The Innate Alarm System and Subliminal Threat Presentation in Posttraumatic Stress Disorder: Neuroimaging of the Midbrain and Cerebellum

Abstract

Background: The innate alarm system, a network of interconnected midbrain, other brainstem, and thalamic structures, serves to rapidly detect stimuli in the environment prior to the onset of conscious awareness. This system is sensitive to threatening stimuli and has evolved to process these stimuli subliminally for hastened responding. Despite the conscious unawareness, the presentation of subliminal threat stimuli generates increased activation of limbic structures, including the amygdala and insula, as well as emotionally evaluative structures, including the cerebellum and orbitofrontal cortex. Posttraumatic stress disorder (PTSD) is associated with an increased startle response and decreased extinction learning to conditioned threat. The role of the innate alarm system in the clinical presentation of PTSD, however, remains poorly understood. Methods: Here, we compare midbrain, brainstem, and cerebellar activation in persons with PTSD (n ¼ 26) and matched controls (n ¼ 20) during subliminal threat presentation. Subjects were presented with masked trauma-related and neutral stimuli below conscious threshold. Contrasts of subliminal brain activation for the presentation of neutral stimuli were subtracted from trauma-related brain activation. Group differences in activation, as well as correlations between clinical scores and PTSD activation, were examined. Imaging data were preprocessed utilizing the spatially unbiased infratentorial template toolbox within SPM12. Results: Analyses revealed increased midbrain activation in PTSD as compared to controls in the superior colliculus, periaqueductal gray, and midbrain reticular formation during subliminal threat as compared to neutral stimulus presentation. Controls showed increased activation in the right cerebellar lobule V during subliminal threat presentation as compared to PTSD. Finally, a negative correlation emerged between PTSD patient scores on the Multiscale Dissociation Inventory for the Depersonalization/Derealization subscale and activation in the right lobule V of the cerebellum during the presentation of subliminal threat as compared to neutral stimuli. Conclusion: We interpret these findings as evidence of innate alarm system overactivation in PTSD and of the prominent role of the cerebellum in the undermodulation of emotion observed in PTSD.

Back to the Basics: Resting State Functional Connectivity of the Reticular Activation System in PTSD and its Dissociative Subtype

“…Deep-layer neuronal circuits that control innate and learned reflexive responses as well as arousal [99][100][101] are becoming increasingly important in the neurobiological conceptualization of PTSD. 1,2,[14][15][16]18,19,[65][66][67][99][100][101][102][103] Crucially, these fundamental neuronal circuits determine the general arousal state of the organism, laying the foundation for reflexive actions. 26 The present investigation provides novel evidence that as compared to both control subjects and individuals with PTSD, participants with PTSDþDS showed stronger rsFC of the PPN with the amygdala, the parahippocampal gyrus, the anterior cingulate cortex, and the ventromedial prefrontal cortex.…”

“…5,[46][47][48][49][50][51][52][53][54][55][56] Importantly, recent studies emphasize sensitization, particularly in innate threat processing-related brain regions in PTSD, where the presentation of subliminal threat cues elicited stronger activation in the brainstem, the midbrain, the amygdala, and the parahippocampal gyrus in individuals with PTSD as compared to healthy trauma-and non-trauma-exposed controls. 5,[57][58][59][60][61][62][63] Despite emerging evidence of altered states of arousal, and the sensitization of innate threat processing in PTSD during symptom provocation and resting state, 1,2,5,43,44,[57][58][59][60][61][62][64][65][66][67] research examining connectivity of the RAS to subcortical and to cortical brain structures remains in its nascent stages. Accordingly, we sought to delineate resting state functional connectivity (rsFC) patterns of a main component of the RAS, the pedunculopontine nuclei (PPN), 39,[68][69][70][71][72][73][74]…”

The Threatful Self: Midbrain Functional Connectivity to Cortical Midline and Parietal Regions During Subliminal Trauma-Related Processing in PTSD

“…The analyses discussed in this article are novel; however, the data generated on this sample are analyzed in our other published works. 27,29,48,49 The exclusion criteria for participation in the study included incompatibilities with the scanning requirements, previous neurologic and development illness, comorbid schizophrenia or bipolar disorder, alcohol or substance abuse within six months prior to scanning, a history of head trauma, or pregnancy during the time of the scan. Diagnoses were determined using the Clinician Administered PTSD Scale (CAPS) 50 and confirmed by a Structured Clinical Interview for DSM-IV Axis-I disorders.…”

“…20 Notably, several structures associated with the IAS display overactivation during the presentation of fear-or trauma-related material in PTSD, including the amygdala, [21][22][23] the parahippocampal gyrus, 24,25 the lower brainstem, 26,27 and the PAG. 26,28,29 Critically, this pattern of neural response emerges under conditions of subliminal and of supraliminal presentation. 21,26,27 In particular, a recent study by Terpou et al 29 revealed a cluster of significantly greater activation of the PAG, as compared to controls, in participants with PTSD during the subliminal presentation of trauma-related word stimuli-to which the present report builds on these findings.…”

“…26,28,29 Critically, this pattern of neural response emerges under conditions of subliminal and of supraliminal presentation. 21,26,27 In particular, a recent study by Terpou et al 29 revealed a cluster of significantly greater activation of the PAG, as compared to controls, in participants with PTSD during the subliminal presentation of trauma-related word stimuli-to which the present report builds on these findings.…”