Restless 'rest': intrinsic sensory hyperactivity and disinhibition in post-traumatic stress disorder

Brain. 2017 Jul 1;140(7):2041-2050. doi: 10.1093/brain/awx116.


Post-traumatic stress disorder is characterized by exaggerated threat response, and theoretical accounts to date have focused on impaired threat processing and dysregulated prefrontal-cortex-amygdala circuitry. Nevertheless, evidence is accruing for broad, threat-neutral sensory hyperactivity in post-traumatic stress disorder. As low-level, sensory processing impacts higher-order operations, such sensory anomalies can contribute to widespread dysfunctions, presenting an additional aetiological mechanism for post-traumatic stress disorder. To elucidate a sensory pathology of post-traumatic stress disorder, we examined intrinsic visual cortical activity (based on posterior alpha oscillations) and bottom-up sensory-driven causal connectivity (Granger causality in the alpha band) during a resting state (eyes open) and a passive, serial picture viewing state. Compared to patients with generalized anxiety disorder (n = 24) and healthy control subjects (n = 20), patients with post-traumatic stress disorder (n = 25) demonstrated intrinsic sensory hyperactivity (suppressed posterior alpha power, source-localized to the visual cortex-cuneus and precuneus) and bottom-up inhibition deficits (reduced posterior→frontal Granger causality). As sensory input increased from resting to passive picture viewing, patients with post-traumatic stress disorder failed to demonstrate alpha adaptation, highlighting a rigid, set mode of sensory hyperactivity. Interestingly, patients with post-traumatic stress disorder also showed heightened frontal processing (augmented frontal gamma power, source-localized to the superior frontal gyrus and dorsal cingulate cortex), accompanied by attenuated top-down inhibition (reduced frontal→posterior causality). Importantly, not only did suppressed alpha power and bottom-up causality correlate with heightened frontal gamma power, they also correlated with increased severity of sensory and executive dysfunctions (i.e. hypervigilance and impulse control deficits, respectively). Therefore, sensory aberrations help construct a vicious cycle in post-traumatic stress disorder that is in action even at rest, implicating dysregulated triangular sensory-prefrontal-cortex-amygdala circuitry: intrinsic sensory hyperactivity and disinhibition give rise to frontal overload and disrupt executive control, fuelling and perpetuating post-traumatic stress disorder symptoms. Absent in generalized anxiety disorder, these aberrations highlight a unique sensory pathology of post-traumatic stress disorder (ruling out effects merely reflecting anxious hyperarousal), motivating new interventions targeting sensory processing and the sensory brain in these patients.

Keywords: Granger causality; alpha/gamma oscillations; post-traumatic stress disorder (PTSD); resting state; sensory hyperactivity.

MeSH terms

  • Adult
  • Alpha Rhythm / physiology
  • Anxiety Disorders / physiopathology
  • Case-Control Studies
  • Executive Function / physiology
  • Female
  • Frontal Lobe / physiopathology
  • Gamma Rhythm / physiology
  • Gyrus Cinguli / physiopathology
  • Humans
  • Male
  • Neural Inhibition / physiology*
  • Photic Stimulation
  • Rest / physiology*
  • Sensation Disorders / complications
  • Sensation Disorders / physiopathology*
  • Stress Disorders, Post-Traumatic / complications
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Visual Cortex / physiopathology*
  • Visual Perception / physiology
  • Young Adult