Intrinsic sensory disinhibition contributes to intrusive re-experiencing in combat veterans

Abstract

Word count -Main Text: 3585 (no citations) Word count -Abstract: 225 Number of Figures: 5 Number of Tables: 1 Clancy et al. Sensory disinhibition and intrusive re-experiencing 2 HIGHLIGHTS • Alpha oscillations (indexing sensory inhibition) measured in 86 combat veterans • Re-experiencing symptom severity was associated with attenuated alpha connectivity • Trauma memory for, not emotional response to, odors mediated this relationship • Trauma memories may arise via disinhibited activation of sensory representations • Sensory systems may be novel target for intrusive re-experiencing symptom treatment Clancy et al. Sensory disinhibition and intrusive re-experiencing 3 ABSTRACTIntrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder (PTSD). In contrast to abstract, verbal intrusions in other affective disorders, intrusive re-experiencing in PTSD is characterized by vivid sensory details as "flashbacks". While prevailing PTSD models largely focus on dysregulated emotional processes, we hypothesize that deficient sensory inhibition in PTSD could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions of trauma. In 86 combat veterans, we examined resting-state alpha (8-12 Hz) oscillatory activity (in both power and posteriorfrontal connectivity), given its key role in sensory cortical inhibition, in association with intrusive reexperiencing symptoms. A subset (N = 35) of veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed a strong association between intrusive re-experiencing symptoms and attenuated resting-state posteriorfrontal alpha connectivity, which were both correlated with olfactory trauma memory (but not emotional response). Importantly, olfactory trauma memory was further identified as a full mediator of the relationship between alpha connectivity and intrusive re-experiencing in these veterans, suggesting that deficits in intrinsic sensory inhibition can contribute to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and spontaneously activating sensory representations of trauma, impaired sensory inhibition can constitute a sensory mechanism of intrusive re-experiencing in PTSD.

Traces of Trauma: A Multivariate Pattern Analysis of Childhood Trauma, Brain Structure, and Clinical Phenotypes

“…Second, associations with the DLPFC, the insula and the cingulate gyrus relate emotional trauma to key brain systems subserving emotional processing (68)(69)(70), memory formation (71,72) and risk for psychiatric disorders (73)(74)(75). These findings support the hypothesis that trauma experience is connected to sensory and perceptive dysregulations, which could also be accessed therapeutically (76)(77)(78).…”

Posttraumatic Stress Disorder Is Associated with α Dysrhythmia across the Visual Cortex and the Default Mode Network

“…As mentioned above, alpha oscillations also play a role in long-range neural communication and resting-state alpha power correlates positively with DMN activity (Mantini et al, 2007;Jann et al, 2009;Sadaghiani et al, 2010;Knyazev et al, 2011;Mo et al, 2013;Samogin et al, 2019). The alpha deficits in DMN hubs thus dovetails the extant literature citing both deficient alpha activity (Clancy et al, 2017;Clancy et al, 2020) and DMN hypoactivity in PTSD (Koch et al, 2016;Akiki et al, 2018). Notably, resting-state beta and theta oscillations have also been found to be associated with DMN activity (Laufs et al, 2003;Mantini et al, 2007;Scheeringa et al, 2012).…”

“…Together, current findings implicate a core visual-cortex-DMN system of alpha dysrhythmia in PTSD. The critical role of visual cortical alpha deficits in this pathology lends credence to a sensory hypothesis of PTSD centered on sensory cortical disinhibition (Clancy et al, 2017;Li, 2019;Clancy et al, 2020) and bottom-up accounts of PTSD in general (Nicholson et al, 2017;Badura-Brack et al, 2018). Childhood trauma, a common PTSD risk factor, has been associated with various aberrations in the sensory cortex and sensory pathway (Teicher et al, 2016), adding to the support for this sensory hypothesis.…”

“…Aberrant alpha oscillations have been featured in a "thalamocortical dysrhythmia" model of neuropsychiatric disorders (Llinas et al, 1999;Schulman et al, 2011), which are conceptualized transdiagnostically as oscillopathies (Basar, 2013;Buzsaki et al, 2013). Reduced resting-state alpha activity has been observed in patients with PTSD (vs. healthy controls and patients with generalized anxiety disorder/GAD) (Clancy et al, 2017) and combat veterans with severe symptoms (Clancy et al, 2020). Given the demonstrated association between alpha oscillations and DMN activity, we hypothesized that PTSD is associated with deficient alpha activity in the DMN and deficient inhibition of sensory cortical input to the DMN.…”

Transcranial stimulation of alpha oscillations upregulates the default mode network

“…E ) Violin plots for alpha power over left and right electrodes indicate significant right posterior power increase in the Active group. F ) Right hemisphere posterior→frontal (P→F) Granger causality (GC) waveforms demonstrate specific increases in the Active (vs. Sham) group, which were restricted to the alpha frequency (grey box); the red bar indicates frequency bins (0.5 Hz each) showing significant tACS effects; the inset shows ipsilateral electrode pairs used for alpha GC as used in our prior studies (27, 59, 60); Ribbon = SEM. G ) Violin plots for alpha-frequency P→F GC in the left and right hemispheres indicate significant right hemispheric GC increase in the Active group.…”