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The intraparietal sulcus within the dorsal right posterior parietal cortex is associated with spatial orientation and attention in relation to egocentric reference frames, such as left or right hemifield. It remains unclear whether it plays a causal role in the human in the roll plane (i.e. when visual stimuli are tilted clockwise or anticlockwise) which this is an important aspect of egocentric visual processing with clinical relevance in vestibular disorders. The subjective visual vertical (SVV) task measures the deviation between an individual's subjective vertical perception and the veridical vertical, involves the integration of visual, and vestibular information, and relies on a distributed network of multisensory regions that shows right lateralization and inter-areal inhibition. This study used combined TMS-EEG to investigate the role of the human dorsal parietal cortex in verticality perception using the SVV task in darkness. Participants were sorted according to their baseline bias at this task i.e. those with either a slight counterclockwise versus clockwise bias when judging a line to be truly vertical. Right parietal TMS facilitated verticality perception, reducing the difference between groups. ERPs suggested that the behavioral TMS effect occurred through normalizing individual SVV biases, evident frontally and late in the trial, and which was abolished after right parietal TMS. Effects were site and task specific, shown with a homologous left hemisphere control, and a landmark task performed on the same stimuli. These results support a right lateralization of visual-vestibular cognition and a distinct representation of the roll plane for egocentric processing in dorsal parietal cortex.

An acute unilateral vestibulopathy leads to symptoms of vestibular tone imbalance, which gradually decrease over days to weeks due to central vestibular compensation. Animal models of acute peripheral vestibular lesions are optimally suited to investigate the mechanisms underlying this lesion-induced adaptive neuroplasticity. Previous studies applied ex vivo histochemical techniques or local in vivo electrophysiological recordings mostly in the vestibular nucleus complex to delineate the mechanisms involved. Recently, the use of imaging methods, such as positron emission tomography (PET) or magnetic resonance imaging (MRI), in vestibular animal models have opened a complementary perspective by depicting whole-brain structure and network changes of neuronal activity over time and in correlation to behaviour. Here, we review recent multimodal imaging studies in vestibular animal models with a focus on PET-based measurements of glucose metabolism, glial activation and synaptic plasticity. [18F]-FDG-PET studies indicate dynamic alterations of regional glucose metabolism in brainstem-cerebellar, thalamic, cortical sensory and motor, as well as limbic areas starting early after unilateral labyrinthectomy (UL) in the rat. Sequential whole-brain analysis of the metabolic connectome during vestibular compensation shows a significant increase of connections mostly in the contralesional hemisphere after UL, which reaches a maximum at day 3 and thereby parallels the course of vestibular recovery. Glial activation in the ipsilesional vestibular nerve and nucleus peak between days 7 and 15 after UL. Synaptic density in brainstem-cerebellar circuits decreases until 8 weeks after UL, while it increases in frontal, motor and sensory cortical areas. We finally report how pharmacological compounds modulate the functional and structural plasticity mechanisms during vestibular compensation.

Current evidence points towards a vestibular cortex that involves a multisensory bilateral temporo-parietal-insular network with a handedness-dependent hemispheric lateralization. This study aimed to identify handedness-dependent organizational patterns of (lateralized and non-lateralized) functional subunits within the human vestibular cortex areas. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state functional MRI (fMRI). The data was analyzed in four major steps using a functional connectivity based parcellation (fCBP) approach: (1) independent component analysis (ICA) on a whole brain level to identify different resting state networks (RSN); (2) creation of a vestibular informed mask from four whole brain ICs that included reference coordinates of the vestibular network extracted from meta-analyses of vestibular neuroimaging experiments; (3) Re-ICA confined to the vestibular informed mask; (4) cross-correlation of the activated voxels within the vestibular subunits (parcels) to each other (P-to-P) and to the whole-brain RSN (P-to-RSN). This approach disclosed handedness-dependency, inter-hemispheric symmetry, the scale of connectedness to major whole brain RSN and the grade of spatial overlap of voxels within parcels (common/unique) as meaningful discriminatory organizational categories within the vestibular cortex areas. This network consists of multiple inter-hemisphere symmetric (not lateralized), well-connected (many RSN-assignments) multisensory areas (or hubs; e.g., superior temporal gyrus, temporo-parietal intersection) organized around an asymmetric (lateralized, "dominant") and functionally more specialized (few RSN-assignments) core region in the parieto-insular cortex. The latter is in the middle, posterior and inferior insula. In conclusion, the bilateral cortical vestibular network contains not only a handedness-dependent lateralized central region concentrated in the right hemisphere in right-handers and left hemisphere in left-handers, but also surrounding inter-hemisphere symmetric multisensory vestibular areas that seem to be functionally influenced by their neighboring sensory systems (e.g., temporo-parietal intersection by the visual system). One may speculate that the development of an asymmetrical organized vestibular subsystem reflects a more recent phylogenetic evolution of various multisensory vestibular functions. The right hemispheric dominance of spatial orientation and its disorders, spatial neglect and pusher syndrome, may serve as examples.

Multisensory convergence and sensorimotor integration are important aspects for the mediation of higher vestibular cognitive functions at the cortical level. In contrast to the integration of vestibulo-visual or vestibulo-tactile perception, much less is known about the neural mechanism that mediates the integration of vestibular-otolith (linear acceleration/translation/gravity detection) and auditory processing. Vestibular-otolith and auditory afferents can be simultaneously activated using loud sound pressure stimulation, which is routinely used for testing cervical and ocular vestibular evoked myogenic potentials (VEMPs) in clinical neurotological testing. Due to the simultaneous activation of afferents there is always an auditory confound problem in fMRI studies of the neural topology of these systems. Here, we demonstrate that the auditory confounding problem can be overcome in a novel way that does not require the assumption of simple subtraction and additionally allows detection of non-linear changes in the response due to vestibular-otolith interference. We used a parametric sound pressure stimulation design that took each subject's vestibular stimulation threshold into account and analyzed for changes in BOLD-response below and above vestibular-otolith threshold. This approach helped to investigate the functional neuroanatomy of sound-induced auditory and vestibular integration using functional magnetic resonance imaging (fMRI). Results revealed that auditory and vestibular convergence are contained in overlapping regions of the caudal part of the superior temporal gyrus (STG) and the posterior insula. In addition, there are regions that were responsive only to suprathreshold stimulations, suggesting vestibular (otolith) signal processing in these areas. Based on these parametric analyses, we suggest that the caudal part of the STG and posterior insula could contain areas of vestibular contribution to auditory processing, i.e., higher vestibular cortices that provide multisensory integration that is important for tasks such as spatial localization of sound.

Metabolic connectivity patterns on the basis of [18F]-FDG positron emission tomography (PET) are used to depict complex cerebral network alterations in different neurological disorders and therefore may have the potential to support diagnostic decisions. In this study, we established a novel statistical classification method taking advantage of differential time-dependent states of whole-brain metabolic connectivity following unilateral labyrinthectomy (UL) in the rat and explored its classification accuracy. The dataset consisted of repeated [18F]-FDG PET measurements at baseline and 1, 3, 7, and 15 days (= maximum of 5 classes) after UL with 17 rats per measurement day. Classification in different stages after UL was performed by determining connectivity patterns for the different classes by Pearson's correlation between uptake values in atlas-based segmented brain regions. Connections were fitted with a linear function, with which different thresholds on the correlation coefficient (r = [0.5, 0.85]) were investigated. Rats were classified by determining the congruence of their PET uptake pattern with the fitted connectivity patterns in the classes. Overall, the classification accuracy with this method was 84.3% for 3 classes, 75.0% for 4 classes, and 54.1% for 5 classes and outperformed random classification as well as machine learning classification on the same dataset. The optimal classification thresholds of the correlation coefficient and distance-to-fit were found to be |r| > 0.65 and d = 4 when using Siegel's slope estimator for fitting. This connectivity-based classification method can compete with machine learning classification and may have methodological advantages when applied to support PET-based diagnostic decisions in neurological network disorders (such as neurodegenerative syndromes).

