Up to 80% of the general population encounters severe adverse life events. For some, these events can lead to posttraumatic stress disorder (PTSD), a common disorder with a lifetime prevalence of about 7%1,2,3. Diagnostic criteria of PTSD are intrusions, avoidance of distressing trauma-related stimuli, hyperarousal, and negative alterations in cognitions, and mood (see DSM-54) and some patients show attention and memory deficits5,6. In particular, the symptom cluster of alterations in arousal and reactivity implies that PTSD patients typically respond to reminders of traumatic events - but also to neutral stimuli - with exaggerated startle response and hypervigilance4. High prevalence, difficulties in treatment7,8, and often debilitating consequences of the disorder illustrate the great need for investigating the underlying cognitive mechanisms of traumatic stress responses for PTSD. In the current study we investigated whether the brain’s response (measured using EEG) to a simple auditory sensory change was altered in patients with PTSD relative to trauma-exposed matched controls who did not develop the disorder.

The mismatch negativity (MMN) is an event-related potential (ERP) in response to deviant stimuli that differ from a sequence pattern of standard stimuli preceding it9. It represents the ability to automatically and without conscious effort compare among series of tones, to detect auditory changes, and to switch attention to potentially important events in the unattended auditory environment9,10,11. The MMN provides a neurophysiological index of auditory information processing, perceptual accuracy, learning, and memory; all related to automatic processing and largely not under direct control12,13. The MMN plays an important role in clinical research: Weaker MMN can predict psychosis onset14,15,16, perceptual and cognitive abnormalities in schizophrenia17,18,19, and impaired auditory frequency discrimination in dyslexia20. Increases in MMN amplitudes, by contrast, were found in adults with Asperger’s syndrome21,22, closed head injury23, alcoholism24,25, children with major depression26, and sleep disorders27. Stronger MMN responses for those patient groups may reflect enhanced discrimination of sound pattern22 and/or increased involuntary attention switching in response to auditory change13.

For PTSD, the MMN remains one of the least studied ERP components and results remain inconsistent (see Javanbakht28). Enhanced MMN has been previously found in high school students who have experienced an earthquake29 and in women with sexual assault-related PTSD30. Those effects may reflect enhanced involuntary attention to auditory deviations in PTSD as a result of chronic hyperarousal and hypervigilance. By contrast, some researchers found reduced MMN in PTSD, which has been interpreted as compensation for chronic hyperarousal31 or as difficulty to discriminate relevant from irrelevant stimuli due to overall neural hyperactivity32,33. So far, investigations on MMN in PTSD have been limited to specific target groups (high school students) or specific trauma etiologies (earthquake in China) and controls were not matched to the patients. One of our aims is therefore to study same-sex adults diagnosed with PTSD and trauma-exposed controls, matched by age, gender, and education, to investigate group differences in the MMN in response to auditory oddball stimuli.

Event-related potentials such as the MMN reflect change in the EEG over time and are phase locked to the onset of the stimuli. A shortcoming of the MMN as a clinical tool is that it cannot be reliably identified in every individual34. As such, another objective of the current study was to examine the induced changes in (i.e. responses in the EEG signal that are time-locked but not phase locked to events) elicited by the onset of deviant stimuli, as a new potential tool for characterizing and predicting PTSD; specifically, the suppression of oscillatory alpha band activity. The depth of stimulus processing in a relevant region is indicative by alpha suppression35,36 with the amount of alpha suppression reflecting the resources allocated to processing the stimulus37. Stimulus induced alpha modulation in healthy population can be reliably identified within individuals, and covaries with variability in attentional performance38,39.

Investigations into the alpha suppression effect have been applied to research into the neurobiological underpinnings of psychiatric disorders. For example, deviations in alpha suppression have been reported for schizophrenia40,41, bipolar disorder, depression42,43, and obsessive-compulsive disorder44,45. These studies suggest that induced oscillatory alpha activity—even in simple cognitive tasks—may be a valuable biomarker for psychiatry. Here, we will extend current findings and investigate induced oscillatory alpha in PTSD. Research in into oscillatory brain activity in PTSD has been limited to ongoing or resting oscillatory activity. For example, alpha-theta-ratio neurofeedback therapy has shown some degree of effectiveness for Vietnam veterans with combat-related PTSD46 and for patients with anxiety disorders, where alpha power changed in proportion to anxiety levels (for review see Moore47). Magnetic resonance therapy inducing alpha power increase resulted in decreases in PTSD symptom severity48. Finally, alpha asymmetry49, alpha peak frequency50, and power of right hemisphere frontal alpha correlated with PTSD symptom severity49,51 as well as executive task performance51.

Few studies have directly investigated alpha power changes in PTSD and results remain inconclusive49,52,53. Differences in oscillatory alpha activity during resting state were found among PTSD groups with different trauma etiology. Combat veterans with PTSD were compared to Chernobyl accident survivors with PTSD and showed decreased alpha and increased beta and theta power. However, when compared to controls without the disorder no effects for PTSD were found54. Begić et al. found increases in the upper alpha, but not in the lower alpha band, in PTSD55, while in a later study they found suppression of low alpha over frontal, central and occipital channels56. Increased alpha power was found during non-REM sleep for PTSD compared to trauma controls (Olff, personal communication, paper submitted). Besides those resting state EEG studies, a pilot MEG study on nine females with PTSD was conducted and showed reduced alpha power in left Broca area, insula and premotor cortex during tape-recorded auditory trauma imagery compared to neutral imagery57. Thus, most research into oscillatory power changes has focused on brain activity during trauma-exposure or at rest. There is strong evidence that hyper-responsivity in PTSD is not restricted to trauma-related stimuli or trauma-related thoughts during rest (see Casada et al.58 vs. Shin et al.59. PTSD patients show disadvantages in cognitive performance, e.g. tasks that involve attention and memory for neutral information60,61. If we detected neural hyperresponsiveness to neutral stimuli that are trauma-unrelated, we could contribute to a better understanding of deviations in automatic attention in PTSD patients. Anomalies in involuntary bottom-up attention in PTSD could explain attention-related problems on everyday tasks.

To investigate this, participants’ EEG was recorded while they were presented with neutral tones according to a simple auditory oddball task while watching a silent movie.

In the current study we investigated whether the brain’s evoked and induced responses to the occurrence of an oddball auditory stimuli were altered in PTSD patients relative to trauma-exposed matched controls. We predicted alterations of the MMN, increased theta band power and stronger suppression of alpha activity after deviant (vs. standard) tones in the PTSD group. We also examined if any of the brain responses correlated with PTSD symptom severity (assessed by the Clinician-Administered PTSD Scale for DSM-4; CAPS62) and cognitive task performance (assessed by CANTAB subtests).