The influence of postural threat-induced anxiety on locomotor learning and updating.

The ability to adapt our locomotion in a feedforward (i.e., "predictive") manner is crucial for safe and efficient walking behavior. Equally important is the ability to quickly deadapt and update behavior that is no longer appropriate for the given context. It has been suggested that anxiety induced via postural threat may play a fundamental role in disrupting such deadaptation. We tested this hypothesis, using the "broken escalator" phenomenon: Fifty-six healthy young adults walked onto a stationary walkway ("BEFORE" condition, 5 trials), then onto a moving walkway akin to an airport travelator ("MOVING" condition, 10 trials), and then again onto the stationary walkway ("AFTER" condition, 5 trials). Participants completed all trials while wearing a virtual reality headset, which was used to induce postural threat-related anxiety (raised clifflike drop at the end of the walkway) during different phases of the paradigm. We found that performing the locomotor adaptation phase in a state of increased threat disrupted subsequent deadaptation during AFTER trials: These participants displayed anticipatory muscular activity as if expecting the platform to move and exhibited inappropriate anticipatory forward trunk movement that persisted during multiple AFTER trials. In contrast, postural threat induced during AFTER trials did not affect behavioral or neurophysiological outcomes. These findings highlight that actions learned in the presence of postural threat-induced anxiety are strengthened, leading to difficulties in deadapting these behaviors when no longer appropriate. Given the associations between anxiety and persistent maladaptive gait behaviors (e.g., "overly cautious" gait, functional gait disorders), the findings have implications for the understanding of such conditions.NEW & NOTEWORTHY Safe and efficient locomotion frequently requires movements to be adapted in a feedforward (i.e., "predictive") manner. These adaptations are not always correct, and thus inappropriate behavior must be quickly updated. Here we showed that increased threat disrupts this process. We found that locomotor actions learned in the presence of postural threat-induced anxiety are strengthened, subsequently impairing one's ability to update (or "deadapt") these actions when they are no longer appropriate for the current context.

Vascular neuro-otology: vestibular transient ischemic attacks and chronic dizziness in the elderly.

PURPOSE OF REVIEW: To explore the differential diagnosis of posterior fossa transient ischemic attacks (TIA) associated with vertigo and/or imbalance.To review the contribution of cerebral small vessel (SVD) disease to balance dysfunction and dizziness in the elderly. MAIN FINDINGS: TIAs involving vestibular structures that mediate the vestibulo-ocular and vestibulospinal reflexes remain a diagnostic challenge because they overlap with causes of benign episodic vertigo. Here, we summarize the results of multidisciplinary specialty efforts to improve timely recognition and intervention of peripheral and central vestibular ischemia. More papers confirm that SVD is a major cause of gait disability, falls and cognitive disorder in the elderly. Recent work shows that early stages of SVD may also be responsible for dizziness in the elderly. The predominant location of the white matter changes, in the frontal deep white matter and genu of the corpus callosum, explains the association between cognitive and balance dysfunction in SVD related symptoms. SUMMARY: The evaluation of patients with intermittent vascular vertigo represent a major diagnostic challenge, recent reviews explore the ideal design approach for a multidisciplinary study to increase early recognition and intervention. Hemispheric white matter microvascular ischemia has been the subject of research progress - advanced stages are known to cause gait disorder and dementia but early stages are associated with "idiopathic" dizziness in the elderly.

Dissociated cerebellar contributions to feedforward gait adaptation.

The cerebellum is important for motor adaptation. Lesions to the vestibulo-cerebellum selectively cause gait ataxia. Here we investigate how such damage affects locomotor adaptation when performing the 'broken escalator' paradigm. Following an auditory cue, participants were required to step from the fixed surface onto a moving platform (akin to an airport travellator). The experiment included three conditions: 10 stationary (BEFORE), 15 moving (MOVING) and 10 stationary (AFTER) trials. We assessed both behavioural (gait approach velocity and trunk sway after stepping onto the moving platform) and neuromuscular outcomes (lower leg muscle activity, EMG). Unlike controls, cerebellar patients showed reduced after-effects (AFTER trials) with respect to gait approach velocity and leg EMG activity. However, patients with cerebellar damage maintain the ability to learn the trunk movement required to maximise stability after stepping onto the moving platform (i.e., reactive postural behaviours). Importantly, our findings reveal that these patients could even initiate these behaviours in a feedforward manner, leading to an after-effect. These findings reveal that the cerebellum is crucial for feedforward locomotor control, but that adaptive locomotor behaviours learned via feedback (i.e., reactive) mechanisms may be preserved following cerebellum damage.