Unilateral damage to the inner ear results in an acute vestibular syndrome, which is compensated within days to weeks due to adaptive cerebral plasticity. This process, called central vestibular compensation (VC), involves a wide range of functional and structural mechanisms at the cellular and network level. The short-term dynamics of whole-brain functional network recruitment and recalibration during VC has not been depicted in vivo. The purpose of this study was to investigate the interplay of separate and distinct brain regions and in vivo networks in the course of VC by sequential [18F]-FDG-PET-based statistical and graph theoretical analysis with the aim of revealing the metabolic connectome before and 1, 3, 7, and 15 days post unilateral labyrinthectomy (UL) in the rat. Temporal changes in metabolic brain connectivity were determined by Pearson's correlation (|r| > 0.5, p < 0.001) of regional cerebral glucose metabolism (rCGM) in 57 segmented brain regions. Metabolic connectivity analysis was compared to univariate voxel-wise statistical analysis of rCGM over time and to behavioral scores of static and dynamic sensorimotor recovery. Univariate statistical analysis revealed an ipsilesional relative rCGM decrease (compared to baseline) and a contralesional rCGM increase in vestibular and limbic networks and an increase in bilateral cerebellar and sensorimotor networks. Quantitative analysis of the metabolic connections showed a maximal increase from baseline to day 3 post UL (interhemispheric: 2-fold, ipsilesional: 3-fold, contralesional: 12-fold) and a gradual decline until day 15 post UL, which paralleled the dynamics of vestibular symptoms. In graph theoretical analysis, an increase in connectivity occurred especially within brain regions associated with brainstem-cerebellar and thalamocortical vestibular networks and cortical sensorimotor networks. At the symptom peak (day 3 post UL), brain networks were found to be organized in large ensembles of distinct and highly connected hubs of brain regions, which separated again with progressing VC. Thus, we found rapid changes in network organization at the subcortical and cortical level and in both hemispheres, which may indicate an initial functional substitution of vestibular loss and subsequent recalibration and reorganization of sensorimotor networks during VC.

In patients with left-sided lesions, anosognosia for hemiparesis (AHP) seems to be a rare phenomenon. It has been discussed whether this rareness might be due to an inevitable bias due to language dysfunction and whether the left hemisphere's role for our self-awareness of motor actions thus is underestimated. By applying functional magnetic resonance imaging (fMRI) we examined whether patients with AHP following a left hemisphere stroke show a regular, left-sided or a reversed, right-sided lateralization of language functions. Only the former observation would argue for an original role of the left hemisphere in self-awareness about limb function. In a consecutive series of 44 acute left-sided stroke patients, only one patient (=2%) was identified showing AHP. In this case, we could verify by using fMRI that lateralization of AHP and spatial neglect on the one hand and of language functions on the other hand were reversed. The present single case observation thus argues against an original role of the left hemisphere in self-awareness about limb function. We discuss the data in the context of previous observations in the literature.

The present study aimed to reveal the effects of age on the temporal profile of the positive blood-oxygen-level–dependent response (PBR) during low-velocity optokinetic nystagmus (OKN) in healthy subjects. We were specifically interested in comparing these effects with the effects of age on the PBR elicited by pure visual and motor tasks. Therefore, we conducted 2 additional control experiments: a checkerboard experiment (visual stimulation) and a finger-tapping (motor task) experiment. Whereas the oculomotor performance of the subjects remained unaltered, the temporal profile of the PBR changed significantly with increasing age in visual and oculomotor areas. None of the control experiments revealed significant age-related PBR changes. Thus, this study demonstrates that the PBR changes during OKN occur before any changes in the oculomotor performance can be detected. These effects of age are specific for the OKN task and probably reflect both changes in the neurovascular coupling and changes in the neural processing during OKN.

Aim Galvanic vestibular stimulation (GVS) allows for robust vestibular responses and is therefore the gold standard in neuroimaging studies focusing on the central vestibular system. Nevertheless, there are several confounding side-effects which hinder the delineation of pure vestibular responses. Besides stimulating vestibular hair cells and afferent fibers [1] , mastoidal GVS also evokes somatosensory, vagal and nociceptive responses. Furthermore, GVS induces reflectory head movements leading to motion artefacts. Aim of our fMRI study was to assess and control for the impact of these confounders by means of local anaesthesia, optimized head fixation, and a sham-GVS stimulation with different current intensities. Methods We examined 44 right-handed healthy subjects (21 F; mean age 28 years) in three sessions (interval length between session > 24 h) with different conditions: GVS with 3.5 mA with/without local anaesthesia, sham-GVS with 3.5 mA/1 mA, and GVS with/without head fixation (headfixation system: Pearltec, Switzerland). Structural and functional images were obtained in a clinical 3T scanner (Siemens Magnetom Verio) with a 32-channel head coil. The protocol included a GVS stimulation session consisting of a T2*-weighted EPI sequence (TR 2s, 31 ascending slices, 3 mm in-plane resolution, slice thickness 3.5 mm), a MPRAGE sequence, and a resting-state session. Data analysis was performed using SPM 12 (Version 6407 Wellcome Department of Imaging Neuroscience, UK) and the motion fingerprint toolbox (Wilke, Neuroimage 2012) after standard preprocessing using DARTEL-based normalization. Results were considered significant at FDR p 0.05 (corrected at cluster level). Results Pain perception during GVS decreased significantly after local anesthesia (NRS-11 reduction from 4.5 to 1.7, Wilcoxon signed-rank test, Z = −3.79, p = 0.00). GVS with lidocaine evoked responses in the vestibular network, predominantly in right OP2 and the medial cingulate cortex bilaterally, which were absent during sham stimulation. Without anesthesia, confluent activation cluster were found in anterior and posterior insula-opercular regions. Activation of the insula was also shown bilaterally during sham-GVS, with a predominant effect in area OP1 and area PF with a current intensity of 3.5 mA. Sham-GVS with 1 mA led to bilateral responses in area Fp1, the precentral gyrus and the left posterior cingulum. Motion finger print analysis in GVS with and without head fixation revealed head motion predominantly in the roll plane, leading to inter-slice motion artefacts in temporo-parietal-opercular regions. These artefacts were eliminated using a new head fixation system. Conclusion In this fMRI study, we evaluated and minimized the effects of several confounders in GVS. Head motion artefacts as well as nociceptive and somatosensory responses may hinder the localization of actual vestibular response patterns, particularly in the insula and parietal operculum. Our results highlight the importance of controlling for these side-effects and lead the way towards a precise definition of the human vestibular cortical network.

It is known that the functional response (e.g., nystagmus) to caloric vestibular stimulation is delayed and prolonged compared with the stimulus-response timing of other sensory systems. Imaging studies have used different models to predict cortical responses and to determine the areas of the brain that are involved. These studies have revealed a widespread network of vestibular brain regions. However, there is some disagreement regarding the brain areas involved, which may partly be caused by differences in the models used. This disagreement indicates the possible existence of multiple cortical components with different temporal characteristics that underlie cortical vestibular processing. However, data-driven methods have yet to be used to analyze the underlying hemodynamic components during and after vestibular stimulation. We performed functional magnetic resonance imaging (fMRI) on 12 healthy subjects during caloric stimulation and analyzed these data using a model-free analysis method (ICA). We found seven independent stimulus-induced components that outline a robust pattern of cortical activation and deactivation. These independent components demonstrated significant differences in their time courses. No single-modeled response function was able to cover the entire range of these independent components. The response functions determined in the present study should improve model-based studies investigating vestibular cortical processing.

