Electronic Theses and Dissertations


Anna E. Liley



Document Type


Degree Name

Doctor of Philosophy



Committee Chair

Nicholas Simon

Committee Member

Nicholas W Simon

Committee Member

Helen J Sable

Committee Member

James G Murphy

Committee Member

Judith A Cole


The ability to accumulate rewards while minimizing negative consequences is a valuable survival skill. Importantly, many psychiatric diseases such as substance use disorder (SUD; Bechara, 2005; Gowin et al., 2013), attention deficit hyperactivity (Magnus et al., 2021), anxiety (Hartley and Phelps, 2012), major depressive, bipolar, and schizophrenia disorders (Whitton et al., 2015) involve impaired decision-making that can lead to detrimental outcomes. One factor that causes maladaptive decision-making is insensitivity to negative consequences, especially those that occur later in time (Murphy et al., 2001; Bechara and Dolan, 2002; Field et al., 2019). These studies were among the first to investigate how the orbitofrontal cortex, a brain region implicated in cost/benefit decision-making (Floresco et al., 2008) and reward discounting (Zeeb et al., 2010), contributes to the discounting of delayed punishment. Information gathered from the current work provided the first evidence that inactivation of lateral orbitofrontal cortex (LOFC) reduced choice of delayed punishment compared to saline baselines, and LOFC inhibition occurred prior to different types of safe reward choices compared to immediate punishment. Preliminary optogenetics data also found that pre-choice inhibition reduced delayed punishment choice. In summation, LOFC drives the undervaluation of delayed punishment, and future therapeutic treatments aiming to improve discounting of delayed punishments during decision-making would benefit from selectively suppressing LOFC activity.


Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest


Embargoed until 11/3/2023