Functional Neuroanatomy of Human Fear Conditioning

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Multiple neural systems exist within the human brain that allow us to learn and remember. At the present time it is not entirely clear how the many different forms of human memory relate directly to structures and circuits in the brain. The long-term goals of this study are to understand the neural mechanisms of a specific form of memory, aversive Pavlovian conditioning, in human subjects. The ability to learn associations through Pavlovian conditioning is shared by a wide variety of organisms but very little is known about the neurobiological substrates of this process in humans. Our general approach is to use state of the art whole brain functional magnetic resonance imaging (fMRI) to describe brain regions and circuits that contribute to the acquisition and performance of fear conditioning. Functional maps of brain areas in which activity is directly related to exposure to the CS+ or CS- in a differential conditioning paradigm will be constructed. Similar techniques will be used to characterize brain areas in which activity is best related to autonomic fear responses versus cognitive awareness of the relationship between programmed stimuli. We will observe how these functional maps change during extinction of the conditioned response and during reversal training after successful discrimination. We will map whole brain functional activity during trace conditioning with several inter-stimulus intervals to determine if unique brain areas are active in this paradigm as would be predicted from the laboratory animal literature. The project will focus on a series of predictions regarding the roles of the amygdala, hippocampus, prefrontal cortex, and anterior cingulate cortex based on current knowledge from laboratory animal studies and other memory paradigms used in human brain imaging. In all cases an extensive multi-stage analysis of the fMRI data is proposed in which we will assess event-related patterns of activity related to target stimuli and responses. The results will enable very significant advancement in understanding; 1) the relationship between declarative and procedural memory systems, 2) the role of awareness in learning, 3) the comparative neuroanatomy of memory, and 4) the brain mechanisms of Pavlovian conditioning. These data will be of great value when interpreting memory deficits in patients with brain damage due to disease or trauma.