Patients with vestibular vertigo syndromes often suffer from anxiety and depression, whereas patients with psychiatric disorders often experience subjective unsteadiness, dizziness, or vertigo. Thus, it has been hypothesized that the vestibular system may be interlinked with the emotion processing systems. The aim of the current study was to evaluate this hypothesis by correlating vestibular and psychiatric symptoms with the course of the disease over 1 year. This interdisciplinary, prospective, longitudinal study included a total of 68 patients with acute vestibular vertigo syndromes. Four subgroups of patients with benign paroxysmal positioning vertigo (BPPV, n=19), acute vestibular neuritis (VN, n=14), vestibular migraine (VM, n=27), or Meniere's disease (MD, n=8) were compared. All patients underwent neurological and neuro-otological examinations and filled out standardized self-report inventories including the Vertigo Symptom Scale (VSS), the Vertigo Handicap Questionnaire (VHQ) and the Symptom Checklist 90R (GSI, SCL-90R) at five different times (T0-T4) in the course of 1 year. VM patients experienced significantly more "vertigo and related symptoms" (VSS-VER), "somatic anxiety and autonomic arousal" (VSS-AA), and "vertigo induced handicap" (VHQ) than all other patients (P

The definition of neuropathic pain has recently been revised by an expert committee of the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) as "pain arising as direct consequence of a lesion or disease affecting the somatosensory system," and a grading system of "definite," "probable," and "possible" neuropathic pain has been introduced. This open case series of 5 outpatients (3 men, 2 women; mean age 48 +/- 12 years) demonstrates how the grading system can be applied, in combination with appropriate confirmatory testing, to diagnosis neuropathic conditions in clinical practice. The proposed grading system includes a dynamic algorithm that enhances the physician's ability to determine with a greater level of certainty whether a pain condition is neuropathic. Its clinical use should be further validated in prospective studies.

Background: Due to the lack of epidemiological data on the relation of dizziness and anxiety, we investigated the prevalence of dizziness and anxiety in a representative sample of the German population. We explored the consequences of comorbid anxiety for emotional distress, functional impairment, health care utilization, and health behavior in dizziness. Methods: By the end of 2006, we surveyed a total of 1287 persons between 14 and 90 years of age in their homes by trained interviewers with standardized self-rating questionnaires on anxiety (Patient Health Questionnaire, Generalized Anxiety Disorder Scale, Mini-Social Phobia Inventory) and dizziness (Vertigo Symptom Scale). The sample was representative for the German population in terms of age, sex, and education. Results: Symptoms of dizziness were reported by 15.8% of the participants. Of the participants with dizziness, 28.3% reported symptoms of at least one anxiety disorder (generalized anxiety, social phobia, panic). Persons with dizziness reported more somatic problems such as hypertension, migraine, diabetes, etc. Comorbid anxiety was associated with increased health care use and impairment. Conclusion: Dizziness is a highly prevalent symptom in the general population. A subgroup with comorbid anxiety is characterized by an increased subjective impairment and health care utilization due to their dizziness. Because treatment options for distinct neurotologic disorders are also known to reduce psychological symptoms, and in order to avoid unnecessary medical treatment, early neurologic and psychiatric/psychotherapeutic referral may be indicated.

Earlier functional imaging studies on the processing of vestibular information mainly focused on cortical activations due to stimulation of the horizontal semicircular canals in right-handers. Two factors were found to determine its processing in the temporo-parietal cortex: a dominance of the non-dominant hemisphere and an ipsilaterality of the neural pathways. In an investigation of the role of these factors in the vestibular otoliths, we used vestibular evoked myogenic potentials (VEMPs) in a fMRI study of monaural saccular-otolith stimulation. Our aim was to (1) analyze the hemispheric dominance for saccular-otolith information in healthy left-handers, (2) determine if there is a predominance of the ipsilateral saccular-otolith projection, and (3) evaluate the impact of both factors on the temporo-parieto-insular activation pattern. A block design with three stimulation and rest conditions was applied: (1) 102 dB-VEMP stimulation; (2) 65 dB-control-acoustic stimulation, (3) 102 dB-white-noise-control stimulation. After subtraction of acoustic side effects, bilateral activations were found in the posterior insula, the superior/middle/transverse temporal gyri, and the inferior parietal lobule. The distribution of the saccular-otolith activations was influenced by the two factors but with topographic disparity: whereas the inferior parts of the temporo-parietal cortex were mainly influenced by the ipsilaterality of the pathways, the upper parts reflected the dominance of the non-dominant hemisphere. This is in contrast to the processing of acoustic stimulation, which showed a predominance of the contralateral pathways. Our study proves the importance of the hemispheric preponderance also in left-handers, which is of relevance in the superior parts of the insula gyrus V, the inferior parietal lobule, and the superior temporal gyri.

The topodiagnostic implications of hemiataxia following lesions of the human brainstem are only incompletely understood. We performed a voxel-based statistical analysis of lesions documented on standardised MRI in 49 prospectively recruited patients with acute hemiataxia due to isolated unilateral brainstem infarction. For statistical analysis individual MRI lesions were normalised and imported in a three-dimensional voxel-based anatomical model of the human brainstem. Statistical analysis revealed hemiataxia to be associated with lesions of three distinct brainstem areas. The strongest correlation referred to ipsilateral rostral and dorsolateral medullary infarcts affecting the inferior cerebellar peduncle, and the dorsal and ventral spinocerebellar tracts. Secondly, lesions of the ventral pontine base resulted in contralateral limb ataxia, especially when ataxia was accompanied by motor hemiparesis. In patients with bilateral hemiataxia, lesions were located in a paramedian region between the upper pons and lower midbrain, involving the decussation of dentato-rubro-thalamic tracts. We conclude that ataxia following brainstem infarction may reflect three different pathophysiological mechanisms. (1) Ipsilateral hemiataxia following dorsolateral medullary infarctions results from a lesion of the dorsal spinocerebellar tract and the inferior cerebellar peduncle conveying afferent information from the ipsilateral arm and leg. (2) Pontine lesions cause contralateral and not bilateral ataxia presumably due to major damage to the descending corticopontine projections and pontine base nuclei, while already crossed pontocerebellar fibres are not completely interrupted. (3) Finally, bilateral ataxia probably reflects a lesion of cerebellar outflow on a central, rostral pontomesencephalic level.

Short tone bursts trigger a vestibular evoked myogenic potential (VEMP), an inhibitory potential which reflects a component of the vestibulocollic reflex (VCR). These potentials arise as a result of activation of the sacculus and are expressed through the vestibulo-collic reflex (VCR). Up to now, the ascending projections of the sacculus are unknown in humans, only the representation of the semicircular canals or the entire vestibular nerve has been demonstrated. The aim of this study was to determine whether a sacculus stimulus that evoked VEMPs could activate vestibular cortical areas in fMRI. To determine this, we studied the differential effects of unilateral VEMP stimulation in 21 healthy right-handers in a clinical 1.5 T scanner while wearing piezo electric headphones. A unilateral VEMP stimulus and two auditory control stimuli were given in randomized order over the stimulated ear. A random effects statistical analysis was done with SPM2 (p0.05, corrected). After exclusion of the auditory effects, the major findings were as follows: (i) significant activations were located in the multisensory cortical vestibular network within both hemispheres, including the posterior insular cortex, the middle and superior temporal gyri, and the inferior parietal cortex. (ii) The activation pattern was elicited bilaterally with a predominance of the right hemisphere in right-handers. (iii) Saccular vestibular projection was predominantly ipsilateral, whereas (iv) pure acoustic stimuli were processed with a predominance of the respective contralateral and mainly in the left hemisphere. This is the first demonstration by means of fMRI of the cortical representation of the saccular input at cortical level. The activation pattern is similar to that known from the stimulation of the entire vestibular nerve or the horizontal semicircular canal. Our data give evidence of a task-dependent separation of the processing within the vestibular otolith and the auditory systems in the two hemispheres.

