Biology subjects

Zorowitz, S.

Publications and source records attributed to Zorowitz, S..

3 recordsLinked to original sources

bioRxiv2022

A neural substrate of sex-dependent modulation of motivation by value

While there is emerging evidence of sex differences in decision-making behavior, the neural substrates that underlie such differences remain largely unknown. Here, we demonstrate that in mice performing a value-based decision-making task, while choices are similar between the sexes, motivation to engage in the task is modulated by action value in females more strongly than in males. Inhibition of activity in anterior cingulate cortex (ACC) neurons that project to the dorsomedial striatum (DMS) disrupts this relationship between value and motivation preferentially in females, without affecting choice in either sex. In line with these effects, in females compared to males, ACC-DMS neurons have stronger representations of negative outcomes, and more neurons are active when the value of the chosen option is low. In contrast, the representation of each choice is similar between the sexes. Thus, we identify a neural substrate that contributes to sex-specific modulation of motivation by value.

neuroscience↗

bioRxiv2019

Bidirectional modulation of human emotional conflict resolution using intracranial stimulation

The ability to regulate emotions in the service of meeting ongoing goals and task demands is a key aspect of adaptive human behavior in our volatile social world. Consequently, difficulties in processing and responding to emotional stimuli underlie many psychiatric diseases ranging from depression to anxiety, the common thread being effects on behavior. Behavior, which is made up of shifting, difficult to measure hidden states such as attention and emotion reactivity, is a product of integrating external input and latent mental processes. Directly measuring, and differentiating, separable hidden cognitive, emotional, and attentional states contributing to emotion conflict resolution, however, is challenging, particularly when only using task-relevant behavioral measures such as reaction time. State-space representations are a powerful method for investigating hidden states underlying complex systems. Using state-space modeling of behavior, we identified relevant hidden cognitive states and predicted behavior in a standardized emotion regulation task. After identifying and validating models which best fit the behavior and narrowing our focus to one model, we used targeted intracranial stimulation of the emotion regulation-relevant neurocircuitry, including prefrontal structures and the amygdala, to causally modulate separable states. Finally, we focused on this one validated state-space model to perform real-time, bidirectional closed-loop adaptive stimulation in a subset of participants. These approaches enable an improved understanding of how to sample and understand emotional processing in a way which could be leveraged in neuromodulatory therapy for disorders of emotional regulation.

neuroscience↗

bioRxiv2019

Anxiety, avoidance, and sequential evaluation

Anxiety disorders are characterized by a range of aberrations in the processing of and response to threat, but there is little clarity what core pathogenesis might underlie these symptoms. Here we propose that a particular set of unrealistically pessimistic assumptions can distort an agents behavior and underlie a host of seemingly disparate anxiety symptoms. We formalize this hypothesis in a decision theoretic analysis of maladaptive avoidance and a reinforcement learning model, which shows how a localized bias in beliefs can formally explain a range of phenomena related to anxiety. The core observation, implicit in standard decision theoretic accounts of sequential evaluation, is that the potential for avoidance should be protective: if danger can be avoided later, it poses less threat now. We show how a violation of this assumption -- via a pessimistic, false belief that later avoidance will be unsuccessful -- leads to a characteristic, excessive propagation of fear and avoidance to situations far antecedent of threat. This single deviation can explain a range of features of anxious behavior, including exaggerated threat appraisals, fear generalization, and persistent avoidance. Simulations of the model reproduce laboratory demonstrations of abnormal decision making in anxiety, including in situations of approach-avoid conflict and planning to avoid losses. The model also ties together a number of other seemingly disjoint phenomena in anxious disorders. For instance, learning under the pessimistic bias captures a hypothesis about the role of anxiety in the later development of depression. The bias itself offers a new formalization of classic insights from the psychiatric literature about the central role of maladaptive beliefs about control and self-efficacy in anxiety. This perspective also extends previous computational accounts of beliefs about control in mood disorders, which neglected the sequential aspects of choice.

neuroscience↗