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The Journal of Neuroscience, June 6, 2007, 27(23):6313-6319; doi:10.1523/JNEUROSCI.5369-06.2007

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Behavioral/Systems/Cognitive
Cerebral Blood Flow in Immediate and Sustained Anxiety

Gregor Hasler,¹ Stephen Fromm,² Ruben P. Alvarez,² David A. Luckenbaugh,² Wayne C. Drevets,² and Christian Grillon²

¹Psychiatric University Hospital, 8091 Zurich, Switzerland, and ²Mood and Anxiety Disorders Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892

Correspondence should be addressed to Dr. Gregor Hasler, National Institutes of Health, National Institute of Mental Health, Mood and Anxiety Disorders Program, 15K North Drive, Room 200, MSC 2670, Bethesda, MD 20892-2670. Email: g.hasler{at}bluewin.ch

The goal of this study was to compare cerebral blood flow (CBF) changes associated with phasic cued fear versus those associated with sustained contextual anxiety. Positron emission tomography images of CBF were acquired using [O-15]H₂O in 17 healthy human subjects as they anticipated unpleasant electric shocks that were administered predictably (signaled by a visual cue) or unpredictably (threatened by the context). Presentation of the cue in either threat condition was associated with increased CBF in the left amygdala. A cue that specifically predicted the shock was associated with CBF increases in the ventral prefrontal cortex (PFC), hypothalamus, anterior cingulate cortex, left insula, and bilateral putamen. The sustained threat context increased CBF in the right hippocampus, mid-cingulate gyrus, subgenual PFC, midbrain periaqueductal gray, thalamus, bilateral ventral striatum, and parieto-occipital cortex. This study showed distinct neuronal networks involved in cued fear and contextual anxiety underlying the importance of this distinction for studies on the pathophysiology of anxiety disorders.

Key words: fear; anxiety; amygdala; hippocampus; context; cerebral blood flow

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Received Dec. 13, 2006; revised April 30, 2007; accepted April 30, 2007.

Correspondence should be addressed to Dr. Gregor Hasler, National Institutes of Health, National Institute of Mental Health, Mood and Anxiety Disorders Program, 15K North Drive, Room 200, MSC 2670, Bethesda, MD 20892-2670. Email: g.hasler{at}bluewin.ch

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