A Comparison of Generalized and Individualized Vestibular Rehabilitation Therapy in a Military TBI Sample.

OBJECTIVE: To compare clinical outcomes between active duty service members receiving generalized versus individualized vestibular rehabilitation treatment (GVRT and IVRT, respectively) for persistent vestibular-related symptoms following mild traumatic brain injury (mTBI). SETTING: An outpatient TBI rehabilitation clinic. PARTICIPANTS: Fifty-seven participants with persistent vestibular-related symptoms following mTBI were randomly assigned to the GVRT ( n = 28) or IVRT ( n = 29) group, stratified by dizziness-related impairment severity. Forty-two participants ( n = 21 per group) completed the posttreatment evaluation and were included in analyses. DESIGN: We employed a single-site, randomized, pre-/posttest experimental design. The GVRT program consisted of eight 45-minute group-based treatment sessions and IVRT consisted of three 30-minute one-on-one treatment sessions both to be completed within 8 weeks. Group assignment was not blinded to study personnel or participants. Research evaluations were completed approximately 2 weeks prior to treatment initiation and following treatment completion. MAIN MEASURES: Outcome measures included Dizziness Handicap Inventory (DHI) and Activities-specific Balance Confidence Scale (ABC) total scores, Sensory Organization Test (SOT) composite equilibrium and sensory input ratio scores, Head Shake SOT (HS-SOT) conditions 2 and 5, and horizontal and vertical Dynamic Visual Acuity. Separate mixed-effects models were used to compare clinical outcomes between the GVRT and IVRT groups. RESULTS: Both groups demonstrated significant improvement from pre- to posttreatment on self-reported dizziness-related impairment (DHI [ F(1,41) = 16.28, P < .001]) and balance performance with and without head movement (composite equilibrium score [ F(1,41) = 16.58, P < .001, effect size [ES] = 0.43], somatosensory [ F(1,41) = 6.79, P = .013, ES = 0.26], visual [ F(1,41) = 6.49, P = .015, ES = 0.29], vestibular [ F(1,41) = 22.31, P < .001, ES = 0.55], and HS-SOT condition 5 [ F(1,38) = 23.98, P < .001, ES = 0.64]). Treatment effects did not differ between groups on any of the outcome measures. CONCLUSIONS: We provide preliminary evidence that differences in clinical outcomes do not exist between participants receiving generalized versus individualized VR. Further research is needed to determine comparative effectiveness between these 2 treatment approaches for persistent vestibular-related symptoms following mTBI.

Changes in attentional processing following neurofeedback in patients with persistent post-concussive symptoms: a pilot study.

OBJECTIVE: Persistent post-concussive symptoms (PPCS) often include attention deficits, particularly orienting and executive attention. Research in other clinical populations has demonstrated that neurofeedback therapy (NFT) is effective at improving orienting and executive attention, although its effects on attentional networks in patients with PPCS are unknown. METHOD: In this single-group pilot study, we examined attention-related event-related potentials (ERPs) - N1 and P3 - and cognitive outcomes following Live Z-score training (LZT), a variant of NFT. RESULTS: No changes in early selective attention, as indexed by N1 amplitude, were observed; however, P3 amplitude, which indexes neural resource allocation, increased following LZT and returned to baseline by 3 months. Cognitive performance improved following treatment, which was sustained at 3 months. The magnitude of change in P3 and ANT performance did not differ between orienting or executive attention, suggesting LZT improved general attentional processing efficiency. CONCLUSION: Our results suggest that LZT may positively affect attention globally, but does not target specific attention networks. These pilot data warrant the initiation of a clinical trial evaluating the effectiveness of LZT for treating attention deficits in patients with PPCS.

Saccadic impairment in chronic traumatic brain injury: examining the influence of cognitive load and injury severity.

