A Ventromedial Prefrontal-to-Lateral Entorhinal Cortex Pathway Modulates the Gain of Behavioral Responding During Threat

Hisey, Erin; Purkey, Alicia; Gao, Yudong; Hossain, Kazi Amirul; Soderling, Scott H.; Ressler, Kerry J.

doi:10.1016/j.biopsych.2023.01.009

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…Similarly, we opted for a unitary approach to examine EC structure, despite its domain-sensitive subregions specialising in distinct episodic memory processes (Hunsaker et al, 2013 ; Reagh & Yassa, 2014 ; Schultz et al, 2012 ). Parsing the medial and lateral EC with high-resolution diffusion imaging represents an important future direction which, given their relevance to posterior-medial and anterior-temporal cortical networks, may provide further insights into the neurobiological implications of greater circulating PACAP in arousal-mediated memory circuits (Hisey et al, 2023 ; Ritchey et al, 2015 ). Despite the potential for increased granularity of NODDI measures in these regions to yield deeper information, to our knowledge, we are the first to apply this method to studies of MTL gray matter in PTSD.…”

Section: Discussionmentioning

confidence: 99%

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

Granger,

May,

Hammack

et al. 2024

European Journal of Psychotraumatology

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Introduction: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been investigated in PTSD. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analyses), and EC (secondary) using Neurite Orientation Dispersion and Density Imaging. Methods: Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure. Results: Higher PACAP levels were associated with greater EC NDI ( β = 0.0099, q = 0.032) and lower EC ODI ( β = −0.0073, q = 0.047), and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures. Conclusions: Circulating PACAP levels were associated with altered neuronal density of the EC but not the hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits in PTSD.

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Section: Discussionmentioning

confidence: 99%

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

Granger,

May,

Hammack

et al. 2024

European Journal of Psychotraumatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…We also chose a unitary structure for the EC despite its domainsensitive subregions specializing in different episodic memory processes (65)(66)(67). Parsing the medial and lateral EC with high-resolution diffusion imaging would be an important future direction, given their relevance to posterior-medial and anterior-temporal cortical networks, which may provide further insight into the neurobiological impact of greater circulating PACAP in arousal-mediated memory circuits (68,69). Despite the potential that increased granularity NODDI measures within these regions may yield improved information, to our knowledge, we are the first to apply this method to studies of MTL gray matter in PTSD.…”

Section: Discussionmentioning

confidence: 99%

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

Granger,

May,

Hammack

et al. 2023

Preprint

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Background. Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been reported. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analysis), and EC (secondary analysis) using Neurite Orientation Dispersion and Density Imaging. Methods. Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure. Results. Higher PACAP levels in blood were associated with greater EC NDI (β=0.31, q=0.034) and lower EC ODI (β=-0.30, q=0.042) and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures. Conclusions. Circulating PACAP levels were associated with altered neuronal density of the EC but not hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits.

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Activation of trace amine-associated receptor 1 ameliorates PTSD-like symptoms

Peng,

Zhang,

Feng

et al. 2024

Biochemical Pharmacology

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A Ventromedial Prefrontal-to-Lateral Entorhinal Cortex Pathway Modulates the Gain of Behavioral Responding During Threat

Cited by 5 publications

References 35 publications

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

Activation of trace amine-associated receptor 1 ameliorates PTSD-like symptoms

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