike a simple heuristic strategy, humans are dynamically integrating multiple sources of information in lieu of using only one source. This evidence-by-costs tradeoff illustrates a computationally efficient strategy that balances competing motivations for accuracy and cost minimization.

animal behavior and cognition↗

bioRxiv2020

Distinct brain mechanisms linked to evidence accumulation and crime-type bias in juror decisions

Efforts to explain complex human decisions have focused on competing theories emphasizing utility and narrative mechanisms. These are difficult to distinguish using behavior alone. Both narrative and utility theories have been proposed to explain juror decisions, which are among the most consequential complex decisions made in a modern society. Here, we asked jury-eligible male and female subjects to rate the strength of a series of criminal cases while recording the resulting patterns of brain activation. We compared patterns of brain activation associated with evidence accumulation to patterns of brain activation derived from a large neuroimaging database to look for signatures of the cognitive processes associated with different models of juror decision making. Evidence accumulation correlated with multiple narrative processes, including reading and recall. Of the cognitive processes traditionally viewed as components of utility, activation patterns associated with uncertainty, but not value, were more active with stronger evidence. Independent of utility and narrative, activations linked to reasoning and relational logic also correlated with increasing evidence. Hierarchical modeling of cognitive processes associated with evidence accumulation supported a more prominent role for narrative in weighing evidence in complex decisions. However, utility processes were also associated with evidence accumulation. These complementary findings support an emerging view that integrates utility and narrative processes in complex decisions. Significance StatementThe last decade has seen a sharply increased interest in narrative as a central cognitive process in human decision making and as an important factor in the evolution of human societies. However, the roles of narrative versus utility models of decision making remain hotly debated. While available models frequently produce similar behavioral predictions, they rely on different cognitive processes and so their roles can be separated using the right neural tests. Here, we use brain imaging during mock juror decisions to show that cognitive processes associated with narrative, and to a lesser extent utility, were engaged while subjects evaluated evidence. These results are consistent with interactions between narrative and utility processes during complex decision making.

neuroscience↗