OBJECTIVE: Previous research suggests that saccadic eye movements can be uniquely sensitive to impairment in chronic traumatic brain injury (TBI). This study was conducted to examine saccadic eye movements across varying levels of cognitive load and TBI history/severity. We hypothesized that saccadic impairment in chronic mild and moderate-severe TBI would be most pronounced under conditions of high cognitive load. METHODS: In total, 61 participants (including n = 20 with chronic mild TBI, n = 15 with chronic moderate-severe TBI, and 26 uninjured controls) completed a battery of conventional neuropsychological tests and the Fusion n-Back Test, which measures manual and saccadic response time (RT) across varying cognitive load and cueing conditions. RESULTS: Consistent with our hypotheses, chronic mild and moderate-severe TBI were associated with substantial saccadic impairment under conditions of high cognitive load. Participants with moderate-severe TBI also demonstrated saccadic impairment at low levels of cognitive load. TBI groups and uninjured controls did not differ significantly on manual metrics or conventional neuropsychological measures. CONCLUSIONS: This study provides additional support for the value of eye tracking for enhanced assessment of TBI. Additionally, findings suggest that TBI is associated with greatest susceptibility to oculomotor interference under high levels of cognitive load.

Electrophysiological correlates of error initiation and response correction.

Adaptive, goal-directed behavior requires the ability to monitor the perception-action cycle, detect errors, and make adjustments to restore volitional action. One limiting factor in gaining a clearer understanding of the functional significance of the neural correlates of error detection has been the predominant use of discrete responses (e.g., a button press) as measures of behavior that do not easily afford an assessment of online error correction. This limitation was addressed in the current study by examining the neural correlates of error initiation and correction with respect to dynamic cursor movements that permitted measurement of the initiation and correction of errant responses within individual trials. Results indicate that the ERN may reflect a general error alarm following the initiation of an error but that the Pe component may be more closely related to the initiation of corrective action. The data also reveal that the amplitude and latency of frontal midline Theta oscillations may be more closely related to corrective action, suggesting that error detection and corrective action are mediated by an overlapping neural network.

Changes in EEG Activity Following Live Z-Score Training Predict Changes in Persistent Post-concussive Symptoms: An Exploratory Analysis.

A specific variant of neurofeedback therapy (NFT), Live Z-Score Training (LZT), can be configured to not target specific EEG frequencies, networks, or regions of the brain, thereby permitting implicit and flexible modulation of EEG activity. In this exploratory analysis, the relationship between post-LZT changes in EEG activity and self-reported symptom reduction is evaluated in a sample of patients with persistent post-concussive symptoms (PPCS). Penalized regressions were used to identify EEG metrics associated with changes in physical, cognitive, and affective symptoms; the predictive capacity of EEG variables selected by the penalized regressions were subsequently validated using linear regression models. Post-treatment changes in theta/alpha ratio predicted reduction in pain intensity and cognitive symptoms and changes in beta-related power metrics predicted improvements in affective symptoms. No EEG changes were associated with changes in a majority of physical symptoms. These data highlight the potential for NFT to target specific EEG patterns to provide greater treatment precision for PPCS patients. This exploratory analysis is intended to promote the refinement of NFT treatment protocols to improve outcomes for patients with PPCS.

The Non-Concordance of Self-Reported and Performance-Based Measures of Vestibular Dysfunction in Military and Civilian Populations Following TBI.

As a predominately young, physically active, and generally healthy population, service members (SMs) with vestibular dysfunction (VD) following a TBI may not be accurately represented by the current civilian reference ranges on assessments of VD. This study enrolled SMs who were referred for vestibular rehabilitation following a mild/moderate TBI. The participants self-reported VD using the Activities-specific Balance Confidence (ABC) scale and the Dizziness Handicap Inventory (DHI) followed by evaluation of vestibular performance using computerized dynamic posturography sensory organizational test (CDP−SOT). Retrospective analysis of these outcomes comparing the study sample of SMs to the reported civilian samples revealed SMs self-reported lower VD with significantly higher balance confidence (ABC: 77.11 ± 14.61, p < 0.05) and lower dizziness (DHI: 37.75 ± 11.74, p < 0.05) than civilians. However, the SMs underperformed in performance-based evaluations compared to civilians with significantly lower CDP−SOT composite and ratio scores (COMP: 68.46 ± 13.46, p < 0.05; VIS: 81.36 ± 14.03, p < 0.01; VEST: 55.63 ± 22.28, p < 0.05; SOM: 90.46 ± 10.17, p < 0.05). Correlational analyses identified significant relationships between the ABC and CDP−SOT composite (r = 0.380, p < 0.01) and ratio scores (VIS: r = 0.266, p < 0.05; VEST: r = 0.352, p < 0.01). These results highlight the importance of recognizing and understanding nuances in assessing VD in SMs to ensure they have access to adequate care and rehabilitation prior to returning to duty.

