Elsevier

Biological Psychiatry

Volume 82, Issue 6, 15 September 2017, Pages 447-454
Biological Psychiatry

Archival Report
The Unpredictive Brain Under Threat: A Neurocomputational Account of Anxious Hypervigilance

https://doi.org/10.1016/j.biopsych.2017.06.031Get rights and content

Abstract

Background

Anxious hypervigilance is marked by sensitized sensory-perceptual processes and attentional biases to potential danger cues in the environment. How this is realized at the neurocomputational level is unknown but could clarify the brain mechanisms disrupted in psychiatric conditions such as posttraumatic stress disorder. Predictive coding, instantiated by dynamic causal models, provides a promising framework to ground these state-related changes in the dynamic interactions of reciprocally connected brain areas.

Methods

Anxiety states were elicited in healthy participants (n = 19) by exposure to the threat of unpredictable, aversive shocks while undergoing magnetoencephalography. An auditory oddball sequence was presented to measure cortical responses related to deviance detection, and dynamic causal models quantified deviance-related changes in effective connectivity. Participants were also administered alprazolam (double-blinded, placebo-controlled crossover) to determine whether the cortical effects of threat-induced anxiety are reversed by acute anxiolytic treatment.

Results

Deviant tones elicited increased auditory cortical responses under threat. Bayesian analyses revealed that hypervigilant responding was best explained by increased postsynaptic gain in primary auditory cortex activity as well as modulation of feedforward, but not feedback, coupling within a temporofrontal cortical network. Increasing inhibitory gamma-aminobutyric acidergic action with alprazolam reduced anxiety and restored feedback modulation within the network.

Conclusions

Threat-induced anxiety produced unbalanced feedforward signaling in response to deviations in predicable sensory input. Amplifying ascending sensory prediction error signals may optimize stimulus detection in the face of impending threats. At the same time, diminished descending sensory prediction signals impede perceptual learning and may, therefore, underpin some of the deleterious effects of anxiety on higher-order cognition.

Section snippets

Subjects

Nineteen healthy participants (7 women, mean age ± SD = 29 ± 7 years) completed two testing MEG sessions and a single magnetic resonance imaging (MRI) session. Target sample size was based on previously published data using the same MEG paradigm (9). All participants received physical and psychiatric exams to ensure their health status and confirm that they were not taking psychoactive medications. They were also screened for metallic implants and other contraindications associated with MRI

Contextual and Pharmacological Manipulation of Anxiety

Participants were exposed to two conditions during MEG scanning, a threat context in which aversive shocks could be delivered unpredictably without immediate warning and a safe context in which no shocks could be delivered. MEG scanning commenced approximately 90 to 120 minutes after participants had been orally administered 1 mg of the benzodiazepine alprazolam or an inactive placebo on two separate occasions (double blinded). As expected, participants reported feeling less anxious during the

Discussion

By exposing participants in a threat-induced anxiety state to simple auditory oddball stimuli, we observed a radical change in network dynamics underlying early perceptual processing. Within a DCM analytic framework, Bayesian model comparisons revealed that deviant stimulus responding under threat of shock could be adequately explained by changes only in intrinsic A1 gain and feedforward signaling within a bilateral temporofrontal cortical network. In other words, models that allowed for

Acknowledgments and Disclosures

This work was supported in part by the Intramural Research Program of the National Institute of Mental Health Grant No. ZIAMH002798 (Protocol 02-M-0321; NCT00047853 to CG), a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation (to BRC), and a University of Queensland Fellowship Grant No. 2016000071 (to MIG).

We thank Lynne Liebermann for assistance with data collection, members of the National Institute of Mental Health Magnetoencephalography Core Facility for quality

References (51)

  • S.J. Kiebel et al.

    Dynamic causal modelling of evoked responses: The role of intrinsic connections

    Neuroimage

    (2007)
  • C. Grillon et al.

    The benzodiazepine alprazolam dissociates contextual fear from cued fear in humans as assessed by fear-potentiated startle

    Biol Psychiatry

    (2006)
  • K. Friston

    The free-energy principle: A rough guide to the brain?

    Trends Cogn Sci

    (2009)
  • J.M.P. Baas et al.

    Brainstem correlates of defensive states in humans

    Biol Psychiatry

    (2006)
  • R.W. Cox

    AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages

    Comput Biomed Res

    (1996)
  • K.E. Stephan et al.

    Ten simple rules for dynamic causal modelling

    Neuroimage

    (2010)
  • O. David et al.

    Dynamic causal modelling of evoked responses in EEG and MEG

    Neuroimage

    (2006)
  • O. David et al.

    A neural mass model for MEG/EEG: Coupling and neuronal dynamics

    Neuroimage

    (2003)
  • S. Lissek et al.

    Classical fear conditioning in the anxiety disorders: A meta-analysis

    Behav Res Ther

    (2005)
  • B.R. Cornwell et al.

    Anxiety, a benefit and detriment to cognition: Behavioral and magnetoencephalographic evidence from a mixed-saccade task

    Brain Cogn

    (2012)
  • C. Grillon et al.

    Increased anxiety during anticipation of unpredictable aversive stimuli in posttraumatic stress disorder but not in generalized anxiety disorder

    Biol Psychiatry

    (2009)
  • Y. Chang et al.

    Mismatch negativity indices of enhanced preattentive automatic processing in panic disorder as measured by a multi-feature paradigm

    Biol Psychol

    (2015)
  • D.W. Grupe et al.

    Uncertainty and anticipation in anxiety: An integrated neurobiological and psychological perspective

    Nat Rev Neurosci

    (2013)
  • O.J. Robinson et al.

    Stress increases aversive prediction error signal in the ventral striatum

    Proc Natl Acad Sci U S A

    (2013)
  • A.J. Shackman et al.

    Stress potentiates early and attenuates late stages of visual processing

    J Neurosci

    (2011)
  • Cited by (53)

    View all citing articles on Scopus
    View full text