Jugular venous valve insufficiency is a contributing factor to different pathologic conditions. For assessment of insufficiency, two ultrasound techniques have been developed, that are based on very different methodology (direct Doppler assessment versus air contrast ultrasound venography [ACUV]). This study was conducted to compare these two methods to improve comparability of existing studies and diagnostic accuracy in future studies. The function of 40 valves was determined in 20 individuals during a Valsalva maneuver. For direct Doppler assessment, valvular competence was assessed on basis of Doppler recordings, following recently established criteria. Valvular insufficiency in ACUV was diagnosed when reflux of an air-based echo contrast agent through the valve could be detected. With both methods, evaluation of 39 valves was accomplished (one exclusion due to hypoplasia of the corresponding vein). Both methods showed very high agreement in detection rates. All 18 valves being classified as insufficient by Doppler criteria were also insufficient in ACUV. Of 21 valves classified as competent (Doppler), one valve was rated as insufficient in ACUV due to discrete reflux of microbubbles. However, ACUV was inaccurate in evaluation of the left internal jugular vein after injection of the contrast agent into the right cubital vein. High detection rates could only be achieved when this was taken into account. This study shows that detection rates of internal jugular valve insufficiency are very similar with both methods. However, this high agreement required modification of the established protocol of ACUV. (E-mail: max.nedelmann@neuro.med.uni-giessen.de )

During fixation of a stationary, dim light-emitting diode (LED) in complete darkness, a subtle, apparent motion is perceived which is called autokinesis. This autokinetic illusion increases with increasing fixation time. Eleven healthy subjects were examined by fMRI while fixating an LED in darkness for 35 s. BOLD signal changes of the first and the second half of the fixation period were compared. While the stimulus was the same for both periods, perception differed in that autokinesis was more pronounced in the second half. This second half of the period was associated with bilateral activations in the motion-sensitive middle occipito-temporal area known as MT/V5. Our finding suggests that area MT/V5 is involved in the mediation of autokinesis.

Nearly half the patients who are in specialized otoneurologic units exhibit psychiatric disorders. The disorders are most significant in patients who have the chief symptoms of dizziness, complex forms of tinnitus, or sudden and relapsing sensorineural hearing loss. If not properly diagnosed, these disorders can lead to improper treatment, particularly when the illness is a somatoform otoneurologic disorder. Patients who have comorbid symptoms, such as reactive anxiety or depressive disorders, may experience difficulties in coping with the illness. In many instances, reactive psychologic disorders can lead to severe impairment of daily life and work activities.

The patterns of associated brain activations during eyes-open and eyes-closed states in complete darkness considerably differ in fMRI. An "interoceptive" state with the eyes closed is characterized by visual cortex activation, while an "exteroceptive" state with the eyes open is characterized by ocular motor system activity. The impact of the chosen rest condition (eyes open or eyes closed in complete darkness) on the pattern of brain activations during visual stimulation was evaluated in 14 healthy volunteers. During fixation or dim light room illumination, the activation of the visual cortex was larger with the eyes-open rest condition than with the eyes-closed rest condition; however, activation of the lateral geniculate nucleus was smaller. Activations that can be attributed to ocular motor structures, such as the prefrontal cortex, parietal and frontal eye fields, cerebellar vermis, the thalamus, and basal ganglia were larger with the eyes-closed rest condition than with the eyes-open rest condition. BOLD signal decreases of cortical areas that represent visual, somatosensory, auditory, and vestibular functions were seen in the comparison fixation of light emitting diode (LED) minus eyes closed. Thus, the choice of rest condition (either eyes closed or eyes open) is critical for stimulus-induced brain activation patterns. Activity of the ocular motor system as well as deactivation of sensory cortical areas may go undetected with eyes open as rest condition.

Background and aim Characterisation of the spatial orientation and locomotion behaviour after bilateral vestibular labyrinthectomy in the rat. Methods Ten Sprague-Dawley rats underwent a bilateral labyrinthectomy (BL) by transtympanic injection of bupivacaine and arsenilate, 10 rats received a bilateral middle-ear injection of saline (sham) as a control group. Behavioural testing was performed 1 day before and at days 1, 2, 3, 7, 15, 30 and 60 after BL/sham injection as follows: (1) analysis of spatial exploration behaviour in a square open field by the Noldus EthoVision System; (2) quantitative analysis of locomotion pattern by the Noldus CatWalk System. Results At all time points, rats of the sham group showed a strategically distributed exploration pattern with a preferred movement along the lateral edges and a preferred position in the corners of the open field. The exploration behaviour was guided by head movements in the lateral direction. In contrast, rats of the BL group presented with a omnidirectional exploration strategy and stayed in the central parts of the open field significantly longer. This exploration pattern did not change over time. Lateral head and body turns were reduced relative to controls. Mean velocity during exploration in the open field was significantly higher in the BL than in the sham group until day 60, whereas mean velocity during CatWalk measurement adapted between groups after day 15 post BL/sham injection. Conclusions A bilateral vestibular lesion induces a persistent deficit in spatial exploration behaviour. The pathophysiological basis seems to be a disturbance of head direction cells in the hippocampal formation due to the lack of vestibular input.

Background Functional imaging studies on the central vestibular system by fMRI and H 2 15 O-PET in healthy volunteers revealed similarities and differences in cortical activation patterns ( Bense, 2001 , Dietrich, 2003 , Stephan, 2005 , Stephan, 2009 , Becker-Bense, 2014 ). These are ascribed to different experimental procedures and techniques. Whereas PET maps cerebral blood flow, fMRI measures changes of blood oxygenation via magnetic susceptibility changes.Galvanic vestibular stimulation (GVS) is applicable inside PET and MRI; it induces a perception of apparent self-motion mainly at onset ( Stephan, 2009 ). Aim of the current study was to design a protocol for simultaneous PET-MRI of the vestibular system in order to compare the activation patterns between the two methods providing additional information for a deeper insight into the different mechanisms and improve the interpretation of the data. Methods Six simultaneous PET-MRI scans were acquired in a hybrid scanner in nine healthy volunteers. During the stimulation scans AC-GVS was applied at 1 Hz ( Stephan, 2005 ) with eyes closed ( Fig. 1 ). FMRI EPI sequences were measured over 260 s. Dynamic PET acquisition started with injection of 750 MBq H 2 15 O in a semibolus technique simultaneously with fMRI. Statistical direct comparison of PET and fMRI data were performed (paired t-test, SPM8). Results MRI: Onset-related activation was seen of the multisensory vestibular cortical network and ocular motor areas bilaterally, as well as of premotor area BA 6 (SMA). Block-related activation represented a subset of this activation pattern without SMA activation. PET: The PET data of the first stimulation blocks revealed prominent activation of the SMA and cerebellar vermis. MRI vs PET: Paired comparison showed significantly stronger SMA PET signals compared to block-related MRI that was not present for onset-related MRI. Conclusions The proposed procedure is suitable for direct statistical comparison of H 2 15 O-PET and fMRI activations during vestibular stimulation. At comparable spatial resolution, the higher temporal resolution of fMRI can be utilized to interpret the simultaneous PET data in another context. On the other hand, the quantitative nature of the PET data can augment the fMRI data that provide only an indirect measure of cortical processing. The most different effects were seen in the SMA, where the PET signal seems to reflect the onset-related MRI signal due to self-motion perception which is most prominent at stimulus onset causing a preparatory motor response.