Apolipoprotein E e4 is associated with worse self-reported neurobehavioral symptoms following uncomplicated mild traumatic brain injury in U.S. military service members.

Past research has found a relationship between the apolipoprotein E (APOE) e4 allele and worse neurobehavioral functioning following mild traumatic brain injury (MTBI) in civilian populations. The purpose of this study was to examine this relationship in service members and veterans (SMVs) following MTBI. Participants were 151 SMVs (103 uncomplicated MTBI; 48 Injured Controls [IC]) prospectively enrolled in the DVBIC-TBICoE 15-Year Longitudinal TBI Study. Participants completed a battery of self-reported neurobehavioral symptom measures on average 76.2 months post-injury (SD = 31.8). APOE genotyping was undertaken using non-fasting blood samples. Participants were classified into four subgroups based on injury (MTBI vs. IC) and APOE e4 allele status (e4 present/absent). In the IC group, there were no significant differences across APOE e4 status subgroups for all measures. In the MTBI group, participants with the APOE e4 allele had significantly worse scores on measures of depression, pain, anxiety, grief, positive well-being, social participation, and resilience compared to those without the e4 allele (d = .44 to d = .69). When comparing the number of 'clinically elevated' neurobehavioral measures simultaneously, the MTBI/e4 present subgroup consistently had a higher number of elevated measures compared to the MTBI/e4 absent, IC/e4 present, and IC/e4 absent subgroups. The APOE e4 allele was associated with poorer neurobehavioral outcome in SMVs in the chronic phase of recovery following MTBI. APOE e4 could be incorporated into screening tools to predict SMVs at risk for poor long-term neurobehavioral outcome in an effort to provide early intervention to improve long-term clinical outcome.

Semi-Automated Neurofeedback Therapy for Persistent Postconcussive Symptoms in a Military Clinical Setting: A Feasibility Study.

INTRODUCTION: Neurofeedback therapy (NFT) has demonstrated effectiveness for reducing persistent symptoms following traumatic brain injury (TBI); however, its reliance on NFT experts for administration and high number of treatment sessions limits its use in military medicine. Here, we assess the feasibility of live Z-score training (LZT)-a variant of NFT that requires fewer treatment sessions and can be administered by nonexperts-for use in a military clinical setting. MATERIALS AND METHODS: A single group design feasibility study was conducted to assess acceptability, tolerance, treatment satisfaction, and change in symptoms after a 6-week LZT intervention in 38 Service Members (SMs) with persistent symptoms comorbid with or secondary to mild TBI. Acceptance and feasibility were assessed using treatment completion and patients' satisfaction with treatment. To evaluate changes in symptom status, a battery of self-report questionnaires was administered at baseline, posttreatment, and 3-month follow-up to evaluate changes in psychological, neurobehavioral, sleep, pain, and headache symptoms, as well as self-efficacy in symptom management and life satisfaction. RESULTS: Participants tolerated the treatment well and reported a positive experience. Symptom improvement was observed, including depressive, neurobehavioral, and pain-related symptoms, with effects sustained at 3-month follow-up. CONCLUSION: LZT treatment appears to be a feasible, non-pharmacological therapy amenable to SMs. Results from this pilot study promote further investigation of LZT as an intervention for SMs with persistent symptoms following TBI.

Insights into cognitive pupillometry: Evaluation of the utility of pupillary metrics for assessing cognitive load in normative and clinical samples.

Despite increasing use of pupillometry to understand cognitive deficits in clinical populations, there is no consensus on what pupillary metrics are most useful. In this study, we compare the reliability, sensitivity to mild traumatic brain injury (TBI) and cognitive load differences, and the likelihood of replication between various pupillary metrics. Raw pupil diameter was recorded from 15 patients with chronic mild TBI and 23 uninjured controls while they performed a cognitive task with three levels of cognitive load. Several pupillary metrics were quantified from the pupillary data and submitted to tests of internal consistency, group ∗ cognitive load repeated measures ANOVAs, and bootstrapping analyses of effect size. Most pupillary metrics demonstrated acceptable, good, or excellent reliability. Metrics differed in sensitivity to group, cognitive load, and their interaction. Bootstrapping analyses revealed that peak-based metrics are more likely to replicate than means- or ratio-based metrics. Several pupillary metrics were determined to have great utility for measuring cognitive load in clinical or normative samples. This study directly addresses a known methodological gap in the cognitive pupillometry literature.

