Imaging Unconditioned Fear

Summary

Principal Investigator: Jean King
Abstract: The application of functional magnetic resonance imaging (fMRI) to visualize brain regions involved in emotion has considerably improved our understanding of human neurobiology. Progress has been much slower in applying this approach to conscious animals, due to obstacles such as immobility in the magnet and ability to perform tasks within a dark, narrow, horizontal space. These obstacles have been overcome with the recent invention of a small animal holding device for performing fMRI on fully awake rodents ranging in weight from 300 - 500g. Since fMRI research paradigms can now be performed in animals without injury or sacrifice, they provide new research opportunities for studies in areas where multiple time points in brain functioning can be assessed non-invasively, thereby allowing spatial as well as temporal mapping. This proposal describes a novel approach for mapping the fear response in the anaesthetized rat with fMRI. These studies will use fMRI to identify and monitor neuronal activation associated with fearfulness. For most animals, a primary fear-eliciting event is the possibility of being attacked by a predator. Consequently, predator stress is currently being simulated under laboratory conditions to trigger unconditioned (innate) fear responses in animals. Recent reports suggest that changes in neuroendocrine status of an animal may be central to fear response. In addition, drug intervention strategies have pointed to the inherent plasticity of the neural systems underlying this emotion. To test the hypothesis that unconditioned fear triggered by the scent of a predator will result in alterations in neuronal activation in a manner that reflect the neuroendocrine status and pharmacological response of an animal, we will utilize the technological advances for performing fMRI non-invasively in a conscious animal. The long-term goal of this research is to provide an understanding of the unique features of central mechanisms that regulate fearfulness and the impact of the neuroendocrine and neuropharmacological status on the processing of this emotion. Since fear experience by all animals, these studies may expand our understanding of anxiety and phobias in general.
Funding Period: 2002-12-06 - 2007-11-30
more information: NIH RePORT

Top Publications

  1. ncbi Amygdala-orbitofrontal resting-state functional connectivity is associated with trait anger
    CARL E FULWILER
    Department of Psychiatry, Center for Mental Health Services Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Neuroreport 23:606-10. 2012
  2. ncbi The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD
    Pallavi Rane
    Center for Comparative NeuroImaging, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Neuropharmacology 62:2409-12. 2012
  3. pmc Anticorrelated resting-state functional connectivity in awake rat brain
    Zhifeng Liang
    Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Neuroimage 59:1190-9. 2012
  4. pmc Uncovering intrinsic connectional architecture of functional networks in awake rat brain
    Zhifeng Liang
    Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Neurosci 31:3776-83. 2011
  5. pmc Fear induced neuronal alterations in a genetic model of depression: an fMRI study on awake animals
    Wei Huang
    Center for Comparative NeuroImaging, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01605, USA
    Neurosci Lett 489:74-8. 2011
  6. pmc Mapping resting-state brain networks in conscious animals
    Nanyin Zhang
    Center for Comparative NeuroImaging CCNI, Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, United States
    J Neurosci Methods 189:186-96. 2010
  7. pmc Oxytocin modulates unconditioned fear response in lactating dams: an fMRI study
    Marcelo Febo
    Center for Translational Neuroimaging and Department of Psychology, Northeastern University, Boston, MA, USA
    Brain Res 1302:183-93. 2009
  8. pmc Female fear: influence of estrus cycle on behavioral response and neuronal activation
    Wei Chen
    Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Behav Brain Res 201:8-13. 2009
  9. ncbi The role of 5-HT1A receptors in the behavioral responses associated with innate fear
    Jessica Shields
    University of Massachusetts Medical School, Department of Psychiatry, Center for Comparative NeuroImaging, 55 Lake Avenue North, Worcester, MA 01655, USA
    Behav Neurosci 122:611-7. 2008
  10. ncbi Imaging brain activation in nicotine-sensitized rats
    Zhixin Li
    Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Brain Res 1199:91-9. 2008

Scientific Experts

  • Jean King
  • Nanyin Zhang
  • Jessica Shields
  • Zhifeng Liang
  • Wei Chen
  • Wei Huang
  • Zhixin Li
  • CARL E FULWILER
  • Pallavi Rane
  • Marcelo Febo
  • Praveen Kulkarni
  • Schahram Akbarian
  • Yin Guo
  • Meghan Heffernan
  • David H Overstreet
  • Meghan E Heffernan
  • Craig F Ferris
  • Robert J Wellman
  • Joseph R DiFranza
  • Jeff Tenney

