Evidence for coordinated functional activity within the extended amygdala of non-human and human primates

Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA.
NeuroImage (Impact Factor: 6.13). 03/2012; 61(4):1059-66. DOI: 10.1016/j.neuroimage.2012.03.045
Source: PubMed

ABSTRACT Neuroanatomists posit that the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST) comprise two major nodes of a macrostructural forebrain entity termed the extended amygdala. The extended amygdala is thought to play a critical role in adaptive motivational behavior and is implicated in the pathophysiology of maladaptive fear and anxiety. Resting functional connectivity of the Ce was examined in 107 young anesthetized rhesus monkeys and 105 young humans using standard resting-state functional magnetic resonance imaging (fMRI) methods to assess temporal correlations across the brain. The data expand the neuroanatomical concept of the extended amygdala by finding, in both species, highly significant functional coupling between the Ce and the BST. These results support the use of in vivo functional imaging methods in nonhuman and human primates to probe the functional anatomy of major brain networks such as the extended amygdala.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate. Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain regions underlies primates' capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex, a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.Molecular Psychiatry advance online publication, 27 May 2014; doi:10.1038/mp.2014.46.
    Molecular Psychiatry 05/2014; 19(8). DOI:10.1038/mp.2014.46 · 15.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Dysfunction in ventromedial prefrontal cortex (vmPFC) is believed to play a pivotal role in the pathogenesis of mood and anxiety disorders. Leading neurocircuitry models of these disorders propose that hypoactivity in vmPFC engenders disinhibited amygdala activity, and consequently, pathologically elevated levels of negative affect. This model predicts that a selective loss or diminution of vmPFC function would result in heightened amygdala activity. While this prediction has been borne out in rodent lesion and electrophysiological studies using fear conditioning and extinction paradigms, there has not yet been a definitive test of this prediction in humans. Methods In this study, we tested this prediction through a novel use of fMRI in n=4 neurosurgical patients with focal, bilateral vmPFC damage. Results Relative to neurologically healthy comparison subjects, the vmPFC lesion patients exhibited potentiated amygdala responses to aversive images as well as elevated rest-state amygdala functional connectivity. We observed no comparable group differences for activity in other brain regions. Conclusions These results provide unique evidence for the critical role of vmPFC in regulating amygdala activity in humans, and help elucidate the causal neural interactions that underlie mental illness.
    Biological Psychiatry 02/2014; DOI:10.1016/j.biopsych.2014.02.014 · 9.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates' biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 09/2014; 55(2):333-46. DOI:10.1093/ilar/ilu019 · 1.05 Impact Factor


Available from
May 16, 2014