Increased risk for age-related impairment in visual attention associated with mild traumatic brain injury: Evidence from saccadic response times.

It was hypothesized that risk for age-related impairment in attention would be greater among those with remote history of mild TBI than individuals without history of head injury. Twenty-seven adults with remote history of mild TBI and a well-matched comparison group of 54 uninjured controls completed a computerized test of visual attention while saccadic and manual response times were recorded. Within the mild TBI group only, older age was associated with slower saccadic responses and poorer saccadic inhibition. Saccadic slowing was mitigated in situations where the timing and location of attention targets was fully predictable. Mild TBI was not associated with age-related increases in risk for neuropsychological impairment or neurobehavioral symptoms. These results provide preliminary evidence that risk for age-related impairment in visual attention may be higher among those with a history of mild TBI. Saccadic measures may provide enhanced sensitivity to this subtle form of cognitive impairment.

Multimodal assessment of visual attention using the Bethesda Eye & Attention Measure (BEAM).

INTRODUCTION: Computerized cognitive tests measuring manual response time (RT) and errors are often used in the assessment of visual attention. Evidence suggests that saccadic RT and errors may also provide valuable information about attention. This study was conducted to examine a novel approach to multimodal assessment of visual attention incorporating concurrent measurements of saccadic eye movements and manual responses. METHOD: A computerized cognitive task, the Bethesda Eye & Attention Measure (BEAM) v.34, was designed to evaluate key attention networks through concurrent measurement of saccadic and manual RT and inhibition errors. Results from a community sample of n = 54 adults were analyzed to examine effects of BEAM attention cues on manual and saccadic RT and inhibition errors, internal reliability of BEAM metrics, relationships between parallel saccadic and manual metrics, and relationships of BEAM metrics to demographic characteristics. RESULTS: Effects of BEAM attention cues (alerting, orienting, interference, gap, and no-go signals) were consistent with previous literature examining key attention processes. However, corresponding saccadic and manual measurements were weakly related to each other, and only manual measurements were related to estimated verbal intelligence or years of education. CONCLUSIONS: This study provides preliminary support for the feasibility of multimodal assessment of visual attention using the BEAM. Results suggest that BEAM saccadic and manual metrics provide divergent measurements. Additional research will be needed to obtain comprehensive normative data, to cross-validate BEAM measurements with other indicators of neural and cognitive function, and to evaluate the utility of these metrics within clinical populations of interest.

Evaluation of a clinically practical, ERP-based neurometric battery: Application to age-related changes in brain function.

OBJECTIVE: Event-related potentials (ERPs) show promise as markers of neurocognitive dysfunction, but conventional recording procedures render measurement of many ERP-based neurometrics clinically impractical. The purpose of this work was (a) to develop a brief neurometric battery capable of eliciting a broad profile of ERPs in a single, clinically practical recording session, and (b) to evaluate the sensitivity of this neurometric profile to age-related changes in brain function. METHODS: Nested auditory stimuli were interleaved with visual stimuli to create a 20-min battery designed to elicit at least eight ERP components representing multiple sensory, perceptual, and cognitive processes (Frequency & Gap MMN, P50, P3, vMMN, C1, N2pc, and ERN). Data were recorded from 21 younger and 21 high-functioning older adults. RESULTS: Significant multivariate differences were observed between ERP profiles of younger and older adults. Metrics derived from ERP profiles could be used to classify individuals into age groups with a jackknifed classification accuracy of 78.6%. CONCLUSIONS: Results support the utility of this design for neurometric profiling in clinical settings. SIGNIFICANCE: This study demonstrates a method for measuring a broad profile of ERP-based neurometrics in a single, brief recording session. These markers may be used individually or in combination to characterize/classify patterns of sensory and/or perceptual brain function in clinical populations.