Extinction circuits for fear and addiction overlap in prefrontal cortex

Extinction is a form of inhibitory learning that suppresses a previously conditioned response. Both fear and drug seeking are conditioned responses that can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders and addiction, respectively. Recent evidence indicates that the medial prefrontal cortex (mPFC) is critical for the extinction of both fear and drug-seeking behaviors. Moreover, a dorsal-ventral distinction is apparent within the mPFC, such that the prelimbic (PL-mPFC) cortex drives the expression of fear and drug seeking, whereas the infralimbic (IL-mPFC) cortex suppresses these behaviors after extinction. For conditioned fear, the dorsal-ventral dichotomy is accomplished via divergent projections to different subregions of the amygdala, whereas for drug seeking, it is accomplished via divergent projections to the subregions of the nucleus accumbens. Given that the mPFC represents a common node in the extinction circuit for these behaviors, treatments that target this region may help alleviate symptoms of both anxiety and addictive disorders by enhancing extinction memory.Emotional memories, both in the aversive and appetitive domains, are important for guiding behavior. Regulating the expression of these memories is critical for mental health. Extinction of classical conditioning is one form of emotion regulation that is easily modeled in animals. In the aversive domain, a conditioned stimulus (CS) is typically paired with a shock, while in the appetitive domain, a CS is paired with the availability of food or drug reward. Repeated presentation of the CS in the absence of the reinforcer leads to extinction of conditioned fear or drug-seeking behaviors. In recent years, there have been great advances in our understanding of the neural circuitry responsible for this form of inhibitory learning (for reviews, see Cammarota et al. 2005; Maren 2005; Myers and Davis 2007; Quirk and Mueller 2008). The prefrontal cortex has been strongly implicated in fear expression (Powell et al. 2001; Vidal-Gonzalez et al. 2006; Corcoran and Quirk 2007) and fear extinction (Herry and Garcia 2002; Milad and Quirk 2002; Gonzalez-Lima and Bruchey 2004; Hugues et al. 2004; Burgos-Robles et al. 2007; Hikind and Maroun 2008; Lin et al. 2008; Mueller et al. 2008; Sotres-Bayon et al. 2008), and more recently, in expression of drug seeking after extinction (Peters et al. 2008a,b). These findings are consistent with a well-documented role of the prefrontal cortex in executive function and emotional regulation (Miller 2000; Fuster 2002; Quirk and Beer 2006; Sotres-Bayon et al. 2006).In this review, we propose that the medial prefrontal cortex (mPFC) regulates the expression of both fear and drug memories after extinction, through divergent projections to the amygdala and nucleus accumbens, respectively. Extinction failure in the aversive domain can lead to anxiety disorders (Delgado et al. 2006; Milad et al. 2006), while extinction failure in the appetitive domain can lead to relapse in addicted subjects (Kalivas et al. 2005; Garavan and Hester 2007). A common neural circuit for extinction of fear and drug memories would suggest shared mechanisms and treatment strategies across both domains.     

Expansion of Genetic Services Utilizing a General Genetic Counseling Clinic

We established a general genetic counseling clinic (GCC) to help reduce long wait times for new patient appointments and to enhance services for a subset of patients. Genetic counselors, who are licensed in Tennessee, were the primary providers and MD geneticists served as medical advisors. This article describes the clinic referral sources, reasons for referral and patient dispositions following their GCC visit(s). We obtained patients by triaging referrals made to our medical genetics division. Over 24 months, our GCC provided timely visits for 321 patients, allowing the MD geneticists to focus on patients needing a clinical exam and/or complex medical management. Following their GCC visit(s), over 80 % of patients did not need additional appointments with an MD geneticist. The GCC allowed the genetic counselor to spend more time with patients than is possible in our traditional medical genetics clinic. Patient satisfaction surveys (n?=?30) were very positive overall concerning the care provided. Added benefits for the genetic counselors were increased professional responsibility, autonomy and visibility as health care providers. We conclude that genetic counselors are accepted as health care providers by patients and referring providers for a subset of clinical genetics cases. A GCC can expand genetic services, complement more traditional genetic clinic models and utilize the strengths of the genetic counselor health care provider.     

Personality Assessment in Today's Health Care Environment: Therapeutic Alliance and Patient Satisfaction

This autobiography traces my professional and, to a lesser extent, personal life through my career as a forensic and correctional psychologist. As an only child living in the country and later attending boarding schools from the fifth grade through high school, I learned to be self-reliant and independent. These traits led me to join an archaeological expedition to Oaxaca when I was 18, which fostered my interest in anthropology and then psychology at Amherst. I survived the clinical training program at the University of California at Berkeley and while still in graduate school obtained a staff position at the Alameda County Probation Department Guidance Clinic where I began my interrelated research paths on clinical assessment and the dynamics of aggression, paths I continued as an assistant professor at the University of Texas (1964–1967) and as an associate to full professor at the Florida State University (1967–2003). My major research contributions have been the (a) delineation of the overcontrolled and undercontrolled assaultive syndromes; (b) development of the MMPI–2 (Butcher, Dahlstrom, Graham, Tellegen, &; Kaemmer, 1989 Butcher, J. N., Dahlstrom, W. G., Graham, J. R., Tellegen, A. and Kaemmer, B. 1989. MMPI-2: Minnesota Multiphasic Personality Inventory–2: Manual for administration and scoring, Minneapolis: University of Minnesota Press.  [Google Scholar]) Overcontrolled Hostility (O–H) Scale; (c) formulation of the “Algebra of Aggression,” a theoretical framework for evaluating and understanding aggressive behavior; (d) exploration of how gender roles interact with dominance in leadership assumption; (e) empirical demonstration of the adverse effects of population density on adjustment in correctional institutions; and (f) development and validation of a classification system for adult criminal offenders based on the MMPI–2.     

Recalling safety: cooperative functions of the ventromedial prefrontal cortex and the hippocampus in extinction

Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.     

Affective forecasting and the Big Five

Recent studies on affective forecasting clarify that the emotional reactions people anticipate often differ markedly from those they actually experience in response to affective stimuli and events. However, core personality differences in affective forecasting have received limited attention, despite their potential relevance to choice behavior. In the present study, 226 college undergraduates rated their anticipated and experienced reactions to the emotionally-evocative event of Valentine's Day and completed a measure of the Big Five personality traits - neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness - and their facet scales. Neuroticism and extraversion were associated with baseline mood, experienced emotional reactions, and anticipated emotional reactions. The present findings hold implications for the study of individual differences in affective forecasting, personality theory, and interventions research.