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.

Eye tracker outcomes in a randomized trial of 40 sessions of hyperbaric oxygen or sham in participants with persistent post concussive symptoms.

PURPOSE: Eye movements may offer a sensitive method to measure response to intervention in mild traumatic brain injury (mTBI). METHODS: The Brain Injury and Mechanisms of Action of Hyperbaric Oxygen for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury Study (BIMA) randomized 71 participants to 40 sessions of hyperbaric oxygen or sham. A companion normative study (Normal) enrolled 75 participants. An eye tracking system measured left and right eye movements for saccadic and smooth pursuit. At baseline two smooth pursuit tasks, circular and horizontal ramp, and four saccadic tasks, horizontal and vertical step, reading, and memory guided-on tasks differentiated BIMA from Normal participants. The change from baseline in these tasks were measured and compared between interventions and against Normal participants at 13 weeks and six-month follow-up using the two-sample t-test. The Holm-Bonferroni procedure was used to adjust for multiple testing. RESULTS: Change from baseline in eyetracker measures for participants assigned to the hyperbaric oxygen arm did not significantly differ from those assigned to the sham arm at post-randomization time points 13 weeks and six months. Consistent shifts of BIMA participant values toward Normal values at 13 weeks and six months were observed for overall fixation duration, forward saccadic duration, and number of lines read for the reading task, number of misses on the memory guided-on task, and absolute intersaccadic interval velocity and absolute saccadic amplitude on the circular task. The distributions between Normal and BIMA participants were no longer statistically significantly different at 13 weeks and six months post enrollment for these measures. CONCLUSION: The baseline differences between BIMA and Normal suggest potential vulnerability of the smooth pursuit system and the saccadic system. During the six-month follow-up period, improvement toward Normal was seen on some measures in both the hyperbaric oxygen and sham intervention arms without difference between intervention groups. IDS: clinicaltrials.gov Identifiers NCT01611194 and NCT01925963.

Eye Tracking Results in Postconcussive Syndrome Versus Normative Participants.

Purpose: Standard physical, neurologic, and neuropsychologic examinations may not detect abnormalities after mild traumatic brain injury (mTBI). An analysis of eye movements may be more sensitive to neurologic dysfunction. Methods: We performed eye tracking assessments in 71 active duty and veteran military personnel with persistent postconcussive symptoms (3 months to 5 years after mTBI) and 75 volunteers with no history of brain injury. Both eyes were sampled at 500 Hz and analyzed for various eye measurement parameters during visual tasks involving the saccadic and smooth systems. Results: No difference between mTBI and normal participants in main sequence profiles was observed. On the circular task, intersaccadic interval duration was shorter in mTBI compared with normal subjects (horizontal: Cohen's D = -0.65; vertical: Cohen's D = -0.75). For reading, absolute saccadic amplitudes (Cohen's D = -0.76) and average forward saccadic amplitudes were lower (Cohen's D = -0.61). Absolute fixation velocity was higher (Cohen's D = 1.02), and overall fixation durations (Cohen's D = 0.58), regression durations (Cohen's D = 0.49), and forward saccadic durations (Cohen's D=0.54) were longer. mTBI participants had more fixations (Cohen's D = 0.54) and regressions per line (Cohen's D = 0.70) and read fewer lines (Cohen's D = -0.38) than normal subjects. On the horizontal ramp task, mTBI participants had lower weighted smooth pursuit gains (Cohen's D = -0.55). On the horizontal step task, mTBI participants had shorter mean fixation times (Cohen's D = -0.55). Conclusions: These results suggest vulnerability of the smooth pursuit and saccadic systems in mTBI. Eye tracking shows promise as an objective, sensitive assessment of damage after mTBI. (ClinicalTrials.gov number, NCT01611194, NCT01925963.).

Differential eye movements in mild traumatic brain injury versus normal controls.

OBJECTIVES: Objective measures to diagnose and to monitor improvement of symptoms following mild traumatic brain injury (mTBI) are lacking. Computerized eye tracking has been advocated as a rapid, user friendly, and field-ready technique to meet this need. DESIGN: Eye-tracking data collected via a head-mounted, video-based binocular eye tracker was used to examine saccades, fixations, and smooth pursuit movement in military Service Members with postconcussive syndrome (PCS) and asymptomatic control subjects in an effort to determine if eye movement differences could be found and quantified. PARTICIPANTS: Sixty Military Service Members with PCS and 26 asymptomatic controls. OUTCOME MEASURES: The diagnosis of mTBI was confirmed by the study physiatrist's history, physical examination, and a review of any medical records. Various features of saccades, fixation and smooth pursuit eye movements were analyzed. RESULTS: Subjects with symptomatic mTBI had statistically larger position errors, smaller saccadic amplitudes, smaller predicted peak velocities, smaller peak accelerations, and longer durations. Subjects with symptomatic mTBI were also less likely to follow a target movement (less primary saccades). In general, symptomatic mTBI tracked the stepwise moving targets less accurately, revealing possible brain dysfunction. CONCLUSIONS: A reliable, standardized protocol that appears to differentiate mTBI from normals was developed for use in future research. This investigation represents a step toward objective identification of those with PCS. Future studies focused on increasing the specificity of eye movement differences in those with PCS are needed.

Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury.

The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (TBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between and within groups testing of pre- and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mild TBI when compared with a sham-control.

Experimental support that ocular tremor in Parkinson's disease does not originate from head movement.

