Randomized trial of rTMS in traumatic brain injury: improved subjective neurobehavioral symptoms and increases in EEG delta activity.

PRIMARY OBJECTIVE: While repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for cognitive difficulties accompanying depression, it is unknown if it can improve cognition in persons with traumatic brain injury. RESEARCH DESIGN: Using a sham-controlled crossover design, we tested the capacity of high frequency rTMS of the prefrontal cortex to improve neuropsychological performance in attention, learning and memory, and executive function. METHODS: Twenty-six participants with cognitive complaints and a history of mild-to-moderate traumatic brain injury were randomly assigned to receive first either active or sham 10 Hz stimulation for 20 minutes (1200 pulses) per session for five consecutive days. After a one-week washout, the other condition (active or sham) was applied. Pre- and post-treatment measures included neuropsychological tests, cognitive and emotional symptoms, and EEG. MAIN OUTCOMES AND RESULTS: Results indicated no effect of treatment on cognitive function. Subjective measures of depression, sleep dysfunction, post-concussive symptoms (PCS), and executive function showed significant improvement with stimulation, retaining improved levels at two-week follow-up. EEG delta power exhibited elevation one week after stimulation cessation. CONCLUSIONS: While there is no indication that rTMS is beneficial for neuropsychological performance, it may improve PCS and subjective cognitive dysfunction. Long-term alterations in cortical oscillations may underlie the therapeutic effects of rTMS.

Rapid-Response Impulsivity Predicts Depression and Posttraumatic Stress Disorder Symptomatology at 1-Year Follow-Up in Blast-Exposed Service Members.

OBJECTIVE: To determine if elevated rapid-response impulsivity after blast exposure (as a putative marker of ventral prefrontal cortex [vPFC] damage) is predictive of future elevated affective symptomatology in blast-exposed service members. DESIGN: Longitudinal design with neurocognitive testing at initial assessment and 1-year follow-up assessment of psychiatric symptomatology by telephone interview. SETTING: Veterans Administration medical centers and postdeployment assessment centers at military bases. PARTICIPANTS: Blast-exposed U.S. military personnel (N=84) ages 19 to 39 years old. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Center for Epidemiological Studies-Depression Scale (CES-D) scores, Posttraumatic Stress Disorder Checklist Version 5 (PCL-5) scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the 12-month follow-up telephone interview. RESULTS: After controlling for age and affective symptom scores reported at the initial assessment, commission errors on the Continuous Performance Test-II of the initial assessment were predictive of higher symptom scores on the CES-D and PCL-5 at follow-up, but were not predictive of AUDIT-C scores. CONCLUSIONS: Elevated rapid-response impulsivity, as a behavioral marker of reduced top-down frontocortical control, is a risk factor for elevated mood and posttraumatic stress disorder symptoms over time in blast-exposed individuals. Future longitudinal studies with predeployment neurobehavioral testing could enable attribution of this relation to blast-related vPFC damage.

Symptom Trajectories After Military Blast Exposure and the Influence of Mild Traumatic Brain Injury.

BACKGROUND: Blast-related mild traumatic brain injury (blast mTBI) is a signature wound of recent US military conflicts in the Middle East, but the relatedness of postconcussive symptoms (PCS) to the blast mTBI is unclear, and longitudinal symptom data are sparse. OBJECTIVES: To characterize postdeployment symptom levels and trajectories and to determine relationship to blast mTBI. METHODS: A total of 216 participants within 2 years of blast exposure during deployment underwent structured interviews or algorithmic questionnaires for blast mTBI. Detailed symptom inventories for PCS, pain, posttraumatic stress disorder, and depression were taken serially at enrollment, 6 months, and 12 months later. Repeated-measure analysis of variance models were built. RESULTS: Up to 50% of participants had at least 1 high-grade blast mTBI (with posttraumatic amnesia), 31% had low-grade only, and 19% had neither. Within the entire cohort, all 4 composite symptom scores started high and stayed unchanged. Between blast mTBI groups, symptom scores differed at every time point with some evidence of convergence over time. The PCS groups, different by definition to start, diverged further over time with those initially more symptomatic becoming relatively more so. CONCLUSIONS: History of blast mTBI accompanied by posttraumatic amnesia is associated with greater nonspecific symptoms after deployment, and prognosis for improvement when symptoms are prominent is poor.

Factor analysis of persistent postconcussive symptoms within a military sample with blast exposure.