The human vestibular cortex: functional anatomy of OP2, its connectivity and the effect of vestibular disease.

Area OP2 in the posterior peri-sylvian cortex has been proposed to be the core human vestibular cortex. We investigated the functional anatomy of OP2 and adjacent areas (OP2+) using spatially constrained independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data from the Human Connectome Project. Ten ICA-derived subregions were identified. OP2+ responses to vestibular and visual motion were analyzed in 17 controls and 17 right-sided vestibular neuritis patients who had previously undergone caloric and optokinetic stimulation during fMRI. In controls, a posterior part of right OP2+ showed: (i) direction-selective responses to visual motion and (ii) activation during caloric stimulation that correlated positively with perceived self-motion, and negatively with visual dependence and peak slow-phase nystagmus velocity. Patients showed abnormal OP2+ activity, with an absence of visual or caloric activation of the healthy ear and no correlations with vertigo or visual dependence-despite normal slow-phase nystagmus responses to caloric stimulation. Activity in a lateral part of right OP2+ correlated with chronic visually induced dizziness in patients. In summary, distinct functional subregions of right OP2+ show strong connectivity to other vestibular areas and a profile of caloric and visual responses, suggesting a central role for vestibular function in health and disease.

Towards an explanation for 'unexplained' dizziness in older people.

BACKGROUND: Subjective unsteadiness or dizziness, usually without increase in body sway, is common in older people. The absence of mechanistic understanding of such symptoms renders clinical management difficult. Here, we explore the mechanisms behind such idiopathic dizziness (ID), focusing on postural control abnormalities. METHODS: Thirty patients with ID and 30 age-matched controls stood on a moving platform. Platform oscillations were randomly delivered at different velocities (from 0 to 0.2 m/s). Markers of postural control, including objective sway (trunk sway path, recorded via a sensor attached to vertebrae C7), stepping responses, subjective instability and anxiety ratings were obtained. MRI scans were available for correlations with levels of cerebral small vessel disease in 28 patients and 24 controls. RESULTS: We observed a significant relationship between objective and subjective instability in all groups. The slope of this fit was significantly steeper for patients than controls, indicating greater perceived instability for the same body sway. Stepwise linear regression showed that the slopes of this objective-subjective instability relationship were best explained by concerns about falling (Falls Efficacy Scale-International), clinical physical functioning (Short Physical Performance Battery) and, to some degree, by neuroimaging markers of cerebral small vessel disease. In addition, patients had a reduced stepping threshold, suggesting an overly cautious postural response. CONCLUSION: The distorted perception of instability and subtle impairments in balance control, including abnormal and overly cautious stepping responses, underlies the emergence of ID. It appears to relate to changes in postural performance, psychological functioning and disruption of postural brain networks associated with cerebral small vessel disease.

Vestibulo-spatial navigation: pathways and sense of direction.