INTRODUCTION: Our recent report of ocular tremor in Parkinson's disease (PD) has raised considerable controversy as to the origin of the tremor. Using an infrared based eye tracker and a magnetic head tracker, we reported that ocular tremor was recordable in PD subjects with no apparent head tremor. However, other investigators suggest that the ocular tremor may represent either transmitted appendicular tremor or subclinical head tremor inducing the vestibulo-ocular reflex (VOR). The present study aimed to further investigate the origin of ocular tremor in PD. METHODS: Eye movements were recorded in 8 PD subjects both head free, and with full head restraint by means of a head holding device and a dental impression bite plate. Head movements were recorded independently using both a high sensitivity tri-axial accelerometer and a magnetic tracking system, each synchronized to the eye tracker. RESULTS: Ocular tremor was observed in all 8 PD subjects and was not influenced by head free and head fixed conditions. Both magnetic tracking and accelerometer recordings supported that the ocular tremor was fully independent of head position. CONCLUSION: The present study findings support our initial findings that ocular tremor is a fundamental feature of PD unrelated to head movements. Although the utility of ocular tremor for diagnostic purposes requires validation, current findings in large cohorts of PD subjects suggest its potential as a reliable clinical biomarker.

Slowed saccades and increased square wave jerks in essential tremor.

BACKGROUND: Eye movements in essential tremor (ET) are poorly described and may present useful information on the underlying pathophysiology of the disorder. METHODS: Sixty patients with ET, including 15 de novo untreated patients, and 60 age-matched controls constitute the study population. A video-based eye tracker was used to assess binocular eye position. Oculomotor function was assessed while subjects followed random horizontally and vertically step-displaced targets. RESULTS: For all reflexive saccades, latencies were increased in ET subjects by a mean of 16.3% (p<0.01). Saccades showed reduced peak velocities with a lengthy, wavering velocity plateau, followed by slowed decelerations. For larger 30°+ saccades, peak velocities were decreased by a mean of 25.2% (p<0.01) and durations increased by 31.8% (p<0.01). The frequency of square wave jerks (SWJs) in patients was more than triple that of controls (p<0.0001). Despite frequent interruptions by SWJs, fixations were otherwise stable and indistinguishable from controls (root mean square [RMS] velocity, p = 0.324). The abnormal eye movement parameters were independent of disease duration, tremor severity, and medication therapy. DISCUSSION: In contrast to normally swift onset and efficient acceleration/deceleration movements, saccades in ET are characterized by abnormally prolonged latencies and slowed velocity profiles. Although ET subjects maintain highly stable fixations, they are interrupted by increased numbers of SWJs. This study reveals novel oculomotor deficits in ET, which are distinct from the eye movement dysfunction of other movement disorders, supporting a role for eye tracking to assist in the differential diagnoses of not only atypical, but also more common movement disorders.

Pervasive ocular tremor in patients with Parkinson disease.

OBJECTIVE: To further assess oculomotor control of patients with Parkinson disease (PD) during fixation and with movement. DESIGN: Case-control study. SETTING: A Parkinson disease research, education, and clinical center. PATIENTS One hundred twelve patients with PD, including 18 de novo untreated patients, and 60 age-matched controls. INTERVENTION: Modern, precise eye tracking technology was used to assess oculomotor parameters. Oculomotor function was compared between groups during fixation and while tracking a randomly displaced target on a PC monitor. MAIN OUTCOME MEASURES: Fixation stability and saccadic parameters. RESULTS: All patients with PD and 2 of 60 control subjects showed oscillatory fixation instability (ocular tremor), with an average fundamental frequency of 5.7 Hz and average magnitude of 0.27°. Saccadic parameters and occurrences of square wave jerks did not differ between subjects with PD and controls. The amplitude and frequency of fixation instability did not correlate with disease duration, clinical Unified Parkinson's Disease Rating Scale scores, or dopa-equivalent dosing. No differences in oculomotor parameters were found between medicated and unmedicated patients with PD. CONCLUSIONS: All patients with PD exhibited persistent ocular tremor that prevented stability during fixation. The pervasiveness and specificity of this feature suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing PD.

A pilot study of vitamin D and balance characteristics in middle-aged, healthy individuals.

OBJECTIVE: To examine what relationship exists between 25-hydroxyvitamin D (25-OHD) levels and postural competency in the middle-aged, healthy individual. DESIGN: A community convenience sample. SETTING: Major medical center employees. SUBJECTS: Thirty-five healthy individuals older than 40 years of age who demonstrated appropriate cognition and physical stability. Specific exclusion criteria included any prior history of hip, knee, or ankle fracture or surgery. METHODS: Questionnaire regarding exercise and sun exposure, vitamin D blood level, followed by computerized dynamic posturography (CDP) assessment of balance. MAIN OUTCOME MEASUREMENTS: CDP scores of individuals with normal and subnormal vitamin D levels. RESULTS: Thirteen male and 22 female subjects had a mean age of 56.0 years (standard deviation, 7.6; range, 42-77). Self-reported, retrospective mean weekly sun exposure was 7.36 hours (standard deviation, 6.4 hours). Twenty-six subjects (76.5%) described themselves as regular exercisers. Mean 25-OHD level for the sample was 21.5 ng/mL (standard deviation, 12.1 ng/mL). When subjects were divided into those with low and high 25-OHD levels, there was no significant difference in composite limits of stability reaction time scores (mean, 0.98 seconds and 0.84 seconds; P = .23), composite maximal velocity scores (4.2 degrees /second and 5.5 degrees /second; P = .08), composite end point excursion (70.3% and 70.1%; P = .95), and directional control composite scores (71.0% and 71.4%; P = .93). The two groups also showed no significant differences in rhythmic weight shifting left and right as well as forward and backward. CONCLUSIONS: Unlike studies involving elderly subjects, this study of younger, healthy subjects did not demonstrate a relationship between vitamin D and balance.