Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

Abstract

IntroductionPosttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder characterized by symptoms of re-experiencing, hyperarousal, emotional numbing and avoidance; 1 however, exact brain mechanisms involved in the generation of PTSD symptoms or in PTSD pathophysiology have yet to be elucidated. Converging neuroimaging research points to a potentially critical role for disrupted emotion neurocircuitry in individuals with PTSD, and whereas many studies have delineated patterns of activations during face viewing or symptom provocation (for a review, see Shin and Liberzon 2 ), relatively few have examined patterns of connectivity in the brains of patients with PTSD at rest, a potentially powerful method for illuminating brain network structure. 3,4 Most PTSD neuroimaging studies to date have described abnormalities in emotion-generation regions, such as the amygdala or insula, and emotion-regulation regions, including the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC). This is consistent with the known role of the amygdala as a key region in threat detection, 5 fear conditioning 6 and emotional salience, 7 and of the mPFC as a modulatory region interconnected with limbic structures 8 and involved in emotion regulation.9 Taken together, functional magnetic resonance imaging (fMRI) studies of individuals with PTSD suggest patterns of hyperactivation of the amygdala and insula to emotion-related stimuli and corresponding hypoactivation of ventromedial prefrontal and rostral anterior cingulate cortices.2 This pattern of amygdala hyperactivity and mPFC hypoactivity was recently confirmed by a meta-analysis of 15 PTSD neuroimaging studies 10 and is generally understood to reflect a lack of regulatory control over emotion in individuals with PTSD.Studies of functional connectivity, however, can provide additional and potentially more direct information about regu latory relationships between the mPFC and amygdala. The amygdala has tight structural connections and reciprocal feedback loops with the mPFC and orbitofrontal cortex 11 as well as with the dorsolateral PFC 12 and ACC. 13 As amygdala Background: Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. Methods: Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. Results: Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with ...

Hippocampal Network Connectivity and Activation Differentiates Post-Traumatic Stress Disorder From Generalized Anxiety Disorder

“…Moreover, studies of both PTSD and GAD have implicated abnormalities in amygdala connectivity (Etkin et al, 2009;Rabinak et al, 2011;Sripada et al, 2012a), which may be more closely related to the anterior hippocampus. Direct functional neuroimaging comparisons of PTSD with any other psychiatric disorder, however, are still extremely rare (Etkin and Wager, 2007).…”

Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

“…The prevailing neurocircuitry model of PTSD postulates amygdala hyperactivity and ventromedial prefrontal cortex (vmPFC) hypoactivity toward both trauma-related and non-trauma-related stimuli (Pitman et al, 2012). According to a meta-analysis of functional connectivity studies in PTSD, amygdala hyperactivity in PTSD patients was predominantly observed in response to negative, non-trauma-related stimuli (Hayes et al, 2012;Sripada et al, 2012). This may result in decreased prefrontal control over the fear response and hence excessive fear in PTSD patients (Rauch et al, 2006).…”

Traumatic Experiences Disrupt Amygdala – Prefrontal Connectivity

“…The results of this study suggest that the resting-state connectivity of the posterior cingulate cortex/precuneus with the perigenual ACC and right amygdala is associated with current PTSD symptoms and that the correlation with the right amygdala predicts future PTSD symptoms (Lanius et al, 2010). Another study measuring resting-state amygdala connectivity in male veterans with PTSD (n=15) and in combat controls (n=14) showed greater positive connectivity between the amygdala and the insula in patients with PTSD than in controls, reduced positive connectivity between the amygdala and the hippocampus, and a reduced anticorrelation between the amygdala and the dorsal and rostral ACC (Sripada et al, 2012).…”