Spontaneous brain activity in combat related PTSD
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.
Section snippets
Participants
Participants were recruited from New York City Veteran Affairs medical centers at Manhattan and Bronx, as well as other veteran service organizations. Participants gave written informed consent after receiving a complete description of the study. All procedures were approved by the Institute Review Boards of NYU School of Medicine and Mount Sinai School of Medicine. General inclusion criteria include being a US veteran who served in Operation Enduring Freedom in Afghanistan and/or Operation
Results
The two groups were matched on age, gender, and ethnicity. The PTSD group had a mean age of 33.18 (standard deviation, SD = 7.60, range 23–52) and the control group had a mean age of 33.57 (SD = 8.98, range 20–57). The average CAPS score for the PTSD group was 66.75 with a standard error (SE) of 2.69, which was significantly higher (p < 0.001) than that of the control group (mean ± SE = 4 ± 0.93). In the PTSD group, the average scores of BDI, PCL-M, and the re-experiencing, avoidance and hyperarousal
Discussion
The present study examined magnitudes of spontaneous brain activity in US veterans who served in Iraq and Afghanistan. Compared to warzone exposed controls, veterans with PTSD showed increased spontaneous activity in the left amygdala, right anterior insula, ventral anterior cingulate cortex, and orbital frontal cortex, and decreased spontaneous activity in the precuneus, dorsal lateral prefrontal cortex, and thalamus. The following discussion will compare the spontaneous brain activity in the
Acknowledgment
This work has been supported by the U.S. Department of Defense (#W81XWH-09-2-0044).
References (51)
- et al.
Default-mode brain dysfunction in mental disorders: a systematic review
Neurosci. Biobehav. Rev.
(2009) - et al.
Unrest at rest: default activity and spontaneous network correlations
Neuroimage
(2007) - et al.
Brain activation to phobia-related pictures in spider phobic humans: an event-related functional magnetic resonance imaging study
Neurosci. Lett.
(2003) - et al.
The mind's eye – precuneus activation in memory-related imagery
Neuroimage
(1995) - et al.
The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis
Neuroimage
(2008) - et al.
Precuneal activity during encoding in veterans with posttraumatic stress disorder
Prog. Brain Res.
(2007) - et al.
A meta-analysis of structural brain abnormalities in PTSD
Neurosci. Biobehav. Rev.
(2006) - et al.
Decreased cerebral blood flow of thalamus in PTSD patients as a strategy to reduce re-experience symptoms
Acta Psychiatr. Scand.
(2007) - et al.
Twin studies of posttraumatic stress disorder: differentiating vulnerability factors from sequelae
Neuropharmacology
(2012) - et al.
A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation
J. Psychiatr. Res.
(2006)
Neural correlates of trauma script-imagery in posttraumatic stress disorder with and without comorbid major depression: a functional MRI investigation
Psychiatry Res.: Neuroimaging
Recall of emotional states in posttraumatic stress disorder: an fMRI investigation
Biol. Psychiatry
Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder
Trends Neurosci.
Characterizing the hemodynamic response: effects of presentation rate, sampling procedure, and the possibility of ordering brain activity based on relative timing
Neuroimage
An fMRI study of anterior cingulate function in posttraumatic stress disorder
Biol. Psychiatry
Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-I/P)
Psychiatry Res.
Trauma modulates amygdala and medial prefrontal responses to consciously attended fear
Neuroimage
Abnormal baseline brain activity in posttraumatic stress disorder: a resting-state functional magnetic resonance imaging study
Neurosci. Lett.
Neural systems underlying the suppression of unwanted memories
Science
An inventory for measuring depression
Arch. Gen. Psychiatry
Dissociative flashbacks after right frontal injury in a Vietnam veteran with combat-related posttraumatic stress disorder
J. Neuropsychiatry Clin. Neurosci.
Alterations in the cortical thickness and the amplitude of low-frequency fluctuation in patients with post-traumatic stress disorder
Brain Res.
Prevalence of PTSD symptoms in combat veterans seeking medical treatment
J. Trauma. Stress
The development of a clinician-administered PTSD scale
J. Trauma. Stress
Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma
J. Psychiatry Neurosci.
Cited by (72)
Neural correlates of PTSD in women with childhood sexual abuse with and without PTSD and response to paroxetine treatment: A placebo-controlled, double-blind trial
2023, Journal of Affective Disorders ReportsStructural changes in the thalamus and its subregions in regulating different symptoms of posttraumatic stress disorder
2023, Psychiatry Research - NeuroimagingTranscriptional signal and cell specificity of genes related to cortical structural differences of post-traumatic stress disorder
2023, Journal of Psychiatric ResearchExpanding the canon: An inclusive neurobiology of thalamic and subthalamic fear circuits
2023, NeuropharmacologyFunctional and structural brain abnormalities in posttraumatic stress disorder: A multimodal meta-analysis of neuroimaging studies
2022, Journal of Psychiatric Research