The Journal of Neuroscience, May 30, 2007, 27(22):5958-5966; doi:10.1523/JNEUROSCI.5218-06.2007
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Behavioral/Systems/Cognitive
Processing of Temporal Unpredictability in Human and Animal Amygdala
Cyril Herry,1 *
Dominik R. Bach,2 *
Fabrizio Esposito,3
Francesco Di Salle,4,5
Walter J. Perrig,6
Klaus Scheffler,7
Andreas Lüthi,1 and
Erich Seifritz2,8
1Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland, 2University Hospital of Psychiatry Bern, 3000 Bern, Switzerland, 3Department of Neurological Sciences, University of Naples Federico II, 80127 Naples, Italy, 4Department of Neuroscience, University of Pisa, 56126 Pisa, Italy, 5Department of Cognitive Neuroscience, University of Maastricht, 6200 Maastricht, The Netherlands, 6Institute of Psychology, University of Bern, 3000 Bern, Switzerland, 7MR Physics, Department of Medical Radiology, University of Basel, 4031 Basel, Switzerland, and 8Department of Psychiatry, University of Basel, 4025 Basel, Switzerland
Correspondence should be addressed to either of the following: Dr.Andreas Lüthi, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland, Email: andreas.luthi{at}fmi.ch; or Dr. Erich Seifritz, University Hospital of Psychiatry Bern, Bolligenstrasse 111, CH-3000 Bern, Switzerland, E-mail: Email: seifritz{at}puk.unibe.ch
The amygdala has been studied extensively for its critical role in associative fear conditioning in animals and humans. Noxious stimuli, such as those used for fear conditioning, are most effective in eliciting behavioral responses and amygdala activation when experienced in an unpredictable manner. Here, we show, using a translational approach in mice and humans, that unpredictability per se without interaction with motivational information is sufficient to induce sustained neural activity in the amygdala and to elicit anxiety-like behavior. Exposing mice to mere temporal unpredictability within a time series of neutral sound pulses in an otherwise neutral sensory environment increased expression of the immediate-early gene c-fos and prevented rapid habituation of single neuron activity in the basolateral amygdala. At the behavioral level, unpredictable, but not predictable, auditory stimulation induced avoidance and anxiety-like behavior. In humans, functional magnetic resonance imaging revealed that temporal unpredictably causes sustained neural activity in amygdala and anxiety-like behavior as quantified by enhanced attention toward emotional faces. Our findings show that unpredictability per se is an important feature of the sensory environment influencing habituation of neuronal activity in amygdala and emotional behavior and indicate that regulation of amygdala habituation represents an evolutionary-conserved mechanism for adapting behavior in anticipation of temporally unpredictable events.
Key words: unpredictability; amygdala; anxiety; avoidance; habituation; fMRI
Received Dec. 2, 2006;
revised April 26, 2007;
accepted April 26, 2007.
Correspondence should be addressed to either of the following: Dr.Andreas Lüthi, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland, Email: andreas.luthi{at}fmi.ch; or Dr. Erich Seifritz, University Hospital of Psychiatry Bern, Bolligenstrasse 111, CH-3000 Bern, Switzerland, E-mail: Email: seifritz{at}puk.unibe.ch
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