Aim Some videooculography (VOG) studies have reported a spontaneous upbeat nystagmus (UBN) in the absence of fixation in a number of healthy subjects ( Bisdorff et al., 2000 ). These oscillations of the vertical gaze system are thought to be under the influence of the gravitational force vector, termed vestibular nystagmus. The neural basis of this UBN and whether structural differences can be attributed to it, however, remain unclear. Aim of our combined voxel-based morphometry (VBM) and VOG approach within the context of a larger vestibular stimulation study was to investigate the anatomical substrate of this UBN in healthy subjects. Methods 44 right-handed healthy subjects (21 F; mean age 28 years) were examined in supine position by means of VOG (EyeSeeCam©) without fixation before and after bimastoidal galvanic vestibular stimulation (GVS). Then structural and functional images were obtained in a clinical 3T scanner (Siemens Magnetom Verio, Erlangen, Germany) with a 32-channel head coil. The protocol included an isotropic (1 × 1 × 1 m) MPRAGE sequence and a resting-state session with 165 volumes, each consisting of 36 slices of a T2 ∗ -weighted ascending EPI sequence (TR 2.31s). Data analysis was performed using the VBM12 toolbox within SPM 12 (Version 6407 Wellcome Department of Imaging Neuroscience, London, UK) in Matlab 2015b (The MathWorks, Natick, Massachusetts, USA) after standard preprocessing. T-contrasts were calculated with respect to the rest condition and were considered significant at p Results In the VOG experiment, a spontaneous UBN occurred in 20 of 44 subjects (9 F) with a mean slow phase velocity (SPV) of 2,3°/s (SD = 1.1). After GVS, SPV decreased significantly by 52% (mean reduction of SPV = 1.06 °/s, SD = 1.0; paired t(19) = 0.03, p Conclusion Individual structural differences in the uvula could account for the physiological UBN in the absence of fixation in supine position. The uvula contributes to the processing of otolith information and responds both to translation and changes in orientation relative to gravity ( Angelaki et al., 2004 ). The tonsil on the other hand seems to be crucial for gaze-holding. Our results point to the importance of a balanced interplay of uvula and tonsil in vertical gaze control. The combination of a minimized influence of gravity on vertical eye movements in supine position and the absence of visual information might demask central oscillatory signals within the vertical gaze system. High frequency dampening via GVS might in return result in an artificial external stabilization of this system, reflected in a decrease of UBN. Supported by the German Foundation for Neurology (DSN) and the German Research Foundation.

The temporary improvement of visuospatial neglect during galvanic vestibular stimulation (Scand. J. Rehabil. Med. 31 (1999)117) may result from correction of the spatial reference frame distorted by the responsible lesion. Prior to an investigation of the neural basis of this effect in neurological patients, exploration of the neural mechanisms underlying such procedures in normals is required to provide insight into the physiological basis thereof. Despite their clinical impact, the neural mechanisms underlying the interaction of galvanic (and other) vestibular manipulations with visuospatial processing (and indeed the neural bases of how spatial reference frames are computed in man) remain to be clarified. We accordingly used fMRI in normal volunteers to investigate the effect of galvanically induced interference with the egocentric spatial reference frame on the neural processes underlying allocentric visuospatial (line bisection) judgments. A significant specific interaction of galvanic vestibular stimulation with the neural mechanisms underlying allocentric visuospatial judgments was observed in right posterior parietal and ventral premotor cortex only. Activation of these areas previously found to be damaged in visuospatial neglect suggests that these effects reflect the increased processing demands when compensating for the distorted egocentric spatial reference frame while maintaining accurate performance during the allocentric spatial task. These results thus implicate right posterior parietal and right ventral premotor cortex in the computation of spatial reference frames. Furthermore, our data imply a specific physiological basis for the temporary improvement of visuospatial neglect in patients with right hemisphere lesions during galvanic vestibular stimulation and may thus impact upon the rehabilitation of neglect: understanding the interaction of galvanic vestibular stimulation with allocentric visuospatial judgments in healthy volunteers may lead to the more effective deployment of such techniques in neurological patients.

Several works have revealed a robust visual–vestibular interaction at the cortical level in humans. The same has been shown at an infratentorial level in other primates. Most stimuli applied in the context of ocular motor neuroimaging research are fixed and therefore highly artificial in nature for methodological reasons. Advances in imaging techniques now allow for robust brainstem fMRI, thus opening up a whole new terrain for investigation. The aim of this study was to investigate the neural correlate for ocular motor adaption control (AC) with changing stimulus parameters (speed/direction) and the functional connectivity (FC) of the localised governing hubs at the level of the brainstem and the cerebellum. The effects of constant and linear accelerating small-field optokinetic (OKN) stimuli in the horizontal and vertical direction were studied in 20 volunteers lying supine with their ears plugged in a clinical 3T scanner (Siemens Magnetom Trio, Erlangen, Germany). The protocol included two sessions, each consisting of a T2*-weighted EPI sequence (2mm isotropic resolution, TA 2.93s) in alternating blocks of visual fixation and during OKN stimulation (left/right, up/down). Horizontal (vertical) OKN speeds were either fixed at 30°/s (20°/s) or accelerated during stimulus blocks from 15° to 45°/s (10°/s–30°/s). Resting-state data was acquired prior to task fMRI for 5min (3mm isotropic resolution, 37 slices, TA 2.67s, whole-brain coverage). Data was analysed with SPM8 and DPARSFA after standard preprocessing. T-contrasts were calculated with respect to the rest condition and were considered significant at p . The task revealed a cerebellar network including the dorsal ocular motor vermis (OMV), the fastigial ocular motor region, the posterior inferior vermis, the flocculus and paraflocculus, the culmen (lobule VI) and the declive. In the brainstem, we were able to significantly activate the ocular motor and abducens nuclei, the paramedian pontine reticular formation (PPRF), the dorsolateral pontine nucleus (DLPN), the nucleus reticularis tegmenti pontis (NRTP), the prepositus nucleus (NPH), riMLF and the interstitial nucleus of Cajal (INC). AC was localised to the OMV and pontine structures (NTRB and PPRF). Activation clusters throughout all OKN tasks were significantly larger with higher peak maxima in the left cerebellar hemisphere. We found a significant deactivation of the ventral uvula and the cerebellar tonsils (lobule VIII) during constant more so than during accelerating OKN stimulation. FC maps with the dorsal ocular motor vermis as a seed region gave a significant connectivity with all other regions found in the task-based part of our experiment as well as the dorsal visual stream and all cortical eyefields. Our study gives in vivo evidence for the basic visual–vestibular interactions at the level of the infratentorial networks. Ocular motor areas of the human brainstem could be mapped at an unprecedented detail. AC for the OKN task itself independent of direction was found to be localised mainly in the OMV. Velocity-fixed more so than accelerating OKN stimuli lead to a significant deactivation of a cerebellar core vestibular area known to govern the velocity storage mechanism, the ventral uvula. Extending the cortical concept of a right-hemispheric predominance for visual-spatial processing we found a complementary left-sided dominance for OKN responses in the cerebellum (Dieterich et al., 2003). Taken together, these findings should open up another chapter in our understanding of visual–vestibular interactions in the human brain.

Introduction In a recent epidemiologic study 5.3% of patients with parkinson disease (PD; mean age 70.5years) and up to 11% of PD patients with self-reported vertigo and dizziness had a benign paroxysmal positional vertigo (BPPV) (VanWensen et al., 2013). The prevalence of PD in industrialized countries is generally estimated at 0.1– 0.3% of the entire population (mean age German population ∼44years). It is more common in the elderly, where prevalences rise from 1.8% in those over 65years of age to 2–3% in the population over 80years (Official guidelines of the German Neurological Society, 2012; De Lau and Breteler, 2006). Thus, two questions arise: first, whether the prevalence of PD is increased in patients with diagnosed BPPV, and secondly, whether the prevalence of parkinson symptoms differs in patients with BPPV compared to those with other peripheral vestibular syndromes such as an unilateral peripheral vestibular loss (vestibular neuritis, VN) or Meniere‘s disease (MD). Methods All patients with diagnosed BPPV ( n =2347), MD ( n =1481) and VN ( n =713) seen in an interdisciplinary dizziness unit as well as in the German Center for Vertigo and Balance disorders of the Munich University between 2004 and 2013 were retrospectively analysed concerning their signs and symptoms of PD. All patients routinely underwent a detailed neurological examination and detailed vestibular testing. The parkinson symptoms were retrospectively classified according to the modified Hoehn and Jahr scale (Goetz, 2004). Results The prevalence for parkinson symptoms in the total BPPV group (mean age 59years) was 1.1%. In the subgroups of BPPV patients >65years of age it raised to 2.6% ( n =25), >70years to 3.5% ( n =23; mean age 77years), and >80years to 4.5% ( n =8). The parkinson symptoms were only mild (Hoehn and Jahr stages ⩽ 2 in the great majority of patients; only 4 patients at stage 3). In VN (mean age 55years) and MD (mean age 59years) the prevalences lay within the range of the normal population: 0.1% in all VN patients, respectively 0.5% in those >65years ( n =1); 0.3% in MD patients, respectively 0.7% in those >65years ( n =4). Conclusions Among patients with peripheral vestibular disorders only the BPPV patients showed a slightly increased prevalence of parkinson symptoms compared to the general population (2.6% vs. 1.8% in patients >65years). However, the prevalence for PD in BPPV patients (3.5% >70years, mean age 77years) seems to be lower than the prevalence for BPPV in PD (5.3% at a mean age of 70.5years) at least in less severely affected patients that can visit an outpatient clinic.

