Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets

PLoS One. 2015 Jul 1;10(7):e0129659. doi: 10.1371/journal.pone.0129659. eCollection 2015.


Background: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct.

Methods: Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large group of neuropsychiatric patients. Two groups were analyzed: Group 1 with TBI (n=104), PTSD (n=104) or both (n=73) closely matched for demographics and comorbidity, compared to each other and healthy controls (N=116); Group 2 with TBI (n=7,505), PTSD (n=1,077) or both (n=1,017) compared to n=11,147 without either. ROIs and visual readings (VRs) were analyzed using a binary logistic regression model with predicted probabilities inputted into a Receiver Operating Characteristic analysis to identify sensitivity, specificity, and accuracy. One-way ANOVA identified the most diagnostically significant regions of increased perfusion in PTSD compared to TBI. Analysis included a 10-fold cross validation of the protocol in the larger community sample (Group 2).

Results: For Group 1, baseline and on-task ROIs and VRs showed a high level of accuracy in differentiating PTSD, TBI and PTSD+TBI conditions. This carefully matched group separated with 100% sensitivity, specificity and accuracy for the ROI analysis and at 89% or above for VRs. Group 2 had lower sensitivity, specificity and accuracy, but still in a clinically relevant range. Compared to subjects with TBI, PTSD showed increases in the limbic regions, cingulum, basal ganglia, insula, thalamus, prefrontal cortex and temporal lobes.

Conclusions: This study demonstrates the ability to separate PTSD and TBI from healthy controls, from each other, and detect their co-occurrence, even in highly comorbid samples, using SPECT. This modality may offer a clinical option for aiding diagnosis and treatment of these conditions.

MeSH terms

  • Adult
  • Biomarkers
  • Brain Injuries / diagnosis*
  • Comorbidity
  • Databases, Factual
  • Diagnosis, Differential
  • Female
  • Functional Neuroimaging* / methods
  • Humans
  • Image Interpretation, Computer-Assisted
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Military Personnel
  • ROC Curve
  • Reproducibility of Results
  • Retrospective Studies
  • Severity of Illness Index
  • Stress Disorders, Post-Traumatic / diagnosis*
  • Tomography, Emission-Computed, Single-Photon / methods
  • Young Adult


  • Biomarkers

Grants and funding

The authors received no specific funding for this work. Author TH is President and owner of The Synaptic Space, Dr. Theodore Henderson, Inc. and co-owner of Neuro-Luminance Corp. The Synaptic Space, Dr. Theodore Henderson, Inc. and Neuro-Luminance Corp. did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the “author contributions” section. Author DA is the owner of Amen Clinics, Inc. Authors KW and DT are employed by Amen Clinics, Inc. Amen Clinics, Inc. provided support in the form of salaries for authors DA, KW and DT, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the “author contributions” section.