Spontaneous brain activity in combat related PTSD

Highlights

• PTSD shows increased spontaneous activity at amygdala and insula.

• PTSD shows decreased spontaneous activity at precuneus and thalamus.

• Precuneal and thalamic activity negatively correlates with re-experiencing symptoms.

Abstract

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder, especially in combat veterans. Existing functional neuroimaging studies have provided important insights into the neural mechanisms of PTSD using various experimental paradigms involving trauma recollection or other forms of emotion provocation. However it is not clear whether the abnormal brain activity is specific to the mental processes related to the experimental tasks or reflects general patterns across different brain states. Thus, studying intrinsic spontaneous brain activity without the influence of external tasks may provide valuable alternative perspectives to further understand the neural characteristics of PTSD. The present study evaluated the magnitudes of spontaneous brain activity of male US veterans with or without PTSD, with the two groups matched on age, gender, and ethnicity. Amplitudes of low frequency fluctuation (ALFF), a data driven analysis method, were calculated on each voxel of the resting state fMRI data to measure the magnitudes of spontaneous brain activity. Results revealed that PTSD subjects showed increased spontaneous activity in the amygdala, ventral anterior cingulate cortex, insula, and orbital frontal cortex, as well as decreased spontaneous activity in the precuneus, dorsal lateral prefrontal cortex and thalamus. Within the PTSD group, larger magnitudes of spontaneous activity in the thalamus, precuneus and dorsal lateral prefrontal cortex were associated with lower re-experiencing symptoms. Comparing our results with previous functional neuroimaging findings, increased activity of the amygdala and anterior insula and decreased activity of the thalamus are consistent patterns across emotion provocation states and the resting state.

Introduction

Posttraumatic stress disorder (PTSD) is an anxiety disorder that may emerge following a traumatic event. It is characterized by a group of symptoms including re-experiencing of traumatic memories, hyperarousal, avoidance and emotional numbing [49]. PTSD is particularly prevalent among combat veterans [5], for example, approximately 18% of the army had PTSD after deployment to Iraq, which is much higher than the pre-deployment rate of 9.4% [20]. Functional neuroimaging studies, with positron emission tomography or blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), have identified several brain structures associated with PTSD [27], such as the amygdala, medial prefrontal cortex, insula [39], [40], thalamus, and the anterior cingulate cortex [32]. These studies have used various experimental tasks involving trauma recollection or other forms of emotional processes; however, it is not clear whether the observed abnormal neural responses are specific to the mental processes targeted by the experimental tasks or reflect general functionality across different brain states. Therefore, studying the intrinsic spontaneous brain activity using resting state fMRI, which is conducted without prescribed external tasks, may provide valuable alternative insights into the pathogenesis of PTSD.

Although the neural activity in “resting state” is still a burgeoning area of research, it has been postulated that “rest activity patterns may reflect neural functions that consolidate the past, stabilize brain ensembles, and prepare us for the future” [9]. A large number of studies have confirmed that resting state fMRI is an informative and reliable research approach [37], which can provide valuable insights for understanding neurological and psychiatric disorders [8], including PTSD [7], [26], [42]. Existing resting state fMRI studies of PTSD are focused on functional connectivity [7], [26], [42], which reflects the temporal synchronization in pre-defined brain circuitries, rather than magnitudes of spontaneous brain activity. In order to evaluate the spontaneous brain activity in resting state to compare with the patterns of brain activity in task-based neuroimaging studies, the present study used an established protocol to calculate the amplitudes of low frequency fluctuation (ALFF) on each voxel [51], followed by voxelwise group statistics to identify brain areas with significantly higher or lower magnitudes of spontaneous activity. This protocol was previously used in two PTSD cohorts studied soon after exposure to single incident traumatic events [4], [50], but it is not clear whether the findings also apply to other types of trauma. The present study focuses on combat veterans, who have experienced prolonged repeated trauma during their deployment to Iraq and Afghanistan. Considering the heterogeneity of PTSD neuroimaging findings with respect to types of trauma [22], [27], the present study may reveal different patterns compared to previous studies. It is also worth noting that the present study has a much larger sample compared to the majority of the above mentioned studies [4], [7], [26], [42].

Based on existing findings from functional neuroimaging studies of PTSD, we were interested to see the patterns of spontaneous activity in the amygdala, insula, anterior cingulate cortex and the thalamus. Among these, increased activation at the amygdala and insula and decreased activation in the thalamus seem to be relatively consistent findings in previous studies, thus we predicted that in resting state, PTSD compared controls would also demonstrate increased spontaneous activity in the amygdala and insula and decreased thalamic spontaneous activity. The data-driven whole brain voxelwise analysis approach also allowed us to identify other brain regions demonstrating significant group differences.