Detail Information

Publications13

  1. ncbi Amygdala-orbitofrontal resting-state functional connectivity is associated with trait anger
    CARL E FULWILER
    Department of Psychiatry, Center for Mental Health Services Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Neuroreport 23:606-10. 2012
    ..Our findings also suggest that RSFC may prove valuable as a trait marker for disorders characterized by emotional dysregulation such as depression, anxiety, and personality disorders...
  2. ncbi The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD
    Pallavi Rane
    Center for Comparative NeuroImaging, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Neuropharmacology 62:2409-12. 2012
    ..The results indicated that the sodium butyrate treatment not only effectively alleviated the set-shifting deficits, but also improved the attentional set formation in the treated rats...
  3. pmc Anticorrelated resting-state functional connectivity in awake rat brain
    Zhifeng Liang
    Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Neuroimage 59:1190-9. 2012
    ..In addition, combining the neurobiological data of the IL-amygdala circuit in rodents, the finding of the present study will enable further investigation of the neurobiological basis underlying anticorrelation...
  4. pmc Uncovering intrinsic connectional architecture of functional networks in awake rat brain
    Zhifeng Liang
    Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Neurosci 31:3776-83. 2011
    ....
  5. pmc Fear induced neuronal alterations in a genetic model of depression: an fMRI study on awake animals
    Wei Huang
    Center for Comparative NeuroImaging, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01605, USA
    Neurosci Lett 489:74-8. 2011
    ..These results are evidence for the value of translational models of depression in expanding understanding of the neural circuitries sub-serving common human co-morbidities like depression and fear...
  6. pmc Mapping resting-state brain networks in conscious animals
    Nanyin Zhang
    Center for Comparative NeuroImaging CCNI, Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, United States
    J Neurosci Methods 189:186-96. 2010
    ....
  7. pmc Oxytocin modulates unconditioned fear response in lactating dams: an fMRI study
    Marcelo Febo
    Center for Translational Neuroimaging and Department of Psychology, Northeastern University, Boston, MA, USA
    Brain Res 1302:183-93. 2009
    ....
  8. pmc Female fear: influence of estrus cycle on behavioral response and neuronal activation
    Wei Chen
    Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Behav Brain Res 201:8-13. 2009
    ..Taken together, these results suggest that the female's hormonal status may be correlated with alterations in both neuronal and behavioral indices of fear...
  9. ncbi The role of 5-HT1A receptors in the behavioral responses associated with innate fear
    Jessica Shields
    University of Massachusetts Medical School, Department of Psychiatry, Center for Comparative NeuroImaging, 55 Lake Avenue North, Worcester, MA 01655, USA
    Behav Neurosci 122:611-7. 2008
    ..Taken together, these results suggest an additional anxyolitic-like effect of 8-OHDPAT in innate fear paradigms...
  10. ncbi Imaging brain activation in nicotine-sensitized rats
    Zhixin Li
    Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Brain Res 1199:91-9. 2008
    ....
  11. ncbi Imaging unconditioned fear response with manganese-enhanced MRI (MEMRI)
    Wei Chen
    University of Massachusetts Medical School, Department of Psychiatry, Center for Comparative NeuroImaging, 55 Lake Avenue North, Worcester, MA 01655, USA
    Neuroimage 37:221-9. 2007
    ..Therefore the current study support the validity of MEMRI in the exploration of highly relevant complex neural circuitries associated with cognition and emotion...
  12. pmc Procedure for minimizing stress for fMRI studies in conscious rats
    Jean A King
    Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical Center, Worcester, MA 01655, USA
    J Neurosci Methods 148:154-60. 2005
    ..The feasibility of improving the quality of fMRI data acquired in alert rats by utilizing a relatively simple technique is presented...
  13. ncbi Deficits in testosterone facilitate enhanced fear response
    Jean A King
    Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Psychoneuroendocrinology 30:333-40. 2005
    ..These studies suggest that testosterone decline may have a significant effect on increasing innate fear response and fear-induced enhancement of analgesia in male rats...