OBJECTIVE: To determine the factor structure of persistent postconcussive syndrome symptoms in a blast-exposed military sample and validate factors against objective and symptom measures. SETTING: Veterans Affairs medical center and military bases. PARTICIPANTS: One hundred eighty-one service members and veterans with at least 1 significant exposure to blast during deployment within the 2 years prior to study enrollment. DESIGN: Confirmatory and exploratory factor analyses of the Rivermead Postconcussion Questionnaire. MAIN MEASURES: Rivermead Postconcussion Questionnaire, PTSD (posttraumatic stress disorder) Symptom Checklist-Civilian, Center for Epidemiological Studies Depression scale, Sensory Organization Test, Paced Auditory Serial Addition Test, California Verbal Learning Test, and Delis-Kaplan Executive Function System subtests. RESULTS: The 3-factor structure of persistent postconcussive syndrome was not confirmed. A 4-factor structure was extracted, and factors were interpreted as reflecting emotional, cognitive, visual, and vestibular functions. All factors were associated with scores on psychological symptom inventories; visual and vestibular factors were also associated with balance performance. There was no significant association between the cognitive factor and neuropsychological performance or between a history of mild traumatic brain injury and factor scores. CONCLUSION: Persistent postconcussive symptoms observed months after blast exposure seem to be related to 4 distinct forms of distress, but not to mild traumatic brain injury per se, with vestibular and visual factors possibly related to injury of sensory organs by blast.

Insomnia symptoms and behavioural health symptoms in veterans 1 year after traumatic brain injury.

OBJECTIVE: Insomnia and behavioural health symptoms 1 year after traumatic brain injury (TBI) were examined in a clinical sample representative of veterans who received inpatient treatment for TBI-related issues within the Veterans Health Administration. METHODS: This was a cross-sectional sub-study (n = 112) of the Polytrauma Rehabilitation Centres' traumatic brain injury model system programme. Prevalence estimates of insomnia, depression, general anxiety, nightmares, headache and substance use, stratified by injury severity, were derived. Univariate logistic regression was used to examine unadjusted effects for each behavioural health problem and insomnia by injury severity. RESULTS: Participants were primarily male, < 30 years old and high school educated. Twenty-nine per cent met study criteria for insomnia; those with mild TBI were significantly more likely to meet criteria (43%) than those with moderate/severe TBI (22%), χ(2)(1, n = 112) = 5.088, p ≤ 0.05. Univariable logistic regression analyses revealed depressive symptoms and general anxiety were significantly associated with insomnia symptoms after TBI of any severity. Headache and binge drinking were significantly inversely related to insomnia symptoms after moderate/severe TBI, but not MTBI. CONCLUSIONS: Veterans with history of TBI, of any severity, and current insomnia symptoms may be at increased risk for depression and anxiety 1 year after TBI.

Long-term resting EEG correlates of repetitive mild traumatic brain injury and loss of consciousness: alterations in alpha-beta power.

Objective: Long-term changes to EEG spectra after mild traumatic brain injury (mTBI, i.e., concussion) have been reported; however, the role of injury characteristics in long-term EEG changes is unclear. It is also unclear how any chronic EEG changes may underlie either subjective or objective cognitive difficulties, which might help explain the variability in recovery after mTBI. Methods: This study included resting-state high-density electroencephalography (EEG) and mTBI injury data from 340 service members and veterans collected on average 11 years after injury as well as measures of objective and subjective cognitive functioning. The average absolute power within standard bands was computed across 11 spatial regions of the scalp. To determine how variation in brain function was accounted for by injury characteristics and aspects of cognition, we used regression analyses to investigate how EEG power was predicted by mTBI history characteristics [number, number with post-traumatic amnesia and witnessed loss of consciousness (PTA + LOC), context of injury (combat or non-combat), potentially concussive blast exposures], subjective complaints (TBIQOL General Cognitive and Executive Function Concerns), and cognitive performance (NIH Toolbox Fluid Intelligence and premorbid IQ). Results: Post-traumatic amnesia (PTA) and loss of consciousness (LOC), poorer cognitive performance, and combat experience were associated with reduced power in beta frequencies. Executive function complaints, lower premorbid IQ, poorer cognitive performance, and higher psychological distress symptoms were associated with greater power of delta frequencies. Multiple regression confirmed the relationship between PTA + LOC, poor cognitive performance, cognitive complaints, and reduced power in beta frequencies and revealed that repetitive mTBI was associated with a higher power in alpha and beta frequencies. By contrast, neither dichotomous classification of the presence and absence of mTBI history nor blast exposures showed a relationship with EEG power variables. Conclusion: Long-term alterations in resting EEG spectra measures of brain function do not appear to reflect any lasting effect of a history of mTBI or blast exposures. However, power in higher frequencies reflects both injury characteristics and subjective and objective cognitive difficulties, while power in lower frequencies is related to cognitive functions and psychological distress associated with poor long-term outcomes after mTBI.