Background and aim Reactive gliosis may be beneficial for central compensation after unilateral inner ear damage. The aim of the present study was to visualize whole brain glial activation in vivo and over time by serial [ 18 F]-GE180- μ PET in a rat model of chemical unilateral labyrinthectomy (UL). Methods Ten Sprague–Dawley rats underwent a left-sided UL by transtympanic injection of bupivacaine and arsenilate, ten rats received a left-sided middle-ear injection of saline as a control group. Behavioural testing for symptoms of vestibular tone imbalance including registration of nystagmus and postural asymmetry was performed 1 day before and at days 1, 3, 7, 15, 30 after UL/sham injection. For functional imaging of glial activation, whole-brain μ PET with [ 18 F]-GE180, a novel translocator protein (tspo) ligand, was performed before and on 7, 15, 30 days after UL/sham injection. In vivo autoradiography was done at the respective time points for crosscheck and combined with Nissl-staining of the corresponding slices for detailed anatomic mapping. Results All rats showed clinical signs of an acute vestibular syndrome following UL with a maximum at 2 and 3 days. Nystagmus disappeared until day 5, postural asymmetry decreased significantly until day 15. In the UL group, [ 18 F]-GE180- μ PET depicted a glial activation in the ipsilesional vestibular, cochlear and facial nucleus at day 7, which further increased until day 15 and was only slightly visible at day 30. In addition no other regions of the brain showed signs of glial activation. In the sham group, glial activation was found in the facial nucleus at day 7 and 15. The time course and anatomic localization of glial activations were confirmed by in vivo [ 18 F]-GE180 autoradiography and Nissl-staining. Conclusions Glial activation takes place in the ipsilesional vestibular and cochlear nucleus within the first 30 days after an inner ear lesion and thereby parallels the establishment of central vestibular compensation. μ PET is a feasible method to show upregulation of the tspo protein in vivo as a sign of reactive gliosis induced by unilateral labyrinthectomy. Our data suggest that synthetic tspo ligands may be a novel therapeutic principle to augment central vestibular compensation.

Objectives Acute peripheral vestibular failure (VF) and neglect show similarities in clinical presentation and neglect can be ameliorated by vestibular stimulation. Furthermore, cortical areas involved in neglect patients overlap in part with the multisensory cortical vestibular network ( Karnath and Dieterich, 2006 ). Thus, the question did arise whether acute VF can induce spatial neglect. The aim of the current study was to find out whether patients with an acute VF show spatial neglect and if test scores were related to the severity of the deficit. Methods 28 patients with acute VF were assessed for signs of vestibular deficits and spatial neglect clinically as well as with common standard paper pencil neglect testing (bells test ( Gauthier et al., 1989 ), Albert’s test ( Albert, 1973 ), line bisection task ( Schenkenberg et al., 1980 ), figure copying). The laterality in the cancellation tasks was further analyzed using the Center of Cancellation method (CoC) ( Rorden and Karnath, 2010 ). The deficit was correlated with deviation of subjective visual vertical (SVV) and the degree of canal paresis. Results All patients had clear peripheral vestibular deficit at the time of testing. Mean time from symptom onset to neglect testing was 1.8 days (SD 1.7 d), to SVV testing 1.9 days (SD 1.8 d, mean deviation ± 7.3°) and to caloric testing 2.3 days (SD 2.3, mean reduction of caloric excitability 51%). Three patients showed pathologic scores in neglect tests (10%), two contralesionally and one ipsilesionally. One of these patients had a score fulfilling the criteria for spatial neglect in the bells test ( Gauthier et al., 1989 ) but not in the CoC method ( Rorden and Karnath, 2010 ). In contrast, the patient with a pathological CoC score did not meet the criteria for spatial neglect using the original method. One patient omitted one line in the Albert’s test contralaterally. Only one patient had pathological test scores in two tests but deviations in line bisection were both ipsilateral and contralateral. No patient showed congruent bias to one side in two different tests or analysis methods. There was no significant correlation between the total number of omissions in the bells test and the magnitude of SVV deviation or canal paresis. A group wise comparison of patients with and without pathological scores was carried out but the effect size was not strong enough to produce reliable results due to the small number of three patients. Conclusions VF patients occasionally showed pathological scores on single and different neglect tests. No correlation was found between omissions and SVV deviation or canal paresis. The three patients with pathologic scores did not show neglect behavior and the pattern of omissions is far less pronounced in the patients with VF compared to neglect patients. Thus, we suggest that these findings represent an attentional deficit and that novel tools to assess this deficit are needed. These should take spatial exploration and attention in a three-dimensional space into account to differentiate an attentional from a true spatial deficit. Acknowledgements This study was supported by the German Federal Ministry of Education and Research (BMBF, grant code 01 EO 0901) and the German Foundation for Neurology to MD.

Phobic Postural Vertigo (PPV) is a disabling disease with explicit psychosomatic aspects and comorbid depressive and anxiety disorder (Lahmann et al., in press; Ferreira et al., 2010). Transcranial direct current stimulation (tDCS) has been proven to improve depressive symptoms (Mondino et al., 2014; Shiozawa et al., 2014). In this small pilot trial, 8 patients were treated with tDCS (2mA, 20min, anode: F3, cathode: FP2) over five days. Follow-up measures were performed after 1, 2, and 4weeks. tDCS was well tolerated and no adverse effects occurred. Mean score of Vertigo Symptom Scale at baseline was 59±26, mean age was 45±12years. Mean Beck Depression Inventory was 15 points at baseline, mean HADS 16 points, Dizziness Handicap Inventory mean sum score was 48 at baseline. Hospital Anxiety and Depression Scale and Dizziness Handicap Inventory showed significant improvement over time course ( p =0.0002–0.007, t -test, two-tailed, Bonferroni-corrected to level of significance p ⩽0.01) and a moderate to high correlation over time course ( r =0.469–0.858, Pearson), whereas Beck Depression Inventory showed no changes over time course (Figs. 1 and 2). Age was not correlated to clinical improvement. Dizziness at baseline was not correlated to depression ratings. Although this small open study needs confirmation with objective rating instruments such as gait control (Schniepp et al., 2014; Schniepp et al., xxxx), tDCS seems to be a promising tool for the improvement of depression and anxiety as well as vertigo in PPV patients.

Downbeat and upbeat nystagmus can be classified as central vestibular syndromes in the vertical (pitch) plane of the vestibulo-ocular reflex (VOR) which are defined by ocular motor, perceptual, and postural manifestations. While the ocular motor syndrome was often studied investigations on the perceptual consequences for spatial orientation and motion perception are rare. Subjective visual straight ahead (SVA) and perception of object motion were measured in 11 patients with downbeat ( n =6) and upbeat ( n =5) nystagmus. Upward deviations of SVA (median +5.2°) were found in downbeat nystagmus, and downward deviations (median −7.8°) in upbeat nystagmus. SVA was deviated toward the slow phase of the vertical nystagmus in the pitch plane and associated with increased fore-aft body sway. Perception of object motion was more severely impaired for vertical (particularly for motion in the direction of slow nystagmus phases) than for horizontal directions in both downbeat and upbeat nystagmus. Impairment of motion perception in the vertical pitch plane of the VOR is beneficial to the extent that it alleviates disturbing oscillopsia due to the involuntary retinal slip. Thus, our findings confirm the hypothesis that downbeat and upbeat nystagmus reflect a central tone imbalance of the VOR in the vertical pitch plane with ocular motor, postural, and perceptual manifestations.

