Brain Mechanisms Explaining Postural Imbalance in Traumatic Brain Injury: A Systematic Review.

Introduction: Persisting imbalance and falls in community-dwelling traumatic brain injury (TBI) survivors are linked to reduced long-term survival. However, a detailed understanding of the impact of TBI upon the brain mechanisms mediating imbalance is lacking. To understand the state of the art concerning the brain mechanisms mediating imbalance in TBI, we performed a systematic review of the literature. Methods: PubMed, Web of Science, and Scopus were searched and peer-reviewed research articles in humans, with any severity of TBI (mild, moderate, severe, or concussion), which linked a postural balance assessment (objective or subjective) with brain imaging (through computed tomography, T1-weighted imaging, functional magnetic resonance imaging [fMRI], resting-state fMRI, diffusion tensor imaging, magnetic resonance spectroscopy, single-photon emission computed tomography, electroencephalography, magnetoencephalography, near-infrared spectroscopy, and evoked potentials) were included. Out of 1940 articles, 60 were retrieved and screened, and 25 articles fulfilling inclusion criteria were included. Results: The most consistent finding was the link between imbalance and the cerebellum; however, the regions within the cerebellum were inconsistent. Discussion: The lack of consistent findings could reflect that imbalance in TBI is due to a widespread brain network dysfunction, as opposed to focal cortical damage. The inconsistency in the reported findings may also be attributed to heterogeneity of methodology, including data analytical techniques, small sample sizes, and choice of control groups. Future studies should include a detailed clinical phenotyping of vestibular function in TBI patients to account for the confounding effect of peripheral vestibular disorders on imbalance and brain imaging.

Electrophysiological markers of vestibular-mediated self-motion perception - A pilot study.

Peripheral vestibular activation results in multi-level responses, from brainstem-mediated reflexes (e.g. vestibular ocular reflex - VOR) to perception of self-motion. While VOR responses indicate preserved vestibular peripheral and brainstem functioning, there are no automated measures of vestibular perception of self-motion - important since some patients with brain disconnection syndromes manifest a vestibular agnosia (intact VOR but impaired self-motion perception). Electroencephalography ('EEG') - may provide a surrogate marker of vestibular perception of self-motion. A related objective is obtaining an EEG marker of vestibular sensory signal processing, distinct from vestibular-motion perception. We performed a pilot study comparing EEG responses in the dark when healthy participants sat in a vibrationless computer-controlled motorised rotating chair moving at near threshold of self-motion perception, versus a second situation in which subjects sat in the chair at rest in the dark who could be induced (or not) into falsely perceiving self-motion. In both conditions subjects could perceive self-motion perception, but in the second there was no bottom-up reflex-brainstem activation. Time-frequency analyses showed: (i) alpha frequency band activity is linked to vestibular sensory-signal activation; and (ii) theta band activity is a marker of vestibular-mediated self-motion perception. Consistent with emerging animal data, our findings support the role of theta activity in the processing of self-motion perception.

Vestibular prepulse inhibition of the human blink reflex.

OBJECTIVE: Auditory and somatosensory prepulses are commonly used to assess prepulse inhibition (PPI). The effect of a vestibular prepulse upon blink reflex excitability has not been hitherto assessed. METHODS: Twenty-two healthy subjects and two patients with bilateral peripheral vestibular failure took part in the study. Whole body yaw rotation in the dark provided a vestibular inertial prepulse. Blink reflex was electrically evoked after the end of the rotation. The amplitude of R1 and the area-under-the-curve (area) of the blink reflex R2 and R2c responses were recorded and analysed. RESULTS: A vestibular prepulse inhibited the R2 (p < 0.001) and R2c area (p < 0.05). Increasing the angular acceleration did not increase the R2 and R2c inhibition (p > 0.05). Voluntary suppression of the vestibulo-ocular reflex did not affect the magnitude of inhibition (p > 0.05). Patients with peripheral vestibular failure did not show any inhibition. CONCLUSIONS: Our data support a vestibular gating mechanism in humans. SIGNIFICANCE: The main brainstem nucleus mediating PPI - the pedunculopontine nucleus (PPN) - is heavily vestibular responsive, which is consistent with our findings of a vestibular-mediated PPI. Our technique may be used to interrogate the fidelity of brain circuits mediating vestibular-related PPN functions. Given the PPN's importance in human postural control, our technique may also provide a neurophysiological biomarker of balance.

Translocator protein PET imaging in temporal lobe epilepsy: A reliable test-retest study using asymmetry index.

Objective: Translocator protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy to assess the efficacy of novel therapeutics for targeting neuroinflammation. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here, we examine test-retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used as an endpoint in clinical trials for epilepsy. Methods: Five subjects with epilepsy and confirmed mesial temporal lobe sclerosis (mean age 36 years, 3 men) were scanned twice-on average 8 weeks apart-using a second generation TSPO targeting radioligand, [11C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [11C]PBR28 binding in these subjects and compared the results with 8 (mean age 45, 6 men) previously studied healthy volunteers. Results: The mean (± SD) of the volume of distribution (VT), of all subjects, in patients living with epilepsy for both test and retest scans on all regions of interest (ROI) is 4.49 ± 1.54 vs. 5.89 ± 1.23 in healthy volunteers. The bias between test and retest in an asymmetry index as a percentage was small (-1.5%), and reliability is demonstrated here with Bland-Altman Plots (test mean 1.062, retest mean 2.56). In subjects with epilepsy, VT of [11C]PBR28 is higher in the (ipsilateral) hippocampal region where sclerosis is present than in the contralateral region. Conclusion: When using TSPO PET in patients with epilepsy with hippocampal sclerosis (HS), an inter-hemispheric asymmetry index in the hippocampus is a measure with good test-retest reliability. We provide estimates of test-retest variability that may be useful for estimating power where group change in VT represents the clinical outcome.

