Dynamic causal modeling in PTSD and its dissociative subtype: Bottom–up versus top–down processing within fear and emotion regulation circuitry
Open accessAbstract
Objective: Posttraumatic stress disorder (PTSD) is associated with decreased top–down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top–down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. Methods: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting‐state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [ n = 62]; PTSD + DS [ n = 41]; age‐matched healthy trauma‐unexposed controls [ n = 52]). Results: PTSD was characterized by a pattern of predominant bottom–up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top–down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. Conclusions: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper‐ vs. hypo‐emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom–up defensive fear processing versus enhanced top–down regulation. Hum Brain Mapp 38:5551–5561, 2017 . © 2017 Wiley Periodicals, Inc.
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Greater activity in prefrontal cortex was associated with subjective feelings of dissociation across various emotionally provocative tasks.
“Similarly, greater activity in prefrontal cortex was associated with subjective feelings of dissociation (e.g., depersonalization/derealization) across various emotionally provocative tasks [147–149].”
From Treatment of dissociative identity disorder: leveraging neurobiology to optimize success (2024) · cites this paper as [148]
The Introduction (page unavailable) describes increased medial prefrontal activation in dissociative-subtype PTSD during symptom provocation, alongside emotional detachment. But the paper’s own scan was conducted at rest; it does not establish an association between prefrontal activity and subjective dissociation across various emotionally provocative tasks. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIndividuals with the dissociative subtype of PTSD have greater activity in regions associated with top-down regulation and diminished activity in limbic regions when presented with emotionally provocative autobiographical trauma-related scripts.
“prior work indicates that individuals with the dissociative subtype of PTSD have greater activity in regions associated with “top-down” regulation (e.g., prefrontal cortex) and diminished activity in limbic regions (e.g., amygdala) when presented with emotionally provocative autobiographical trauma-related scripts [147,148].”
From Treatment of dissociative identity disorder: leveraging neurobiology to optimize success (2024) · cites this paper as [148]
The Introduction describes increased medial prefrontal regulatory activation and reduced amygdala activation in dissociative-subtype PTSD during symptom provocation. It does not specify autobiographical trauma-related scripts, and the Methods describe this paper’s own scan as eyes-closed resting state rather than script presentation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredWhen the prefrontal cortex is shutdown among individuals with classic PTSD, it can propagate an emotion under-modulation symptom profile, including hypervigilance and hyperarousal symptoms.
“Specifically, when the prefrontal cortex is shutdown among individuals with classic PTSD, it can propagate an emotion under-modulation symptom profile, which includes hypervigilance and hyperarousal symptoms.”
From How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD (2021) · cites this paper as Nicholson et al., 2017
The Introduction (page not provided) describes classic PTSD as emotion undermodulation associated with decreased medial prefrontal regulatory activation and hyperarousal. It also links PTSD threat circuitry to hypervigilant tendencies. But the paper says prefrontal regulation is decreased, not that the prefrontal cortex is shut down; the Amygdala Connections with the vmPFC section reports some top-down connections in the PTSD group. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThis provides further data supporting a model of enhanced top-down emotional over-regulation with significant dissociation, in contrast to decreased emotion regulation in the majority of PTSD cases.
“The authors suggest that this provides further data supporting a model of enhanced top-down, emotional over-regulation with significant dissociation, in contrast to decreased emotion regulation in the majority of PTSD cases.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [171]
Nicholson et al. found that PTSD without dissociation was characterized primarily by bottom-up connectivity from the amygdala to the vmPFC, whereas PTSD with dissociation had predominant top-down connectivity from the vmPFC to the amygdala.
“Nicholson et al. [171] found that PTSD without dissociation was characterized primarily by ‘bottom-up connectivity’ from the amygdala to the vmPFC, whereas PTSD with dissociation had predominant ‘top-down connectivity’ from the vmPFC to the amygdala.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [171]
Simultaneously the heart rate, blood pressure and skeletal muscle tone go down (tonic immobility), which may be mediated by increased top-down modulation of limbic brain regions including the amygdala and periaqueductal gray.
