Brain Functional Alterations in Patients With Benign Paroxysmal Positional Vertigo Demonstrate the Visual-Vestibular Interaction and Integration.

OBJECTIVE: This study aimed to analyze the features of resting-state functional magnetic resonance imaging (rs-fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. METHODS: A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed-based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. RESULTS: Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed-based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. CONCLUSION: The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.

Rod and frame test parameters for neuropsychology studies.

BACKGROUND: The rod and frame test (RFT), a measure of field dependence-independence, recently has reemerged as a measure of research interest and potential diagnostic value in neuropsychology. In the standard RFT, the subject experiences offsetting visual cues from a frame surrounding an embedded rod, while the subject's postural/vestibular cues provide the sense of verticality as the subject attempts to set the rod to vertical. The paper shows that RFTs not adhering to RFT parameters can reduce the test's visual framework impact experienced by the subject. Comparisons of neuropsychological studies will highlight that correct adherence to RFT testing conditions can strengthen RFT effects. METHOD: This review presents the parameters that have been studied which impact on subject performance on the RFT. It identifies how computer administered RFTs have been applied to enhance the study of the RFT parameters and make the RFT more accessible to the study of different diagnostic groups. The article also critiques studies by identifying how the RFT's parameters, study's design and statistical analysis may have diminished identifying the full effects of the RFT experience. RESULTS: Parameters impacting judgments of verticality of the rod can include: perceived size of rod and frame, the gap between the ends of the rod and surrounding frame, presentation of the rod within an encompassing 3D visual framework that visually blocks out the surrounding environment, a dark room, instructions stressing egocentric vs allocentric strategies, double frame surrounding the rod to assess global perception effects, etc. Details are presented how gap size likely affected results in neuropsychology studies. Potentially, these and other experiments may be studied using computer administered RFTs. CONCLUSIONS: Based on the descriptions of computer administered RFTs, this article suggested that incorporating these technologies can provide better understanding underlying the RFT, and in turn, understanding neuropsychology processes.

The Differentiation of Self-Motion From External Motion Is a Prerequisite for Postural Control: A Narrative Review of Visual-Vestibular Interaction.

The visual system is a source of sensory information that perceives environmental stimuli and interacts with other sensory systems to generate visual and postural responses to maintain postural stability. Although the three sensory systems; the visual, vestibular, and somatosensory systems work concurrently to maintain postural control, the visual and vestibular system interaction is vital to differentiate self-motion from external motion to maintain postural stability. The visual system influences postural control playing a key role in perceiving information required for this differentiation. The visual system's main afferent information consists of optic flow and retinal slip that lead to the generation of visual and postural responses. Visual fixations generated by the visual system interact with the afferent information and the vestibular system to maintain visual and postural stability. This review synthesizes the roles of the visual system and their interaction with the vestibular system, to maintain postural stability.

Effects of galvanic vestibular stimulation on resting state brain activity in patients with bilateral vestibulopathy.

We examined the effect of galvanic vestibular stimulation (GVS) on resting state brain activity using fMRI (rs-fMRI) in patients with bilateral vestibulopathy. Based on our previous findings, we hypothesized that GVS, which excites the vestibular nerve fibers, (a) increases functional connectivity in temporoparietal regions processing vestibular signals, and (b) alleviates abnormal visual-vestibular interaction. Rs-fMRI of 26 patients and 26 age-matched healthy control subjects was compared before and after GVS. The stimulation elicited a motion percept in all participants. Using different analyses (degree centrality, DC; fractional amplitude of low frequency fluctuations [fALFF] and seed-based functional connectivity, FC), group comparisons revealed smaller rs-fMRI in the right Rolandic operculum of patients. After GVS, rs-fMRI increased in the right Rolandic operculum in both groups and in the patients' cerebellar Crus 1 which was related to vestibular hypofunction. GVS elicited a fALFF increase in the visual cortex of patients that was inversely correlated with the patients' rating of perceived dizziness. After GVS, FC between parietoinsular cortex and higher visual areas increased in healthy controls but not in patients. In conclusion, short-term GVS is able to modulate rs-fMRI in healthy controls and BV patients. GVS elicits an increase of the reduced rs-fMRI in the patients' right Rolandic operculum, which may be an important contribution to restore the disturbed visual-vestibular interaction. The GVS-induced changes in the cerebellum and the visual cortex were associated with lower dizziness-related handicaps in patients, possibly reflecting beneficial neural plasticity that might subserve visual-vestibular compensation of deficient self-motion perception.

