The Ghahreman Khodadad Center for the Study of Excessive Pathological Selfishness

Cutting-Edge Research

At the Khodadad Center, we are at the forefront of research into the neurological mechanisms of excessive pathological selfishness. Leveraging state-of-the-art brain imaging technologies and the School of Medicine’s extensive expertise in developing animal models, we seek to understand the biological drivers of EPS. Researchers at the center are tackling the challenge of identifying the core neural circuits that underlie pathological selfishness and the mechanisms that propel it, which has the potential not only to advance our understanding of human behavior but also to improve mental health and prevent harm.

Elizabeth Byrnes, Professor of Comparative Pathobiology
Project: Opioid use disorder, maternal care, and the development of social behaviors

Clinical findings implicate parental neglect as a critical factor in the etiology of personality disorders, including narcissistic personality disorder. Maternal substance use is a significant risk factor for neglect. Moreover, recent findings suggest women who maintain their recovery from opioid use disorder with medication-assisted treatment (i.e. methadone or buprenorphine), still demonstrate blunted maternal sensitivity, suggesting continued risk even in women who do not relapse. As we are currently in the midst of an opioid epidemic, with rates of neonatal abstinence rising over 500% in the last decade, rates of childhood neglect leading to intergenerational transmission of personality disorders, including those that feature excessive pathological selfishness (EPS), are likely to increase. We have a well-established model of prenatal opioid use disorder and a history of studying the intergenerational effects of opioids. The goal of the current set of studies would be to expand our efforts to identify changes in the maternal brain network induced by opioid use and correlate those effects with the adult prosocial and/or antisocial behaviors in offspring reared by opioid dependent mothers. These studies would provide preliminary data to advance mechanistic studies aimed at mitigating the effects of prenatal opioid use on maternal behavior in an effort to prevent the development of antisocial behaviors, including EPS, in the next generation.

Martina Chiacchiaretta, Postdoctoral Scholar in the Department of Neuroscience
Project: Exploring the Influence of Sleep/Wake Cycle on Social Decision-Making

In the United States alone, more than 7 million individuals experience sleep disturbances, contributing to what can be described as a "sleep epidemic." Understanding the impact of sleep disorders on our social behavior is of utmost importance. Recent research has demonstrated that sleep deprivation in humans leads to an increase in selfishness and a decrease in the inclination to help others. Furthermore, sleep disruption has been associated with social isolation and withdrawal. However, the underlying mechanisms responsible for these behaviors remain unclear. This study aims to investigate the potential involvement of orexinergic neurons located in the lateral hypothalamus (LH), a brain region known for its crucial role in regulating the sleep-wake cycle, in the decision-making process related to pro-social and selfish choices. We will explore whether dysregulation of orexinergic activity contributes to excessive pathological selfishness. This investigation holds particular significance due to the observed alterations in orexinergic activity and degeneration of these neurons in conditions such as Narcolepsy, Alzheimer's disease, mental disorders, and aging, where individuals suffer from sleep disturbances and behavioral dysfunctions.

Chris Dulla, Interim Chair and Professor of Neuroscience 
Project: Can traumatic brain injury reveal brain circuits of Excessive Pathological Selfishness?

Selfishness is a part of human behavior, critical to survival. Excessive pathological selfishness, however, drives greed, violence, and the worst aspects of human nature. We know very little about the circuits that drive selfishness, or the inverse, empathy. Interestingly, traumatic brain injury (TBI) causes behavioral changes consistent with EPS. Selfish behaviors, impulsivity, and “pseudo-psychopathic’ behavior all occur following TBI. We believe that studying the injured brain may reveal novel circuit-level changes that contribute to EPS. The anterior cingulate cortex (ACC) is a brain region associated with perceiving the emotional state of others, is activated when observing pain in others, and is involved in social cues signaling empathy. It is unknown if there is a direct link between injury-induced ACC dysfunction and EPS. We propose to use a rodent model of TBI, controlled cortical impact (CCI), to probe the relationship between ACC dysfunction and observational fear learning, a proxy for pathological selfishness. We hypothesize that TBI decreases ACC connectivity and disrupts coordinated activity between ACC and other cortical regions, contributing to pathological selfish behavior. We will utilize in vivo mesoscale GCaMP6 calcium imaging of the cortex, behavioral analysis of empathy, and viral tracing of ACC circuit connectivity to test our hypothesis.

Jamie Maguire, Kenneth and JoAnn G Wellner Professor of Neuroscience

The study of excessive pathological selfishness (EPS) requires a paradigm to experimentally measure selfishness. The Maguire Lab has designed and implemented an observational fear model to measure empathy in mice. Mice are housed in a chamber adjacent to a conspecific which is subjected to a series of foot shocks. The observer can see, hear, and smell the neighboring mouse being subjected to the foot shocks. Although never being subjected to the direct threat, the observer mice display a behavioral fear response, a demonstration of empathy. Using this model, we are able to stratify low and high empathy animals to investigate the mechanisms contributing to empathy. We have explored the neural circuits activated in high vs. low empathy mice to understand the neurocircuitry of empathy in mice. Further, we have demonstrated that both the direct and observed threat decreases endogenous neurosteroid synthesis. Pharmacological or genetic inhibition of endogenous neurosteroid synthesis is sufficient to increase the behavioral fear response in observers; whereas, treating mice with an exogenous neurosteroid is sufficient to reduce the behavioral expression of fear in the observational fear paradigm. These studies are beginning to unravel the mechanisms mediating empathy in mice with the goal of gaining an understanding of the mechanisms contributing to EPS.

Grant Weiss, Behavior Core Manager 
Project: Determining a Novel Set of Behaviors to Assess Excessive Pathological Selfishness

The balance of one’s selfishness and altruism are crucial for survival. Many animal models attempt to study Excessive Pathological Selfishness (EPS) by inducing pathology states, but here we aim to look instead for individual differences in natural selfish behaviors in the commonly used C57/Bl6 mouse strain. By using an automated, non-biased motion sequencing software, called MoSeq, to determine previously unnoticed behavioral motifs, we can build a set of behaviors that can then be used to assess the selfishness of a mouse. Using a previously described paradigm of observational fear as a measure of empathy, mice are separated into low and high empathy groups to compare their behaviors. The MoSeq pipeline identifies behavior segments with sub-second duration, or “behavioral syllables”, which produces a richer, larger pool of data from which to extract the most robust behaviors. Furthermore, behaviors related to EPS can also be found by treating mice with the reported pro-social compounds: oxytocin, and vasopressin. By comparing the behavioral differences in pro-social mice with differences across individuals in the observational fear paradigm, we can build a reliable set of selfish behavioral syllables in mice. Because these behaviors are not reliant on fear or motivation, it is possible that they could be used to predict the empathy of an individual based on their natural behavior. Importantly, this set of selfish behaviors could then be used by future researchers to determine the neural, genetic, and/or developmental differences that underlie EPS.

Ghahreman Khodadad is a retired neurosurgeon and professor emeritus at the University of Cincinnati, where he was a member of the faculty of the Department of Neurosurgery. After earning his medical degree from Tehran School of Medicine in Iran, he worked at the University of Pennsylvania School of Medicine before joining the University of Cincinnati, where he spent most of his career. The study of Excessive Pathological Selfishness has been a life-long passion for Khodadad. He believes many of the conflicts in the world are founded in greed.