Department of Psychiatry
Section Psychopathology of developmental disorders Function
Telephone number: 030-2534582 Supervisor
Prof. dr. Leon Kenemans Title research
Prefrontal modulation of fear: neurobiology and pharmacology Summary research
The neurobiological underpinnings of fear and anxiety have been elucidated extensively in animal models (Davis, 1992; LeDoux, 2000; Walker and Davis, 1997), as well as in human subjects (LaBar, Gatenby, Gore et al., 1998; Morris and Dolan, 2004). The role of various structures included in the limbic system such as the amygdala, hippocampus, brain stem nuclei as the PAG, and ventral prefrontal areas has been highlighted in these and other studies. Higher-order modulation of emotional responding has been suggested to take place in interactions between the midbrain areas of the limbic system on the one hand, and evolutionary newer prefrontal cortical areas.
Concrete analyses of such interactions have been based on animal models (e.g., Morgan and LeDoux, 1999) even though brains of laboratory animals such as rats have only a fraction of the prefrontal tissue in the human brain. Numerous human imaging studies have been devoted to studying the interactions between limbic and prefrontal areas in the regulation of emotion (Hariri, Bookheimer, Mazziotta, 2000). Several authors have suggested that deficits in this circuitry lies at the heart of anxiety disorder (Charney, 2003; Shin, Orr, Carson, et al., 2005; Miller, Taber, Gabbard, et al., 2005). However, not many studies have aimed at the study of online regulation of fear and anxiety responses.
Understanding the role of prefrontal areas underlying phenomena such as inhibition of fear during presentation of safety cues and extinction of fear conditioning is of great practical and clinical interest towards further understanding of individual differences and pathology in fear and anxiety. Just as different anxiety disorders may result from deficits in different parts of the neurobiological network responsible for these phenomena, different pharmacological treatments may interact with dissociable parts of this network. Several pharmacological studies testing anxiolytic drugs with very different mechanisms of action are currently ongoing in (collaboration with) our laboratory. The aim of this PhD project is to extent on these lines of research by furthering insights into the neurobiology of prefrontal modulation of fear and anxiety and more specifically to develop paradigms to study the type and site of action in the brain of pharmacological treatments.