Attention Networks in the Parietooccipital Cortex Modulate Activity of the Human Vestibular Cortex during Attentive Visual Processing.

Previous studies in human subjects reported that the parieto-insular vestibular cortex (PIVC), a core area of the vestibular cortex, is inhibited when visual processing is prioritized. However, it has remained unclear which networks in the brain modulate this inhibition of PIVC. Based on previous results showing that the inhibition of PIVC is strongly influenced by visual attention, we here examined whether attention networks in the parietooccipital cortex modulate the inhibition of PIVC. Using diffusion-weighted and resting-state fMRI in a group of female and male subjects, we found structural and functional connections between PIVC and the posterior parietal cortex (PPC), a major brain region of the cortical attention network. We then temporarily inhibited PPC by repetitive transcranial magnetic stimulation (rTMS) and hypothesized that the modulatory influence of PPC over PIVC would be reduced; and, as a result, PIVC would be less inhibited. Subjects performed a visual attentional tracking task immediately after rTMS, and the inhibition of PIVC during attentive tracking was measured with fMRI. The results showed that the inhibition of PIVC during attentive tracking was less pronounced compared with sham rTMS. We also examined the effects of inhibitory rTMS over the occipital cortex and found that the visual-vestibular posterior insular cortex area was less activated during attentive tracking compared with sham rTMS or rTMS over PPC. Together, these results suggest that attention networks in the parietooccipital cortex modulate activity in core areas of the vestibular cortex during attentive visual processing.SIGNIFICANCE STATEMENT Although multisensory integration is generally considered beneficial, it can become detrimental when cues from different senses are in conflict. The occurrence of such multisensory conflicts can be minimized by inhibiting core cortical areas of the subordinate sensory system (e.g., vestibular), thus reducing potential conflict with ongoing processing of the prevailing sensory (e.g., visual) cues. However, it has remained unclear which networks in the brain modulate the magnitude of inhibition of the subordinate sensory system. Here, by investigating the inhibition of the vestibular sensory system when visual processing is prioritized, we show that attention networks in the parietooccipital cortex modulate the magnitude of inhibition of the vestibular cortex.

Increased brain responsivity to galvanic vestibular stimulation in bilateral vestibular failure.

In this event-related functional magnetic resonance imaging (fMRI) study we investigated how the brain of patients with bilateral vestibular failure (BVF) responds to vestibular stimuli. We used imperceptible noisy galvanic vestibular stimulation (GVS) and perceptible bi-mastoidal GVS intensities and related the corresponding brain activity to the evoked motion perception. In contrast to caloric irrigation, GVS stimulates the vestibular organ at its potentially intact afferent nerve site. Motion perception thresholds and cortical responses were compared between 26 BVF patients to 27 age-matched healthy control participants. To identify the specificity of vestibular cortical responses we used a parametric design with different stimulus intensities (noisy imperceptible, low perceptible, high perceptible) allowing region-specific stimulus response functions. In a 2 × 3 flexible factorial design all GVS-related brain activities were contrasted with a sham condition that did not evoke perceived motion. Patients had a higher motion perception threshold and rated the vestibular stimuli higher than the healthy participants. There was a stimulus intensity related and region-specific increase of activity with steep stimulus response functions in parietal operculum (e.g. OP2), insula, superior temporal gyrus, early visual cortices (V3) and cerebellum while activity in the hippocampus and intraparietal sulcus did not correlate with vestibular stimulus intensity. Using whole brain analysis, group comparisons revealed increased brain activity in early visual cortices (V3) and superior temporal gyrus of patients but there was no significant interaction, i.e. stimulus-response function in these regions were still similar in both groups. Brain activity in these regions during (high)GVS increased with higher dizziness-related handicap scores but was not related to the degree of vestibular impairment or disease duration. nGVS did not evoke cortical responses in any group. Our data indicate that perceptible GVS-related cortical responsivity is not diminished but increased in multisensory (visual-vestibular) cortical regions despite bilateral failure of the peripheral vestibular organ. The increased activity in early visual cortices (V3) and superior temporal gyrus of BVF patients has several potential implications: (i) their cortical reciprocal inhibitory visuo-vestibular interaction is dysfunctional, (ii) it may contribute to the visual dependency of BVF patients, and (iii) it needs to be considered when BVF patients receive peripheral vestibular stimulation devices, e.g. vestibular implants or portable GVS devices. Imperceptible nGVS did not elicit cortical brain responses making it unlikely that the reported balance improvement of BVF by nGVS is mediated by cortical mechanisms.

