Threat-Induced Anxiety During Goal Pursuit Disrupts Amygdala-Prefrontal Cortex Connectivity in Posttraumatic Stress Disorder

Abstract

To investigate how unpredictable threat during goal pursuit impacts fronto-limbic activity and functional connectivity in posttraumatic stress disorder (PTSD), we compared military veterans with PTSD (n=25) versus trauma-exposed Control (n=25). Participants underwent functional magnetic resonance imaging (fMRI) while engaged in a computerized chase-and-capture game task that involved optimizing monetary rewards obtained from capturing virtual prey while simultaneously avoiding capture by virtual predators. The game was played under two alternating contexts – one involving exposure to unpredictable, task-irrelevant threat by randomly occurring electrical shocks, and a nonthreat control condition. Activation in and functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) was tested across threat and nonthreat task contexts with generalized psychophysiological interaction (gPPI) analyses. PTSD patients reported higher anxiety than controls across contexts. Better task performance represented by successfully avoiding capture by predators under threat than nonthreat contexts was associated with stronger left amygdala-vmPFC functional connectivity in controls and greater vmPFC activation in PTSD patients. PTSD symptom severity was negatively correlated with vmPFC activation in trauma-exposed controls and with right amygdala-vmPFC functional connectivity across all participants in the threat relative to nonthreat contexts. The findings showed that veterans with PTSD have disrupted amygdala-vmPFC functional connectivity and greater localized vmPFC processing under threat-modulation of goal-directed behavior, specifically related to successful task performance while avoiding loss of monetary rewards. In contrast, trauma survivors without PTSD rely on stronger threat-modulated left amygdala-vmPFC functional connectivity during goal-directed behavior, which may represent a resilience-related functional adaptation.

Decoding shared versus divergent transcriptomic signatures across cortico-amygdala circuitry in PTSD and depressive disorders

“…Disruption of neural activity in these cortico-amygdala circuits is thought to reflect altered functional connectivity between the two regions, influencing behaviors that are frequently disrupted in PTSD including fear processing, anxiety and stress coping 13–16 . In accordance with human neuroimaging studies that show altered signaling in cortico-amygdala circuits in PTSD 13,16-18 , studies in animal models of behavior demonstrate that function in these circuits is strongly impacted by exposure to stress and trauma. Moreover, experimentally manipulating neuronal activity in cortico-amygdala circuits or altering key cell signaling pathways in these brain regions is associated with changes in fear processing and anxiety 19–22 .…”

Common default mode network dysfunction across psychopathologies: A neuroimaging meta-analysis of the n-back working memory paradigm

“…Literature linking aberrant mPFC function to psychiatric disorders is replete. For example, structural analyses suggest that mPFC-amygdala white matter connectivity predicts anxiety and depressive symptoms in childhood (35), and functional connectivity between these regions is negatively correlated with PTSD symptoms (36). Smaller mPFC volume in adolescents predicts ADHD symptoms after 5 years, while mPFC activity in individuals with schizophrenia and comorbid nicotine addiction (relative to healthy controls) is enhanced following exposure to cigarette cues (37).…”

Kognitive Neurowissenschaft der psychischen Resilienz

“…Die kortikolimbische Regulation kehrt nicht nur psychopatho logische Zustände um, sondern zeigt sich auch bei gesunden Per sonen als neuronales Korrelat der Emotionsregulation [54]. Wei ter gibt es inzwischen eine Reihe neurokognitiver Resilienzstudien, die auf eine ausgeglichene kortikolimbische Regulation als Resi lienzmechanismus hinweisen [34,[55][56][57][58][59][60]. Diese Studien sind vor allem querschnittlich und kategorial, d. h. es wurden Gruppen un tersucht, die Stressoren erlebt hatten und dann diejenigen mit und ohne Traumafolgestörung verglichen.…”

“…Der vmPFC zeigte zudem eine erhöhte inhibitori sche Konnektivität zur Amygdala bei Personen, die einen Taifun resilient überstanden hatten im Vergleich zu solchen, die danach eine posttraumatische Belastungsstörung (PTBS) entwickelt hat ten [57]. Wir konnten in eigenen Untersuchungen eine erhöhte Konnektivität zur Amygdala bei Personen zeigen, die trotz famili ären Depressionsrisikos keine Depression entwickelt hatten [ [34,59,60]. Eine fMRTStudie zum Sicherheitslernen zeigte zudem eine erhöhte Reaktivität von Amygdala und dlPFC bei gesunden Jugendlichen mit familiärem Ri siko für Angststörungen als möglichen Resilienzmarker, während Jugendliche mit Angststörung keine differenziellen Effekte im lim bischpräfrontalen Netzwerk durch Sicherheitslernen zeigten [61].…”