Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

Abstract

Post-traumatic stress disorder (PTSD) is a prevalent, debilitating and sometimes deadly consequence of exposure to severe psychological trauma. Although effective treatments exist for some individuals, they are limited. New approaches to intervention, treatment and prevention are therefore much needed. In the past few years, the field has rapidly developed a greater understanding of the dysfunctional brain circuits underlying PTSD, a shift in understanding that has been made possible by technological revolutions that have allowed the observation and perturbation of the macrocircuits and microcircuits thought to underlie PTSD-related symptoms. These advances have allowed us to gain a more translational knowledge of PTSD, have provided further insights into the mechanisms of risk and resilience and offer promising avenues for therapeutic discovery.

Environmental variables that ameliorate extinction learning deficits in the 129S1/SvlmJ mouse strain

“…These results are in support of previous studies showing that the 129S1 have reduced levels of locomotion and increased basal maladaptive fear behavior. 1 ORCID Victor A. Cazares https://orcid.org/0000-0002-6625-7103 Our studies are unable to fully distinguish whether increased immobility in the 129S1 is due to, or influenced by, innate fear to the experimental contexts or is a phenotype that is independent of fear or anxiety.…”

“…1,2 Rodent models of fear learning (ie, fear conditioning) and fear extinction learning have enriched our understanding of genes and neural circuits involved in the expression of GAD and PTSD symptoms (reviewed in Fenster et al 1 ). In humans, maladaptive fear or deficits in extinction learning are core features of generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD).…”

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting‐state functional connectivity and its predictive validity using machine learning

“…Notably, visual cortex activation has been observed consistently in studies involving individuals with the dissociative subtype of PTSD (see Daniels et al, 2012Daniels et al, , 2016Lanius et al, 2002Lanius et al, , 2005 and forms part of an occipital resting-state network that facilitates visual mental imagery (K. Wang et al, 2008). Here, whereas implicit memory responses to visual priming cues appear intact among individuals that experience dissociation, explicit memory processes are relatively impaired (Devilly et al, 2007;Eich, Macaulay, Loewenstein, & Dihle, 1997;Elzinga, Phaf, Ardon, & Van Dyck, 2003;Fenster et al, 2018;Kihlstrom, 2005). Taken together, these results point toward the need for additional research to clarify the role of implicit memory in the processing of salient environmental stimuli among individuals with PTSD+DS.…”

“…Post‐traumatic stress disorder (PTSD) is characterized by emotion dysregulation, including prominently states of reliving and of hypervigilance, which are thought to be mediated in part by decreased prefrontal inhibition on limbic (e.g., amygdala) and brainstem (e.g., periaqueductal gray) regions (Corrigan, Fisher, & Nutt, ; Fenster, Lebois, Ressler, & Suh, ; Lanius et al, ; Litz, ; Nicholson et al, ; Shalev, Liberzon, & Marmar, ; Yehuda et al, ). By contrast, the dissociative subtype of PTSD (PTSD+DS) is associated with symptoms of depersonalization, derealization and concomitant emotional detachment (Daniels, Frewen, Theberge, & Lanius, ; Lanius et al, ; Melara, Ruglass, Fertuck, & Hien, ; Sierra & Berrios, ), which are thought to be mediated by increased top‐down prefrontal inhibition on limbic and brainstem regions (Nicholson et al, ).…”

ENCODS: A novel initiative to inspire young neuroscientists

“…Over the past decade, the exploration of brain circuits through different imaging methods has become an important and illuminating field of research in the neurosciences (Pastrana, ). This approach provides insight for the understanding of phenomena such as the establishment of motor pathways (Economo et al., ), social behaviours (Benekareddy et al., ) and pathologies such as post‐traumatic stress disorder (Fenster, Lebois, Ressler, & Suh, ), Parkinson's disease (Ridler, ) and Alzheimer's disease (Busche & Konnerth, ).…”