To fear or not to fear: where and how in the brain
Mohammed R Milad, Harvard Medical School

Some people adapt well in the aftermath of traumatic events and are quickly able to inhibit their fear responses to trauma-associated stimuli. Fear responses, however, persist for longer periods of time for others to the point where they reach a pathological state. Why are some people more resilient to trauma while others are not? What are the neural substrates that underlie fear inhibition and extinction? Are these circuits deficient in patients with anxiety disorders? In my talk, I will focus on presenting translational data from the rat and human brains with the objective of trying to provide some preliminary answers to the above stated questions. I will present some data to show that those brain regions in the rat brain appear to be structurally and functionally homologous to specific brain regions in the human brain. I will present some structural and functional neuroimaging and psychophysiological studies done in our lab that focused on the neural mechanisms of fear extinction, particularly extinction recall and the contextual modulation of extinction recall. I will also show data suggesting that these brain regions, the ventromedial prefrontal cortex (vmPFC) and the dorsal anterior cingulate cortex (dACC), appear to be deficient in patients with posttraumatic stress disorder (PTSD). Implications of these findings to the pathophysiology of anxiety disorders such as PTSD and current extinction-based behavioral therapies for anxiety disorders will be discussed.

References:

MR Milad & GJ Quirk (2002), Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 420: 70-74.

MR Milad, BT Quinn, RK Pitman, SP Orr, B Fischl, and SL Rauch (2005), Thickness of ventromedial prefrontal cortex predicts extinction memory. Proceedings of the National Academy of Science, 102: 10706-11.

MR Milad, SP Orr, RK Pitman, SL Rauch (2005), Context modulation of memory for fear extinction in humans. Psychophysiology, 42: 456-464.

MR Milad, CI Wright, SP Orr, RK Pitman, GJ Quirk, and SL Rauch (2007), Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biological Psychiatry, 62: 446-454.

MR Milad, SP Orr, NB Lasko, Y Chang, SL Rauch, and RK Pitman (2008), Presence and Acquired Origin of Reduced Recall for Fear Extinction in PTSD: Results of a Twin Study. Journal of Psychiatric Research, 42: 515-20

DJ Holt, L Lebron-Milad, MR Milad, SL Rauch, RK Pitman, SP Orr, BS Cassidy, JP Walsh, DC Goff, (2009), Extinction memory is impaired in schizophrenia. Biological Psychiatry, 65:455-63

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