Temporoparietal encoding of space and time during vestibular-guided orientation

When we walk in our environment, we readily determine our travelled distance and location using visual cues. In the dark, estimating travelled distance uses a combination of somatosensory and vestibular (i.e., inertial) cues. The observed inability of patients with complete peripheral vestibular failure to update their angular travelled distance during active or passive turns in the dark implies a privileged role for vestibular cues during human angular orientation. As vestibular signals only provide inertial cues of self-motion (e.g., velocity, °/s), the brain must convert motion information to distance information (a process called 'path integration') to maintain our spatial orientation during self-motion in the dark. It is unknown, however, what brain areas are involved in converting vestibular-motion signals to those that enable such vestibular-spatial orientation. Hence, using voxel-based lesion-symptom mapping techniques, we explored the effect of acute right hemisphere lesions in 18 patients on perceived angular position, velocity and motion duration during whole-body angular rotations in the dark. First, compared to healthy controls' spatial orientation performance, we found that of the 18 acute stroke patients tested, only the four patients with damage to the temporoparietal junction showed impaired spatial orientation performance for leftward (contralesional) compared to rightward (ipsilesional) rotations. Second, only patients with temporoparietal junction damage showed a congruent underestimation in both their travelled distance (perceived as shorter) and motion duration (perceived as briefer) for leftward compared to rightward rotations. All 18 lesion patients tested showed normal self-motion perception. These data suggest that the cerebral cortical regions mediating vestibular-motion ('am I moving?') and vestibular-spatial perception ('where am I?') are distinct. Furthermore, the congruent contralesional deficit in time (motion duration) and position perception, seen only in temporoparietal junction patients, may reflect a common neural substrate in the temporoparietal junction that mediates the encoding of motion duration and travelled distance during vestibular-guided navigation. Alternatively, the deficits in timing and spatial orientation with temporoparietal junction lesions could be functionally linked, implying that the temporoparietal junction may act as a cortical temporal integrator, combining estimates of self-motion velocity over time to derive an estimate of travelled distance. This intriguing possibility predicts that timing abnormalities could lead to spatial disorientation

The effect of pedunculopontine nucleus deep brain stimulation on postural sway and vestibular perception

© 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of Europe an Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and re production in any medium, provided the original work is properly cited, see https://creativecommons.org/licenses/by/3.0/BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) reduces the number of falls in patients with Parkinson's disease (PD). It was hypothesized that enhanced sensory processing contributes to this PPN-mediated gait improvement. METHODS: Four PD patients (and eight matched controls) with implanted bilateral PPN and subthalamic nucleus DBS electrodes were assessed on postural (with/without vision) and vestibular perceptual threshold tasks. RESULTS: Pedunculopontine nucleus ON stimulation (compared to OFF) lowered vestibular perceptual thresholds but there was a disproportionate increase in the normal sway increase on going from light to dark. CONCLUSIONS: The disproportionate increased sway with PPN stimulation in the dark may paradoxically improve balance function since mechanoreceptor signals rapidly adapt to continuous pressure stimulation from postural akinesia. Additionally, the PPN-mediated vestibular signal enhancement also improves the monitoring of postural sway. Overall, PPN stimulation may improve sensory feedback and hence balance performance.Peer reviewedFinal Published versio

Vestibular Perception following Acute Unilateral Vestibular Lesions.

Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

Functional neuroimaging of visuo-vestibular interaction

The brain combines visual, vestibular and proprioceptive information to distinguish between self- and world motion. Often these signals are complementary and indicate that the individual is moving or stationary with respect to the surroundings. However, conflicting visual motion and vestibular cues can lead to ambiguous or false sensations of motion. In this study, we used functional magnetic resonance imaging to explore human brain activation when visual and vestibular cues were either complementary or in conflict. We combined a horizontally moving optokinetic stimulus with caloric irrigation of the right ear to produce conditions where the vestibular activation and visual motion indicated the same (congruent) or opposite directions of self-motion (incongruent). Visuo-vestibular conflict was associated with increased activation in a network of brain regions including posterior insular and transverse temporal areas, cerebellar tonsil, cingulate and medial frontal gyri. In the congruent condition, there was increased activation in primary and secondary visual cortex. These findings suggest that when sensory information regarding self-motion is contradictory, there is preferential activation of multisensory vestibular areas to resolve this ambiguity. When cues are congruent, there is a bias towards visual cortical activation. The data support the view that a network of brain areas including the posterior insular cortex may play an important role in integrating and disambiguating visual and vestibular cues

Abnormal Visuo-vestibular Interactions in Vestibular Migraine: a Cross Sectional Study

Vestibular migraine is amongst the commonest causes of episodic vertigo. Chronically, patients with vestibular migraine develop abnormal responsiveness to both vestibular and visual stimuli characterised by heightened self-motion sensitivity and visually-induced dizziness. Yet, the neural mechanisms mediating such symptoms remain unknown. We postulate that such symptoms are attributable to impaired visuo-vestibular cortical interactions, which in-turn disrupts normal vestibular function. To assess this, we investigated whether prolonged, full-field visual motion exposure, which has previously been shown to modulate visual cortical excitability in both healthy individuals and avestibular patients, could disrupt vestibular ocular reflex (VOR) and vestibular-perceptual thresholds of self-motion during rotations. Our findings reveal that vestibular migraine patients exhibited abnormally elevated reflexive and perceptual vestibular thresholds at baseline. Following visual motion exposure, both reflex and perceptual thresholds were significantly further increased in vestibular migraine patients relative to healthy controls, migraineurs without vestibular symptoms and patients with episodic vertigo due to a peripheral inner-ear disorder. Our results provide support for the notion of altered visuo-vestibular cortical interactions in vestibular migraine, as evidenced by vestibular threshold elevation following visual motion exposure

Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p <\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials

COPD exacerbation: Lost in translation

The introduction and acceptance of a standard definition for exacerbations of COPD can be helpful in prompt diagnosis and management of these events. The latest GOLD executive committee recognised this necessity and it has now included a definition of exacerbation in the guidelines for COPD which is an important step forward in the management of the disease. This definition is pragmatic and compromises the different approaches for exacerbation. However, the inclusion of the "healthcare utilisation" approach (".. may warrant a change in regular medication") in the definition may introduce in the diagnosis of exacerbation factors related to the access to health care services which may not be related to the underlying pathophysiologal process which characterizes exacerbations. It should be also noted that the aetiology of COPD exacerbations has not yet been included in the current definition. In this respect, the definition does not acknowledge the fact that many patients with COPD may suffer from additional conditions (i.e. congestive cardiac failure or pulmonary embolism) that can masquerade as exacerbations but they should not be considered as causes of them. The authors therefore suggest that an inclusion of the etiologic factors of COPD exacerbations in the definition. Moreover, COPD exacerbations are characterized by increased airway and systemic inflammation and significant deterioration in lung fuction. These fundamental aspects should be accounted in diagnosis/definition of exacerbations. This could be done by the introduction of a "laboratory" marker in the diagnosis of these acute events. The authors acknowledge that the use of a test or a biomarker in the diagnosis of exacerbations meets certain difficulties related to performing lung function tests or to sampling during exacerbations. However, the introduction of a test that reflects airway or systemic inflammation in the diagnosis of exacerbations might be another step forward in the management of COPD