Circuit dysregulation and circuit-based treatments in posttraumatic stress disorder

Abstract

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that develops in some individuals in the aftermath of exposure to traumatic events, such as actual or threatened death, serious injury or sexual assault. It has been hypothesized that dysregulations in a number of specific neurocircuits, characterized by heightened responsivity of amygdala, dACC and insula, diminished responsivity of mPFC, impaired hippocampal function and deficits in cortical regions, underlie the development and expression of key PTSD symptoms. Here, we concisely describe three functional neural circuits implicated in PTSD pathophysiology and briefly review selected treatment strategies in the context of these neural circuits. We start with the commonly implicated neurocircuit model, namely, the fear learning and threat detection circuits, and then discuss the context processing circuitry, which plays an important role among others, in fear regulation. We then discuss the emotion regulation circuitry, which can further contribute to PTSD pathophysiology, and conclude with a discussion of the therapeutic approaches that might be targeting dysregulation in these circuits in PTSD patients. Specifically, we discuss how exposure-based treatments might be targeting fear learning circuits, and the pharmacological and brain-stimulation interventions aimed to augment these therapies. Finally, we discuss other pharmacological and cognitive therapeutic approaches that can augment or restore the function of the context processing and emotional regulation circuits.

One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder

“…The default mode, salience, and executive control networks and their functional neurocircuitry have been shown to be implicated in the pathology of PTSD [e.g., refs. [29][30][31]. Six millimeter seed spheres were constructed for 20 seeds in the default mode, executive control, and salience networks using the MarsBaR Toolbox (http://marsbar.sourceforge.net/).…”

Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder

“…The amygdala is particularly relevant for both the recognition (often at a preconscious level) of threatening stimuli in the environment, as well as the assembly of a behavioral response to threat, such as the generation of states of vigilance (Duvarci and Pare, 2014;Janak et al, 2015;LeDoux, 2007). With respect to PTSD, the amygdala appears to be hyper-reactive, exhibiting elevated metabolic activity during periods of heightened symptom presentation and showing increased responsiveness to emotionally salient information, even stimuli unrelated to the trauma itself (Diamond and Zoladz, 2016;Hughes and Shin, 2011;Sheynin and Liberzon, 2016;Shin et al, 2006).…”

Memory and Forgetting

“…The amygdala is regulated by top-down control from the medial prefrontal cortex, with the dorsal anterior cingulate cortex being involved in the expression of fear and the ventromedial region of the prefrontal cortex being involved in the recall of fear extinction. Another circuit, involving the amygdala, medial prefrontal cortex, and hippocampus, is concerned with the processing of context, enabling what has been learned about threat to be expressed or inhibited depending on the prevailing conditions [ 34 ].…”