Aims of the present article are: 1) assessing vestibular contribution to spatial navigation, 2) exploring how age, global positioning systems (GPS) use, and vestibular navigation contribute to subjective sense of direction (SOD), 3) evaluating vestibular navigation in patients with lesions of the vestibular-cerebellum (patients with downbeat nystagmus, DBN) that could inform on the signals carried by vestibulo-cerebellar-cortical pathways. We applied two navigation tasks on a rotating chair in the dark: return-to-start (RTS), where subjects drive the chair back to the origin after discrete angular displacement stimuli (path reversal), and complete-the-circle (CTC) where subjects drive the chair on, all the way round to origin (path completion). We examined 24 normal controls (20-83 yr), five patients with DBN (62-77 yr) and, as proof of principle, two patients with early dementia (84 and 76 yr). We found a relationship between SOD, assessed by Santa Barbara Sense of Direction Scale, and subject's age (positive), GPS use (negative), and CTC-vestibular-navigation-task (positive). Age-related decline in vestibular navigation was observed with the RTS task but not with the complex CTC task. Vestibular navigation was normal in patients with vestibulo-cerebellar dysfunction but abnormal, particularly CTC, in the demented patients. We conclude that vestibular navigation skills contribute to the build-up of our SOD. Unexpectedly, perceived SOD in the elderly is not inferior, possibly explained by increased GPS use by the young. Preserved vestibular navigation in cerebellar patients suggests that ascending vestibular-cerebellar projections carry velocity (not position) signals. The abnormalities in the cognitively impaired patients suggest that their vestibulo-spatial navigation is disrupted.NEW & NOTEWORTHY Our subjective sense-of-direction is influenced by how good we are at spatial navigation using vestibular cues. Global positioning systems (GPS) may inhibit sense of direction. Increased use of GPS by the young may explain why the elderly's sense of direction is not worse than the young's. Patients with vestibulo-cerebellar dysfunction (downbeat nystagmus syndrome) display normal vestibular navigation, suggesting that ascending vestibulo-cerebellar-cortical pathways carry velocity rather than position signals. Pilot data indicate that dementia disrupts vestibular navigation.

Electroencephalographic response to transient adaptation of vestibular perception.

When given a series of sinusoidal oscillations in which the two hemicycles have equal amplitude but asymmetric velocity, healthy subjects lose perception of the slower hemicycle (SHC), reporting a drift towards the faster hemicycle (FHC). This response is not reflected in the vestibular-ocular reflex, suggesting that the adaptation is of higher order. This study aimed to define EEG correlates of this adaptive response. Twenty-five subjects underwent a series of symmetric or asymmetric oscillations and reported their perceived head orientation at the end using landmarks in the testing room; this was converted into total position error (TPE). Thirty-two channel EEG was recorded before, during and after adaptation. Spectral power and coherence were calculated for the alpha, beta, delta and theta frequency bands. Linear mixed models were used to determine a region-by-condition effect of the adaptation. TPE was significantly greater in the asymmetric condition and reported error was always in the direction of the FHC. Regardless of condition, alpha desynchronised in response to stimulation, then rebounded back toward baseline values. This pattern was accelerated and attenuated in the prefrontal and occipital regions, respectively, in the asymmetric condition. Functional connectivity networks were identified in the beta and delta frequency bands; these networks, primarily comprising frontoparietal connections, were more coherent during asymmetric stimulation. These findings suggest that the temporary vestibulo-perceptual 'neglect' induced by asymmetric vestibular stimulation may be mediated by alpha rhythms and frontoparietal attentional networks. The results presented further our understanding of brain rhythms and cortical networks involved in vestibular perception and adaptation. KEY POINTS: Whole-body asymmetric sinusoidal oscillations, which consist of hemicycles with equal amplitude but differing velocities, can induce transient 'neglect' of the slower hemicycle in the vestibular perception of healthy subjects. In this study, we aimed to elucidate EEG correlates of this 'neglect', thereby identifying a cortical role in vestibular perception and adaptation. We identified a desynchronisation-resynchronisation response in the alpha frequency band (8-14 Hz) that was accelerated in the prefrontal region and attenuated in the occipital region when exposed to asymmetric, as compared to symmetric, rotations. We additionally identified functional connectivity networks in the beta (14-30 Hz) and delta (1-4 Hz) frequency bands consisting primarily of frontoparietal connections. These results suggest a prominent role of alpha rhythms and frontoparietal attentional networks in vestibular perception and adaptation.

RFC1 expansions are a common cause of idiopathic sensory neuropathy.

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies.

Vestibulo-perceptual influences upon the vestibulo-spinal reflex.