Background and aim Acute unilateral vestibular loss leads to vertigo sensation, nystagmus and postural imbalance. As a rule, a behavioral recovery of the signs and symptoms follows over days to months due to central vestibular compensation (VC). The present study aimed to investigate the influence of cerebral vascular lesions on VC by following a large cohort of patients after vestibular neuritis. Methods 235 patients (mean age: 54.2 ± 15.2, 53.4% men) with the clinical picture or history of an acute unilateral vestibulopathy, who were seen at the Department of Neurology and the German Center for Vertigo and Balance Disorders over the last 10 years, were included in the study. All patients underwent a detailed neuro-ophthalmological and neurological examination, including measures of the subjective visual vertical (SVV), ocular torsion (OT), head impulse test (HIT), provocation nystagmus (PN), visual acuity and postural control and were followed along their course of VC (mean number of visits 3.5 ± 1.2, mean time of follow-up 217 ± 625 days). In all patients a cranial MRI was available at onset of vestibular failure. The MRI was assessed by a two senior neuro-radiologist. Extent of supra- and infratentorial vascular white matter lesions was classified by the ARWMC scale (0–3 points). Strategic lesions in the vestibular network (medulla, vestibulocerebellum, thalamus) were registered separately. Patients were indicated as poorly compensated, if deviation of SVV (>2.5°), PN and postural asymmetry persisted for longer than 3 months after vestibular failure. Results 13.3% of patients were classified as poorly compensated at 3 months (PN: 55%, SVV deviation: 36%, postural asymmetry: 22%), 12.8% at 6 months and 10.6% at 12 months after acute unilateral vestibulopathy. These patients had significantly higher ARWMC scales as compared to patients with regular VC ( p Conclusions About 10% of patients have an impeded course of VC after acute unilateral vestibulopathy. Supratentorial vascular encephalopathy is a major risk factor for poor VC and should be considered to guide the intensity of physical treatment following acute unilateral vestibulopathy.

Background Gait disturbances are a common symptom in neurological disorders. About 70% of neurological inpatients show an abnormal gait. This results in decreased mobility, an increased risk for falls and therefore, a decrement in health-related quality of life. Instrumental gait analysis is used to characterize gait disturbances analyzing spatio-temporal parameters and video data. The aim of the study is to compare the clinical gait analysis with the standardized instrumental gait analysis. Methods/design Clinically confirmed cases of hypokinetic, atactic, phobic, paretic, antalgic, spastic, hyperkinetic and bizarre gait disturbances will be recruited for this prospective study. The patients will undergo 8 different gait measurements walking across a GAITRite® sensor carpet, while standardized gait parameters and video data are being collected. For analysis clinicians will be divided into 4 groups, each group will analyze the gait data of different packages with a limited data set (package 1: “video preferred walking speed”, package 2: “videos of all gait conditions”, package 3: “spatio-temporal gait parameters”, package 4: “all available data”). Sensitivity and specificity of the clinician’s diagnoses will be compared among the 4 groups. Furthermore, an automated pattern recognition system for gait pattern classification will be used to compare the computed results with the clinician’s results. Discussion This study investigates the use of different gait analysis methods and the automated pattern recognition procedures within neurological gait disorders. The comparison will determine the advantages and disadvantages of each method, which will further help to improve the instrumental and clinical gait analysis in the clinical routine.

Objective Determination of gait improvement after lumbar puncture (LP) in idiopathic normal pressure hydrocephalus (iNPH) is crucial, but the best time to do is unclear. We determined the time course of walking improvement after LP for single task (ST) and dual task (DT) walking in iNPH. Methods Sequential recordings of gait velocity of 24 patients (79.8 ± 7.8 years) prior to LP (TP0), on day 1 (TP1, 1-8 h), day 2 (TP2, 24 h), day 3 (TP3, 48 h), and day 4 (TP4, 72 h). Gait analysis was performed using a pressure sensitive carpet (GAITRite) under four conditions: walking at preferred velocity (STPS), walking at maximal velocity (STMS), dual-task “serial 7” (DTS7), dual-task “verbal fluency” (DTVF). Results Objective responder status moderately coincides with the self-estimation of the patients with high false positive subjective results (83%). The extent of improvement is higher for ST compared to DT (p〈0.05). Significant increases of walking speed were found at TP2 for STPS (p = 0.042), and DTVF (p = 0.046), and at TP3 for STPS (p = 0.035), DTS7 (p = 0.042), and DTVF (p = 0.044). The enlargement of ventricles (Evans Index) positively correlated with early improvement. Gait improvement at TP 3 correlated with the shunt response in 18 patients. Conclusions Quantitative gait assessment in iNPH is important due to the poor self-evaluation of the patients. The maximal increase in gait velocity can be observed 24–48 h after the LP. This time point is also best to predict the response to shunting. For DT paradigms the maximal improvement appears to be later (48–72 h). Assessment of gait should be performed at day 2 or 3 of LP.

Repetitive transcranial magnetic stimulation (rTMS) has been applied to sensory research and for the treatment of disorders in psychiatry and neurology since 1993 ( Wassermann and Zimmermann, 2012 ). The widespread cortical vestibular system, however, has to date not been targeted. Aim of our study was to manipulate vestibular regions in the human cortex by temporary virtual lesioning through rTMS and analyse the changes in the perception of a galvanic vestibular stimulation (GVS) as well as the differing activation patterns in functional neuroimaging. The effects of rectangular and sinusoidal bimastoidal GVS were studied in 16 healthy volunteers (8 F; mean age 23 years) in a 3T scanner. Data was analysed with SPM12. Results of the baseline fMRI session were used as functional localizers for three rTMS target regions: (1) cingulate sulcus visual (CSv) bilaterally, (2) the right inferior parietal lobule (BA40), and (3) the right polysensory superior temporal sulcus area (STP) ( Smith, 2012 ). The vestibular fMRI sessions with GVS were repeated within minutes after virtual lesioning of the target regions with low-frequency rTMS (1 Hz, 1800 pulses, 90% active motor threshold) followed by a psychophysical debriefing and a clinical neurootological examination. Generally speaking virtual lesioning of vestibular cortex areas by means of rTMS resulted in a reduced, never in a more pronounced, activation pattern of the cortical vestibular regions. (1) RTMS of area CSv bilaterally led to a reduction in vestibular activation of area 6, area MST, and the inferior parietal lobule in both hemispheres. For unilateral galvanic stimuli this effect was constricted to the cerebral hemisphere ipsilateral to the side of excitation. More subjects perceived their head to be rotating in space during sinusoidal GVS instead of the sensation of the whole body twirling compared to all other sessions (72% vs 30%). (2) Virtual lesioning of the right inferior parietal lobule lead to reduced activation of the target region itself and area 6 in the same hemisphere during GVS. Here, subjects showed the largest reduction in grading the perceived amount of rotation induced by rectangular GVS (mean reduction of 45 ± 7° compared to the baseline session). The effect of a significantly reduced sensation of head rotation during GVS was seen in all target areas. (3) RTMS of area STP lead to a significant isolated deactivation of the left midbrain during GVS. There were no pathological findings in our healthy subjects after the virtual lesioning in the ensuing clinical neurootological examinations. The realignment parameters of the vestibular stimulations as a correlate for a potential vestibular motor response also gave no significant differences between the four sessions. This is the first demonstration by means of psychophysics, fMRI and rTMS that points at the potential for a manipulation of vestibular cortex regions. Global cerebral network effects within the vestibular system were only seen after rTMS lesioning of the vestibular midline structure CSv bilaterally. The resulting shift from body to isolated head rotation in space in the perception after GVS for the lesioned area CSv could reflect its role in egomotion processing. The quantitative perceptual findings for the right inferior parietal lobule as an rTMS lesion site on the other hand might suggest a leading role for this region in egocentric referencing within the confines of a three-dimensional environment.