Evaluating the Contribution of EEG Power Profiles to Characterize and Discriminate Posttraumatic Stress Symptom Factors in a Combat-Exposed Population.

This study investigated the use of resting-state electroencephalography (EEG) data to help differentiate posttraumatic stress disorder (PTSD) symptom factors. The sample, 147 combat-exposed OIF/OEF (Operation Iraqi Freedom/Operation Enduring Freedom) Veterans and service members, was a polytrauma population with variable PTSD and mild traumatic brain injury (mTBI) diagnoses. Participants completed the PTSD Checklist (PCL) and resting-state EEG was assessed for 10 minutes, with eyes closed. Regional averages of absolute power in alpha, beta, delta, and theta frequency bands were computed to estimate a single EEG common factor per band. An oblique 4 common-factor model was then fit to the 17 PCL items that included a residual EEG factor as an exogenous predictor with the group mean effect of mTBI on the EEG factor removed. Separate comparative model testing sequences for the alpha, beta, delta, and theta EEG factor frequency bands were conducted. An inverse relationship of delta and theta frequency bands on avoidance and numbing symptom factors (but not re-experiencing and hyperarousal) was found. Results provide evidence for possible neurobiological basis for the 4 PTSD symptom factors.

Distinction in EEG slow oscillations between chronic mild traumatic brain injury and PTSD.

Spectral information from resting state EEG is altered in acute mild traumatic brain injury (mTBI) and in disorders of consciousness, but there is disagreement about whether mTBI can elicit long term changes in the spectral profile. Even when identified, any long-term changes attributed to TBI can be confounded by psychiatric comorbidities such as PTSD, particularly for combat-related mTBI where postdeployment distress is commonplace. To address this question, we measured spectral power during the resting state in a large sample of service members and Veterans varying in mTBI history and active PTSD diagnosis but matched for having had combat blast exposure. We found that PTSD was associated with decreases in low frequency power, especially in the right temporoparietal region, while conversely, blast-related mTBI was associated with increases in low frequency power, especially in prefrontal and right temporal areas. Results support the idea that long-term neurophysiological effects of mTBI share some features with states of reduced arousal and cognitive dysfunction, suggesting a role for EEG in tracking the trajectory of recovery and persisting vulnerabilities to injury. Additionally, results suggest that EEG power reflects distinct pathophysiologies for current PTSD and chronic mTBI.

Laboratory impulsivity and depression in blast-exposed military personnel with post-concussion syndrome.

In military populations, traumatic brain injury (TBI) also holds potential to increase impulsivity and impair mood regulation due to blast injury effects on ventral frontal cortex - to put military personnel at risk for suicide or substance abuse. We assessed a linkage between depression and impaired behavioral inhibition in 117 blast-exposed service members (SM) and veterans with post-concussion syndrome (PCS), where PCS was defined using a Rivermead Postconcussive Symptom Questionnaire (RPQ) modified to clarify whether each symptom worsened compared to pre-blast. Center for Epidemiological Studies-Depression Scale (CES-D) scores, PTSD Checklist 5 (PCL-5) scores, and RPQ raw subscale scores correlated positively with commission and perseverative errors on the continuous performance test II (CPT-II). In contrast, the number of RPQ symptoms ostensibly worsened post-blast did not correlate with impulsive errors on the CPT-II. These data replicate earlier findings that link increased affective symptomatology to impaired behavior inhibition in military TBI populations, but where additional effects on impulsivity from the blast itself remain equivocal.

Sensorintegrative dysfunction underlying vestibular disorders after traumatic brain injury: a review.

Vestibular symptoms are persistent and problematic sequelae of blast exposure. Several lines of evidence suggest that these symptoms often stem from injury to the central nervous system. Current methods of assessing the vestibular system have described vestibular deficits that follow traumatic brain injury and differentiate blunt and blast trauma but have not examined the full range of vestibular functions that depend on the cerebral structures above the midbrain. Damage to the central vestibular circuits can lead to deficits in vital processes of spatial perception and navigation, in addition to dizziness and disequilibrium, and may also affect emotional functioning, particularly noradrenergically modulated states of anxiety. Perceptual functions can be assessed to determine the extent of central nervous system involvement in vestibular symptoms and to provide greater confidence when vestibular dysfunction is to be excluded. The ability to detect central vestibular dysfunction will significantly enhance our response to the dizziness and balance symptoms that are a common source of distress for Veterans.