The vestibular system facilitates gaze and postural stability via the vestibulo-ocular (VOR) and vestibulo-spinal reflexes, respectively. Cortical and perceptual mechanisms can modulate long-duration VOR responses, but little is known about whether high-order neural phenomena can modulate short-latency vestibulo-spinal responses. Here, we investigate this by assessing click-evoked cervical vestibular myogenic-evoked potentials (VEMPS) during visual roll motion that elicited an illusionary sensation of self-motion (i.e. vection). We observed that during vection, the amplitude of the VEMPs was enhanced when compared to baseline measures. This modulation in VEMP amplitude was positively correlated with the subjective reports of vection strength. That is, those subjects reporting greater subjective vection scores exhibited a greater increase in VEMP amplitude. Control experiments showed that simple arousal (cold-induced discomfort) also increased VEMP amplitude but that, unlike vection, it did not modulate VEMP amplitude linearly. In agreement, small-field visual roll motion that did not induce vection failed to increase VEMP amplitude. Taken together, our results demonstrate that vection can modify the response of vestibulo-collic reflexes. Even short-latency brainstem vestibulo-spinal reflexes are influenced by high-order mechanisms, illustrating the functional importance of perceptual mechanisms in human postural control. As VEMPs are inhibitory responses, we argue that the findings may represent a mechanism whereby high-order CNS mechanisms reduce activity levels in vestibulo-collic reflexes, necessary for instance when voluntary head movements need to be performed.

Dissociated motor learning and de-adaptation in patients with functional gait disorders.

Walking onto a stationary platform that had been previously experienced as moving generates a locomotor after-effect-the so-called 'broken escalator' phenomenon. The motor responses that occur during locomotor after-effects have been mapped theoretically using a hierarchal Bayesian model of brain function that takes into account current sensory information that is weighted according to prior contextually-relevant experiences; these in turn inform automatic motor responses. Here, we use the broken escalator phenomenon to explore motor learning in patients with functional gait disorders and probe whether abnormal postural mechanisms override ascending sensory information and conscious intention, leading to maladaptive and disabling gait abnormalities. Fourteen patients with functional gait disorders and 17 healthy control subjects walked onto a stationary sled ('Before' condition, five trials), then onto a moving sled ('Moving' condition, 10 trials) and then again onto the stationary sled ('After' condition, five trials). Subjects were warned of the change in conditions. Kinematic gait measures (trunk displacement, step timing, gait velocity), EMG responses, and subjective measures of state anxiety/instability were recorded per trial. Patients had slower gait velocities in the Before trials (P < 0.05) but were able to increase this to accommodate the moving sled, with similar learning curves to control subjects (P = 0.87). Although trunk and gait velocity locomotor after-effects were present in both groups, there was a persistence of the locomotor after-effect only in patients (P < 0.05). We observed an increase in gait velocity during After trials towards normal values in the patient group. Instability and state anxiety were greater in patients than controls (P < 0.05) only during explicit phases (Before/After) of the task. Mean 'final' gait termination EMG activity (right gastrocnemius) was greater in the patient group than controls. Despite a dysfunctional locomotor system, patients show normal adaptive learning. The process of de-adaptation, however, is prolonged in patients indicating a tendency to perpetuate learned motor programmes. The trend to normalization of gait velocity following a period of implicit motor learning has implications for gait rehabilitation potential in patients with functional gait disorders and related disorders (e.g. fear of falling).

Pathophysiological dissociation of the interaction between time pressure and trait anxiety during spatial orientation judgments.

Spatial orientation is achieved by integrating visual, vestibular and proprioceptive cues. Individuals that rely strongly upon visual cues to facilitate spatial orientation are termed visually dependent. Heightened visual reliance commonly occurs in patients following vestibular dysfunction and can influence clinical outcome. Additionally, psychological factors, including anxiety, are associated with poorer clinical outcome following vestibular dysfunction. Given that visual dependency measures are affected by psychological and contextual influences, such as time pressure, we investigated the interaction between time pressure and anxiety upon visual dependency in healthy controls and vestibular migraine patients. Visual dependency was assessed using a "Rod and Disk" task at baseline and under time pressure (3 s to complete the task). Non-situational (trait) and situational (state) anxiety levels were quantified using the Spielberg State-Trait Anxiety Inventory. We calculated the change in visual dependency (VD) [∆VD = VDtime pressure  - VDbaseline ] and correlated it with participants' trait anxiety scores. We observed a significant negative correlation between trait anxiety and the change in VD (R2  = .393, p < .001) in healthy controls and a positive correlation in dizzy patients (R2  = .317, p < .001). That is, healthy individuals that were more anxious became less visually dependent under time pressure (i.e., more accurate), whereas less anxious individuals became more visually dependent. The reverse was observed in vestibular migraine patients. Our results illustrate that anxiety can differentially modulate task performance during spatial orientation judgements under time pressure in healthy individuals and dizzy patients. These findings have potential implications for individualised patient rehabilitation therapies.