Motion correction algorithms are commonly used to correct for involuntary head motions in fMRI. We found that lid closure increased signal intensity of the eyes by a factor of 1.6 to 2 in EPI-fMRI. If the eyes were included in the scanning volume, transitions from eyes open to eyes closed in darkness were regularly associated with erroneously detected head translations along the z-axis and head rotations around the x-axis in Talairach's coordinate system. These artefacts could be avoided by masking the eyes in the images during the estimation of movement parameters.

The effect of unilateral sound stimulation (95 dB(A), 490 Hz) on antigravity muscles subserving postural balance, and on neck and forearm muscles was recorded in a patient with sound-induced oscillopsia, vertigo, and postural imbalance (otolithic Tullio phenomenon) using surface EMG electrodes; postural sway was measured while the patient stood upright with his eyes closed on a Kistler platform. The tibialis anterior and gastrocnemius muscles of the ipsilateral leg were coactivated at latencies as short as 47 ms (mean 58 ± 10 ms), with a weaker activation of the contralateral lower leg muscles following about 10 ms later. Neck muscles, triceps brachii, and forearm extensor muscles ipsilateral to the stimulated ear were activated at latencies as long as those of the lower leg muscles or often longer. Changes in posture, e.g. turning the head in either direction, balancing on one foot, and sitting or resting supine, as well as visual input modulated these early motor responses. They are thus of functional significance for counterregulating body perturbations and maintaining equilibrium in man. We conclude that otolithic input contributes directly to the control of posture and gait by fast descending pathways.

Background and aim Primary orthostatic tremor (OT) is a rare neurological disease of unknown pathophysiology characterized by a high frequency tremor mainly of the legs when standing. The aim of the present study was to depict the cerebral tremor network in OT by [ 18 F]-FDG-PET during standing. Methods Ten patients (mean age 58 ± 12 years) with neurophysiologically proven OT (EMG, posturography) and ten age-matched healthy controls were included in the study. All subjects underwent a [ 18 F]-FDG-PET paradigm during real standing (i.e. injection of [ 18 F]-FDG during upright stance, PET scan 30 min p.i.). As a control condition in a second session a PET was acquired after injection of [ 18 F]-FDG in lying position. PET images were processed by SPM8 software and compared between groups and conditions. Results All patients but no control subject showed a characteristic high-frequency peak at 12–16 Hz in posturography. In healthy subjects the regional cerebral glucose metabolism (rCGM) during standing compared to lying was increased in the vermal cerebellum, thalamus and primary motor region. During standing, OT patients had a relatively increased rCGM in the cerebellum (including the dentate nucleus), the ventrointermediate nucleus of the thalamus and the primary and supplementary motor cortex bilaterally in comparison to the control group. A relatively decreased rCGM was found in the mesiofrontal cortical areas in OT patients during standing. Conclusions In the present study a cerebello–thalamo–cortical tremor network is depicted in a group of OT patients using [ 18 F]-FDG-PET during standing. The data strongly reinforce the idea that the ventrointermediate nucleus of the thalamus may be a therapeutic target for deep brain stimulation in OT.

Introduction So far, studies in animals as well as humans gave evidence that damage to the peripheral vestibular system leads deficits in spatial memory and navigation by neuronal changes in the hippocampus (atrophy) and a general reorganization of the vestibular cortex network (Brandt et al., 2005; Eulenburg et al., 2010). Pathology of the peripheral-vestibular endorgan causes a range of cognitive deficits, not only spatial, but also non-spatial, like object recognition memory (Zheng et al., 2009; Andersson et al., 2003). Patients with a chronic bilateral vestibular failure (BVF) complain to troubled in their abilities to sustain attention. Until now, only few studies have used complex cognitive tasks to examine this empirically. Aim of this study was to test patients with chronic unilateral vestibular failure (UVF) and BVF systematically in a series of attentionale tests and analyze which domains are especially affected. Methods All patients underwent a neurological examination and detailed vestibular testing and were diagnosed on-site. Eight patients with UVF (4 female, mean age 59years, 2 lesions left-sided) and 16 BVF (8 female, mean age 59) executed the TAP Alertness and Visual Scanning, the TVA whole and partial report, the Stroop Test (ST) and the Digit Span Test (DST).The Wechsler Memory Test (MWT) and the Mini Mental Status Test (MMST) were used additionally to exclude negative influences on performance due to other cognitive impairments. Standard values exist for all tests (except TVA) and the deviation from the population average was calculated accordingly, using a One-sample T -Test. A T -value or PR-value below 43 was considered pathological (Zimmermann and Fimm, 2009). Results MMST and MWT were within a normal range in all patients. The ST and the DST showed no anomaly, however the variance was high. There was a mild effect in the TAP Alertness and in the TAP Visual Scanning performance in BVF patients. Their reaction times were slightly decelerated. In the TVA test attentionale selectivity was strongly affected in UVF patients, their attention was shifted to one side, which did not correlate with the lesion side. In both patient groups, the information processing speed and the short term memory capacity were reduced. Conclusion We found a set of cognitive tasks affected by the peripheral deficits, i.e. short term memory, processing speed of information, and especially in UVF attentionale selectivity. These cognitive deficits might be explained by pathways from the vestibular nuclei to the limbic system, the neocortex and other areas that are likely linked to non-spatial memory, such as the perirhinal cortex (Liu et al., 2004). Accordingly, the vestibular afferents appear to be necessary for many cognitive operations. This rearrangement after damage probably, includes some cognitive compromises. Forward-looking, more complex behavioral tests have to be developed and combined with functional to increase the understanding of how the vestibular system is involved in cognitive tasks and how vestibular damage can impair cognitive function. Acknowledgements Supported by the Graduate School of Neuroscience, the GRK, the German Federal Ministry of Education and Research (BMBF: IFB), and the German Foundation for Neurology (DSN).

Background and aims: The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target, thought to be particularly for useful in ameliorating gait disturbance in Parkinson’s disease. Recent evidence shows a prominent theta (4–7 Hz) rhythm in the PPN (Tsang et al., Neurology, 2010; Simon et al., J. Neurophysiol., 2010; Shimamoto et al., JNNP, 2010). Given that theta activity is modulated by vestibular signals elsewhere in the brain, e.g. hippocampus, (Shin, Synapse, 2010; Chen et al., Neuroimage, 2010), we assessed whether vestibular signals modulate PPN theta activity. Methods: We recorded local field potentials (LFPs) in three patients with implanted bilateral subthalamic nucleus (STN) and PPN DBS electrodes at 2000 Hz and filtered at 0.5–500 Hz at rest and during passive, yaw-plane whole body rotations (i.e., vestibular stimulation) at 0.2 and 0.4 Hz with eyes closed and then open with manifest vestibular ocular reflex activation (i.e., nystagmus) and then with VOR suppression (VORS). Frequency power spectra and the average power across a 1–1000 Hz frequency range were obtained. Results: PPN LFPs showed significant modulation during vestibular activation (rotations) compared to rest with power changes ca. four times larger than those found in the STN. The PPN LFP was dominated by theta (4–7 Hz) activity which was enhanced during all tasks compared to rest (including eyes open vs. closed at rest) except for VORS where there was a clear reduction in theta activity and this was more prominent for ‘fast’ (i.e., 0.4 Hz rotations) rotations. The pattern of theta activity was the same for right and left PPN including task-dependent modulation. To rule out the possibility that this theta activity was purely driven by nystagmus, we recorded LFPs during optokinetic nystagmus (OKN). OKN was associated with a decrease of theta power compared to rest. Conclusions: This is the first demonstration of vestibular modulation of PPN activity (in either animals or humans). Human PPN activity is increased during vestibular activation with a relative suppression of theta during VORS. This pattern of a reduction of activity during VORS compared to VOR is seen in the vestibular nuclei. Thus, the PPN may represent an important component of vestibular processing within the brainstem. We speculate that given the role of the vestibular system in balance and posture, PPN DBS may be work to improve gait and balance control via vestibular circuits.