“Simultaneously the heart rate, blood pressure and skeletal muscle tone go down (tonic immobility) (McKinnon et al., 2016), which may be mediated by increased top-down modulation of limbic brain regions including the amygdala and periaqueductal gray (Lanius et al., 2018; Nicholson et al., 2017).”
From Trauma-related dissociation and the autonomic nervous system: a systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients (2022) · cites this paper as Nicholson et al., 2017
Resting-state brain activation analyses tentatively support the idea of an overmodulated fear network through reports of altered functional connectivity between prefrontal and subcortical areas in dissociative PTSD patients.
“Although analyses on resting-state brain activation tentatively support the idea of an overmodulated fear network (see defense cascade and shutdown models) through reports of altered functional connectivity between prefrontal and subcortical areas in dissociative PTSD patients (Nicholson et al., 2017; Nicholson et al., 2019; Rabellino et al., 2018)”
From Trauma-related dissociation and the autonomic nervous system: a systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients (2022) · cites this paper as Nicholson et al., 2017
In patients with the PTSD dissociative subtype, the prefrontal cortex is thought to play an inhibitory role on subcortical structures identified in the innate alarm system, including the amygdala and the periaqueductal gray, which contributes to an emotion over-modulation symptom profile including depersonalization/derealization and emotional detachment behaviors.
“Moreover, in patients with the PTSD dissociative subtype, the prefrontal cortex is thought to play an inhibitory role on subcortical structures identified in the innate alarm system, including the amygdala and the periaqueductal gray, which contributes to an emotion over-modulation symptom profile, including depersonalization/derealization and emotional detachment behaviors (Lanius et al., 2010; N”
From How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD (2021) · cites this paper as Nicholson et al., 2017
Previous studies by our research group suggest that among individuals with the PTSD dissociative subtype, the prefrontal cortex exerts top-down inhibitory effects on emotional reactivity structures.
“Interestingly, these patterns differ from previous studies conducted by our research group that suggest among individuals with the PTSD dissociative subtype, the prefrontal cortex exerts top-down inhibitory effects on emotional reactivity structures (Lanius et al., 2010; Nicholson et al., 2017).”
From How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD (2021) · cites this paper as Nicholson et al., 2017
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References 50 · Cited by 159
Research works printed but not linked: 1
- First MB, Spitzer RL, Gibbon M, Williams JBW (2002): Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Patient Edition (SCID-I/P, 11/2002 revision) for DSMIV. New York, NY: Biometrics Research, New York State Psychiatric Institute.
- Authors
- Nicholson, A. A., Friston, K. J., Zeidman, P., Harricharan, S., McKinnon, M. C., Densmore, M., Neufeld, R. W. J., Théberge, J., Corrigan, F., Jetly, R., Spiegel, D., & Lanius, R. A.
- Affiliations
- Western University (CA)
- Wellcome Centre for Human Neuroimaging (GB)
- Homewood Research Institute (CA)
- Lawson Health Research Institute (CA)
- Argyll and Bute Hospital (GB)
- Department of National Defence (CA)
- Stanford Medicine (US)
- Corresponding author
- Lanius, Ruth A.
- ORCID
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2017-08-24
- Volume
- 38
- Issue
- 11
- Pages
- 5551-5561
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6866710
- OpenAlex
- W2746747038
- Cited by
- 159
- References
- 50
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 15 · 2023: 19 · 2022: 17 · 2021: 18 · 2020: 26 · 2019: 21 · 2018: 9 · 2017: 1 · 2012: 1
- FWCI
- 19.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- post-traumatic stress disorder, dissociative subtype of PTSD, dynamic causal modeling, effective connectivity, bottom-up processing, top-down control, ventromedial prefrontal cortex, amygdala, periaqueductal gray, fear processing, emotion regulation, hyperarousal, hypoarousal, resting-state functional connectivity
- MeSH terms
- Adult Survivors of Child Adverse Events, Adult, Bayes Theorem, Brain, Brain Mapping, Dissociative Disorders, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Stress Disorders, Post-Traumatic, Multivariate Analysis
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