Abnormal visuo-vestibular interactions in vestibular migraine: a cross sectional study.

Vestibular migraine is among the commonest causes of episodic vertigo. Chronically, patients with vestibular migraine develop abnormal responsiveness to both vestibular and visual stimuli characterized 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 been previously shown to modulate visual cortical excitability in both healthy individuals and avestibular patients, could disrupt vestibular ocular reflex 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.

Large gaze shift generation while standing: the role of the vestibular system.

The functional significance of vestibular information for the generation of gaze shifts is controversial and less well established than the vestibular contribution to gaze stability. In this study, we asked seven bilaterally avestibular patients to execute voluntary, whole body pivot turns to visual targets up to 180° while standing. In these conditions, not only are the demands imposed on gaze transfer mechanisms more challenging, but also neck proprioceptive input represents an inadequate source of head-in-space motion information. Patients' body segment was slower and jerky. In the absence of visual feedback, gaze advanced in small steps, closely resembling normal multiple-step gaze-shift patterns, but as a consequence of the slow head motion, target acquisition was delayed. In ~25% of trials, however, patients moved faster but the velocity of prematurely emerging slow-phase compensatory eye movements remained lower than head-in-space velocity due to vestibuloocular failure. During these trials, therefore, gaze advanced toward the target without interruption but, again, taking longer than when normal controls use single-step gaze transfers. That is, even when patients attempted faster gaze shifts, exposing themselves to gaze instability, they acquired distant targets significantly later than controls. Thus, while patients are upright, loss of vestibular information disrupts not only gaze stability but also gaze transfers. The slow and ataxic head and trunk movements introduce significant foveation delays. These deficits explain patients' symptoms during upright activities and show, for the first time, the clinical significance of losing the so-called "anticompensatory" (gaze shifting) function of the vestibuloocular reflex.NEW & NOTEWORTHY Previous studies in sitting avestibular patients concluded that gaze transfers are not substantially compromised. Still, clinicians know that patients are impeded (e.g., looking side to side before crossing a road). We show that during large gaze transfers while standing, vestibularly derived head velocity signals are critical for the mechanisms governing reorientation to distant targets and multisegmental coordination. Our findings go beyond the traditional role of the vestibular system in gaze stability, extending it to gaze transfers, as well.

Long-term clinical outcome in vestibular neuritis.

PURPOSE OF REVIEW: To review recent work on clinical and imaging aspects of vestibular neuritis (or acute vestibular syndrome), in particular with a view to identifying factors predicting long-term clinical outcome. RECENT FINDINGS: Evidence for a role of inflammation in the vestibular nerve, and the presence of Gadolinium enhancement acutely in vestibular neuritis, is accruing. Visual dependence, anxiety and somatization traits predict the development of chronic dizziness after acute vestibular neuritis. Adaptation to asymmetric rotation is impaired in vestibular neuritis and this may indicate insufficient central compensation in chronic dizzy patients. Corticosteroids appear ineffective at improving long-term clinical outcome. Functional imaging changes during the central compensation period lead to structural brain changes; both processes correlate with clinical recovery. SUMMARY: Vestibular neuritis appears to be the result of postviral neuroinflammation of the vestibular nerve. However, long-term prognosis is not dependent on the magnitude of the peripheral residual damage (as measured with caloric and video head-impulse test). Instead, a combination of visuovestibular psychophysical factors (visual dependence), psychological traits and dysfunctional vestibular perception are relevant. Several functional and structural neuroimaging changes develop after vestibular neuritis, which reflect and underlie the aforementioned psychophysiological and psychological features.

