Social and economic decision-making in Urbach-Wiethe Disease

Background: Rodent and primate research have identified the basolateral amygdala as indispensable for social decision-making. This finding has not yet been translated to humans, and has even been partially contradicted by previous findings in patients with amygdala lesions that show generous economic investments in strangers. This thesis therefore aimed to determine whether selective basolateral amygdala damage in humans, caused by Urbach-Wiethe Disease, impairs instrumental non-social economic decision-making. Methods: Using an adapted reinforcement-learning task, the performance of basolateral amygdala damaged individuals (n=6) was compared with that of healthy controls (n=20) on social and economic decision-making during a probabilistic reinforcement task. The task required participants to make decisions for themselves and others based on learned probability of monetary reward or loss. A random effects Generalised Least Squares regression was conducted using Stata 15.1. to assess discrimination between Gain and Loss domains. A social-decision making task was also administered. Results: When making choices for themselves, Urbach-Wiethe Disease participants showed no difference in correct choices made between Gain and Loss domains. The Urbach-Wiethe disease participant's lack of discrimination between gains and losses for themselves was significantly different (p< 0.01) from that of controls, who made significantly more correct choices for themselves in the gain domain compared to the Loss domain. Social decision-making performance did not, however, differ significantly between Urbach-Wiethe Disease participants and controls. Conclusions: These findings regarding non-social decision-making support the important role of the basolateral amygdala as a salience detector, with lesions to this region resulting in reduced bias to the valence of potential economic outcomes, regardless of whether these pertain to costs or benefits. These findings are also consistent with prior work indicating that lesions to the basolateral amygdala can possibly produce loss-aversion due to a hypervigilance for fear and the lack of inhibition of the centromedial amygdala by the basolateral amygdala

The Human Basolateral Amygdala Is Indispensable for Social Experiential Learning

Trust and betrayal are central to our social world, and adaptive responses to generous and selfish behavior are crucial to our economic and social well-being [1]. We learn about others’ trustworthiness through trial and error during repeated interactions [2]. By reinforcing and suppressing behavior during positive and negative interactions with conspecifics, rodent research has established a crucial role for the basolateral amygdala (BLA) in social experiential learning [3, 4]. The human BLA has undergone a reorganization with massive expansion relative to other amygdala nuclei [5], and there is no translational research on its role in experiential learning. The human amygdala is traditionally researched as a single structure [6], neglecting the sub-nuclei's structural und functional differences [7], which might explain inconsistent findings in research on social interactions [8, 9]. Here, we study whether the human BLA is necessary for social and non-social experiential learning by testing a group of five humans with selective bilateral damage to the BLA. We compared their learning behavior in a repeated trust game, and a non-social control task, to healthy, matched controls. Crucially, BLA-damaged subjects, unlike control subjects, completely failed to adapt their investments when interacting with a trustworthy and an untrustworthy partner. In the non-social task, BLA-damaged subjects learned from positive outcomes but differed from the controls by not learning from negative outcomes. Our data extend findings in rodent research by showing that the human BLA is essential for social experiential learning and provide confirmatory evidence of divergent mechanisms for differentially valenced outcomes in non-social learning

The Human Basolateral Amygdala Is Indispensable for Social Experiential Learning

Trust and betrayal are central to our social world, and adaptive responses to generous and selfish behavior are crucial to our economic and social well-being [1]. We learn about others’ trustworthiness through trial and error during repeated interactions [2]. By reinforcing and suppressing behavior during positive and negative interactions with conspecifics, rodent research has established a crucial role for the basolateral amygdala (BLA) in social experiential learning [3, 4]. The human BLA has undergone a reorganization with massive expansion relative to other amygdala nuclei [5], and there is no translational research on its role in experiential learning. The human amygdala is traditionally researched as a single structure [6], neglecting the sub-nuclei's structural und functional differences [7], which might explain inconsistent findings in research on social interactions [8, 9]. Here, we study whether the human BLA is necessary for social and non-social experiential learning by testing a group of five humans with selective bilateral damage to the BLA. We compared their learning behavior in a repeated trust game, and a non-social control task, to healthy, matched controls. Crucially, BLA-damaged subjects, unlike control subjects, completely failed to adapt their investments when interacting with a trustworthy and an untrustworthy partner. In the non-social task, BLA-damaged subjects learned from positive outcomes but differed from the controls by not learning from negative outcomes. Our data extend findings in rodent research by showing that the human BLA is essential for social experiential learning and provide confirmatory evidence of divergent mechanisms for differentially valenced outcomes in non-social learning