36 - Cognitive flexibility in post-traumatic stress disorder: slowed performance associated with altered modulation of cortical oscillatory activity during task-switching

Abstract Text:

Introduction: The ability to adapt behavior by shifting attention and inhibiting pre-existing action plans, referred to as cognitive flexibility, is an important aspect of executive control. Recent studies observed that deficits in cognitive flexibility in the aftermath of a psychologically traumatic event are predictive of the subsequent development of post-traumatic stress disorder (PTSD), with the severity of the cognitive flexibility impairment correlating with the severity of PTSD symptoms. Furthermore, these studies showed that successful remediation of cognitive flexibility deficits with cognitive flexibility training can reduce the incidence of subsequent PTSD. Current theories posit the existence of bidirectional reinforcement between core symptoms of post-traumatic stress disorder (PTSD) and deficits in cognitive flexibility, but the physiological mechanisms underlying this association are not well understood. In this study, we investigated the relationship between severity of PTSD symptoms, behavioral measures of cognitive flexibility, and modulation of oscillatory brain activity in service members with combat exposure.

Methods: Study participants (n=91) were service members enrolled in an outpatient program for patients with a history of traumatic brain injury and associated post-concussive and psychological health symptoms at the National Intrepid Center of Excellence (NICoE), Walter Reed National Military Medical Center. Participants were assigned to three groups based on symptom severity assessed with the PTSD Check List for DSM-V (PCL-5): Group 1 included participants with low PTSD symptom severity (n=30, PCL-5 score ≤ 15), Group 2 included participants with moderate PCL-5 scores (n=32, 16 ≤ PCL-5 score ≤ 33), and Group 3 included participants with high PTSD symptom severity (n=29, PCL-5 score ≥ 35). The inclusion of participants with low PTSD symptom severity (which would not be consistent with a diagnosis of PTSD) in our study serves to control for trauma exposure. No significant group differences were present for age, education, and combat exposure. Magnetoencephalography (MEG) data were recorded while participants performed a cued rule-switching task that required them to indicate if simultaneously presented visual stimuli match with respect to either shape or color. Each trial started with a cue that indicated what rule needs to be used in the current trial. The cue was displayed for 750 ms and was replaced by the test stimuli. The matching rule was repeated or switched across consecutive trials. MEG data were processed using independent component analysis to remove cardiac and eye movement interferences prior to filtering the data in theta (4-7 Hz), alpha (7.5-13 Hz), beta (14-30 Hz) and gamma (35-100 Hz) frequency bands. The cortical current distribution was estimated using a minimum-norm algorithm. The signal power was integrated in 84 cortical regions and averaged across trials. For each frequency band and brain region, the change in power over temporal intervals following the start of each trial with respect to a baseline interval preceding the trial onset was compared between groups.

Results: Participants with high PTSD symptom severity had longer reaction times and no significant switch cost (or repetition benefit) defined as the difference in reaction times for switch versus repeat trials. During the cue-stimulus interval, participants with moderate and high PTSD symptom severity showed an increase in relative theta power in switch trials over left caudal middle frontal cortex and superior frontal gyrus. After stimulus onset, participants with high PTSD symptom severity showed reduced suppression of beta band activity. This was observed over multiple prefrontal, parietal, and temporal cortical regions in switch trials, and it was confined to bilateral rostral anterior cingulate and medial orbitofrontal cortex in repeat trials.

Conclusions: The high theta band activity observed in patients with moderate and severe PTSD symptoms is a marker of effortful pro-active re-orienting of attention to alternative stimulus features and stimulus-response contingencies. Reduced suppression of beta band activity during reactive processes may reflect difficulties with inhibition of neuronal representations for competitive perceptual information and alternative courses of action in PTSD. In particular, such difficulties with the inhibition of neuronal representations in ventromedial prefrontal regions that interface sensory systems to action selection (rostral anterior cingulate and medial orbitofrontal cortex) may undermine the ability to inhibit emotional reactions (regulate emotions), a symptom known to be associated with PTSD.

Keywords: Post traumatic stress, PTSD, Magnetoencephalography, MEG, Cognitive, TBI, neural modulation,