Viewing Target Distance Influences the Vestibulo-Ocular Reflex Gain when Assessed Using the Video Head Impulse Test.

Gaze stabilization during head movements is provided by the vestibulo-ocular reflex (VOR). Clinical assessment of this reflex is performed using the video Head Impulse Test (vHIT). To date, the influence of different fixation distances on VOR gain using the vHIT has not been explored. We assessed the effect of target proximity on the horizontal VOR using the vHIT. Firstly, we assessed the VOR gain in 18 healthy subjects with 5 viewing target distances (150, 40, 30, 20, and 10 cm). The gain increased significantly as the viewing target distance decreased. A second experiment on 10 subjects was performed in darkness whilst the subjects were imagining targets at different distances. There were significant inverse relationships between gain and distance for both the real and the imaginary targets. There was a statistically significant difference between light and dark gains for the 20- and 40-cm distances, but not for the 150-cm distance. Theoretical VOR gains for different target distances were calculated and compared with those found in light and darkness. The increase in gain observed for near targets was lower than predicted by geometrical calculations, implying a physiological ceiling effect on the VOR. The VOR gain in the dark, as assessed with the vHIT, demonstrates an enhancement associated with a reduced target distance.

Differential effect of visual motion adaption upon visual cortical excitability.

The objectives of this study were 1) to probe the effects of visual motion adaptation on early visual and V5/MT cortical excitability and 2) to investigate whether changes in cortical excitability following visual motion adaptation are related to the degree of visual dependency, i.e., an overreliance on visual cues compared with vestibular or proprioceptive cues. Participants were exposed to a roll motion visual stimulus before, during, and after visual motion adaptation. At these stages, 20 transcranial magnetic stimulation (TMS) pulses at phosphene threshold values were applied over early visual and V5/MT cortical areas from which the probability of eliciting a phosphene was calculated. Before and after adaptation, participants aligned the subjective visual vertical in front of the roll motion stimulus as a marker of visual dependency. During adaptation, early visual cortex excitability decreased whereas V5/MT excitability increased. After adaptation, both early visual and V5/MT excitability were increased. The roll motion-induced tilt of the subjective visual vertical (visual dependence) was not influenced by visual motion adaptation and did not correlate with phosphene threshold or visual cortex excitability. We conclude that early visual and V5/MT cortical excitability is differentially affected by visual motion adaptation. Furthermore, excitability in the early or late visual cortex is not associated with an increase in visual reliance during spatial orientation. Our findings complement earlier studies that have probed visual cortical excitability following motion adaptation and highlight the differential role of the early visual cortex and V5/MT in visual motion processing.NEW & NOTEWORTHY We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individual's visual dependency.

Influence of biases in numerical magnitude allocation on human prosocial decision making.

Over the past decade neuroscientific research has attempted to probe the neurobiological underpinnings of human prosocial decision making. Such research has almost ubiquitously employed tasks such as the dictator game or similar variations (i.e., ultimatum game). Considering the explicit numerical nature of such tasks, it is surprising that the influence of numerical cognition on decision making during task performance remains unknown. While performing these tasks, participants typically tend to anchor on a 50:50 split that necessitates an explicit numerical judgement (i.e., number-pair bisection). Accordingly, we hypothesize that the decision-making process during the dictator game recruits overlapping cognitive processes to those known to be engaged during number-pair bisection. We observed that biases in numerical magnitude allocation correlated with the formulation of decisions during the dictator game. That is, intrinsic biases toward smaller numerical magnitudes were associated with the formulation of less favorable decisions, whereas biases toward larger magnitudes were associated with more favorable choices. We proceeded to corroborate this relationship by subliminally and systematically inducing biases in numerical magnitude toward either higher or lower numbers using a visuo-vestibular stimulation paradigm. Such subliminal alterations in numerical magnitude allocation led to proportional and corresponding changes to an individual's decision making during the dictator game. Critically, no relationship was observed between neither intrinsic nor induced biases in numerical magnitude on decision making when assessed using a nonnumerical-based prosocial questionnaire. Our findings demonstrate numerical influences on decisions formulated during the dictator game and highlight the necessity to control for confounds associated with numerical cognition in human decision-making paradigms.NEW & NOTEWORTHY We demonstrate that intrinsic biases in numerical magnitude can directly predict the amount of money donated by an individual to an anonymous stranger during the dictator game. Furthermore, subliminally inducing perceptual biases in numerical-magnitude allocation can actively drive prosocial choices in the corresponding direction. Our findings provide evidence for numerical influences on decision making during performance of the dictator game. Accordingly, without the implementation of an adequate control for numerical influences, the dictator game and other tasks with an inherent numerical component (i.e., ultimatum game) should be employed with caution in the assessment of human behavior.

Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière's disease: a randomised, double-blind, comparative effectiveness trial.

BACKGROUND: Ménière's disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin, the standard treatment for refractory Ménière's disease, reduces vertigo, but damages vestibular function and can worsen hearing. We aimed to assess whether intratympanic administration of the corticosteroid methylprednisolone reduces vertigo compared with gentamicin. METHODS: In this double-blind comparative effectiveness trial, patients aged 18-70 years with refractory unilateral Ménière's disease were enrolled at Charing Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK). Patients were randomly assigned (1:1) by a block design to two intratympanic methylprednisolone (62·5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks apart, and were followed up for 2 years. All investigators and patients were masked to treatment allocation. The primary outcome was vertigo frequency over the final 6 months (18-24 months after injection) compared with the 6 months before the first injection. Analyses were done in the intention-to-treat population, and then per protocol. This trial is registered with ClinicalTrials.gov, number NCT00802529. FINDINGS: Between June 19, 2009, and April 15, 2013, 256 patients with Ménière's disease were screened, 60 of whom were enrolled and randomly assigned: 30 to gentamicin and 30 to methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the mean number of vertigo attacks in the final 6 months compared with the 6 months before the first injection (primary outcome) decreased from 19·9 (SD 16·7) to 2·5 (5·8) in the gentamicin group (87% reduction) and from 16·4 (12·5) to 1·6 (3·4) in the methylprednisolone group (90% reduction; mean difference -0·9, 95% CI -3·4 to 1·6). Patients whose vertigo did not improve after injection (ie, non-responders) after being assessed by an unmasked clinician were eligible for additional injections given by a masked clinician (eight patients in the gentamicin group vs 15 in the methylprednisolone group). Two non-responders switched from methylprednisolone to gentamicin. Both drugs were well tolerated with no safety concerns. Six patients reported one adverse event each: three in the gentamicin group and three in the methylprednisolone group. The most common adverse event was minor ear infections, which was experienced by one patient in the gentamicin group and two in the methylprednisolone group. INTERPRETATION: Methylprednisolone injections are a non-ablative, effective treatment for refractory Ménière's disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances. FUNDING: Ménière's Society and National Institute for Health Research Imperial Biomedical Research Centre.

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.

Bidirectional Modulation of Numerical Magnitude.

Numerical cognition is critical for modern life; however, the precise neural mechanisms underpinning numerical magnitude allocation in humans remain obscure. Based upon previous reports demonstrating the close behavioral and neuro-anatomical relationship between number allocation and spatial attention, we hypothesized that these systems would be subject to similar control mechanisms, namely dynamic interhemispheric competition. We employed a physiological paradigm, combining visual and vestibular stimulation, to induce interhemispheric conflict and subsequent unihemispheric inhibition, as confirmed by transcranial direct current stimulation (tDCS). This allowed us to demonstrate the first systematic bidirectional modulation of numerical magnitude toward either higher or lower numbers, independently of either eye movements or spatial attention mediated biases. We incorporated both our findings and those from the most widely accepted theoretical framework for numerical cognition to present a novel unifying computational model that describes how numerical magnitude allocation is subject to dynamic interhemispheric competition. That is, numerical allocation is continually updated in a contextual manner based upon relative magnitude, with the right hemisphere responsible for smaller magnitudes and the left hemisphere for larger magnitudes.