Prevalence of stroke in acute vertigo presentations: A UK tertiary stroke centre perspective.

The reported prevalence of stroke amongst patients presenting to hospital with acute vertigo and/or imbalance is c. 5%, leading to the pervasive notion amongst emergency and stroke physicians, that stroke is uncommon in this cohort. To interrogate the veracity of this notion, we systematically and retrospectively screened the electronic care records in our institution of patients referred as suspected stroke, to a hyperacute stroke service at a large tertiary referral centre. We screened 24,310 consecutive patients' electronic case records presenting to our hospital as an emergency over a 4-month period, 332 of whom were referred as suspected stroke whose case records were assessed via structured review. Of these 332 cases, 61 presented with a vestibular syndrome, i.e. having at least one of imbalance, dizziness or vertigo. Of the 61 vestibular cases, 38 (62%) were diagnosed as stroke confirmed by imaging in 25/38 or upon clinical grounds only (13/38). None of the 38 vestibular stroke cases received thrombolysis or thrombectomy treatment. In a UK urban population (2.5mn), acute vestibular syndrome cases referred to stroke services have a 50% stroke prevalence. None of the vestibular stroke cases received hyperacute stroke treatment e.g., thrombolysis, due to delay in diagnosis. The high stroke prevalence in our cohort may indicate an excessively high threshold for referring acute vestibular cases for stroke, implying a high number of missed stroke cases. We suggest that early access to vestibular neurologists in acute vestibular cases should improve the proportion of vestibular stroke cases receiving definitive stroke treatment.

The human brain networks mediating the vestibular sensation of self-motion.

Vestibular Agnosia - where peripheral vestibular activation triggers the usual reflex nystagmus response but with attenuated or no self-motion perception - is found in brain disease with disrupted cortical network functioning, e.g. traumatic brain injury (TBI) or neurodegeneration (Parkinson's Disease). Patients with acute focal hemispheric lesions (e.g. stroke) do not manifest vestibular agnosia. Thus, brain network mapping techniques, e.g. resting state functional MRI (rsfMRI), are needed to interrogate functional brain networks mediating vestibular agnosia. Hence, we prospectively recruited 39 acute TBI patients with preserved peripheral vestibular function and obtained self-motion perceptual thresholds during passive yaw rotations in the dark and additionally acquired whole-brain rsfMRI in the acute phase. Following quality-control checks, 26 patient scans were analyzed. Using self-motion perceptual thresholds from a matched healthy control group, 11 acute TBI patients were classified as having vestibular agnosia versus 15 with normal self-motion perception thresholds. Using independent component analysis on the rsfMRI data, we found altered functional connectivity in bilateral lingual gyrus and temporo-occipital fusiform cortex in the vestibular agnosia patients. Moreover, regions of interest analyses showed both inter-hemispheric and intra-hemispheric network disruption in vestibular agnosia. In conclusion, our results show that vestibular agnosia is mediated by bilateral anterior and posterior network dysfunction and reveal the distributed brain mechanisms mediating vestibular self-motion perception.

The effect of galvanic vestibular stimulation on postural balance in Parkinson's disease: A systematic review and meta-analysis.

People with Parkinson's disease (PD) develop postural imbalance and falls. Galvanic Vestibular Stimulation (GVS) may potentially improve postural balance in humans and hence reduce falls in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD. Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges' g) as a measure of effect size in all studies. We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n = 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [- 0.17, 1.41], I2 = 96.21%). Egger's test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%). Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution.

The effects of unilateral transcranial direct current stimulation on unimanual laparoscopic peg-transfer task.

INTRODUCTION: Efficient training methods are required for laparoscopic surgical skills training to reduce the time needed for proficiency. Transcranial direct current stimulation (tDCS) is widely used to enhance motor skill acquisition and can be used to supplement the training of laparoscopic surgical skill acquisition. The aim of this study was to investigate the effect of anodal tDCS over the primary motor cortex (M1) on the performance of a unimanual variant of the laparoscopic peg-transfer task. METHODS: Fifteen healthy subjects participated in this randomized, double-blinded crossover study involving an anodal tDCS and a sham tDCS intervention separated by 48 h. On each intervention day, subjects performed a unimanual variant of laparoscopic peg-transfer task in three sessions (baseline, tDCS, post-tDCS). The tDCS session consisted of 10 min of offline tDCS followed by 10 min of online tDCS. The scores based on the task completion time and the number of errors in each session were used as a primary outcome measure. A linear mixed-effects model was used for the analysis. RESULTS: We found that the scores increased over sessions (p < 0.01). However, we found no effects of stimulation (anodal tDCS vs. sham tDCS) and no interaction of stimulation and sessions. CONCLUSION: This study suggests that irrespective of the type of current stimulation (anodal and sham) over M1, there was an improvement in the performance of the unimanual peg-transfer task, implying that there was motor learning over time. The results would be useful in designing efficient training paradigms and further investigating the effects of tDCS on laparoscopic peg-transfer tasks.