Changes in gain of horizontal vestibulo-ocular reflex during spaceflight.

BACKGROUND: The vestibulo-ocular reflex (VOR) is a basic function of the vestibular system that stabilizes gaze during head movement. Investigations on how spaceflight affects VOR gain and phase are few, and the magnitude of observed changes varies considerably and depends on the protocols used. OBJECTIVE: We investigated whether the gain and phase of the VOR in darkness and the visually assisted VOR were affected during and after spaceflight. METHODS: We measured the VOR gain and phase of 4 astronauts during and after a Space Shuttle spaceflight while the subjects voluntary oscillated their head around the yaw axis at 0.33 Hz or 1 Hz and fixed their gaze on a visual target (VVOR) or imagined this target when vision was occluded (DVOR). Eye position was recorded using electrooculography and angular velocity of the head was recorded with angular rate sensors. RESULTS: The VVOR gain at both oscillation frequencies remained near unity for all trials. DVOR gain was more variable inflight and postflight. Early inflight and immediately after the flight, DVOR gain was lower than before the flight. The phase between head and eye position was not altered by spaceflight. CONCLUSION: The decrease in DVOR gain early in the flight and after the flight reflects adaptive changes in central integration of vestibular and proprioceptive sensory inputs during active head movements.

Egocentric processing in the roll plane and dorsal parietal cortex: A TMS-ERP study of the subjective visual vertical.

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.

Functional correlate and delineated connectivity pattern of human motion aftereffect responses substantiate a subjacent visual-vestibular interaction.

The visual motion aftereffect (MAE) is the most prominent aftereffect in the visual system. Regarding its function, psychophysical studies suggest its function to be a form of sensory error correction, possibly also triggered by incongruent visual-vestibular stimulation. Several observational imaging experiments have deducted an essential role for region MT+ in the perception of a visual MAE but not provided conclusive evidence. Potential confounders with the MAE such as ocular motor performance, attention, and vection sensations have also never been controlled for. Aim of this neuroimaging study was to delineate the neural correlates of MAE and its subjacent functional connectivity pattern. A rotational MAE (n = 22) was induced using differing visual stimuli whilst modulating ocular motor parameters in a 3T scanner. Data was analyzed with SPM12. Eye movements as a response to the same stimuli were studied by means of high-resolution videooculography. Analysis for all stimuli gave bilateral activations along the dorsal visual stream with an emphasis on area MT. The onset of a visual MAE revealed an additional response in the right medial superior temporal area (MST) and a concurrent deactivation of vestibular hub region OP2. There was no correlation for the BOLD effects during the MAE with either ocular motor or attention parameters. The functional correlate of a visual MAE in humans may be represented in the interaction between region MT and area MST. This MAE representation is independent of a potential afternystagmus, attention and the presence of egomotion sensations. Connectivity analyses showed that in the event of conflicting visual-vestibular motion information (here MAE) area MST and area OP2 may act as the relevant mediating network hubs.

Mathematical Methods for Measuring the Visually Enhanced Vestibulo-Ocular Reflex and Preliminary Results from Healthy Subjects and Patient Groups.

BACKGROUND: Visually enhanced vestibulo-ocular reflex (VVOR) is a well-known bedside clinical test to evaluate visuo-vestibular interaction, with clinical applications in patients with neurological and vestibular dysfunctions. Owing to recently developed diagnostic technologies, the possibility to perform an easy and objective measurement of the VVOR has increased, but there is a lack of computational methods designed to obtain an objective VVOR measurement. OBJECTIVES: To develop a method for the assessment of the VVOR to obtain a gain value that compares head and eye velocities and to test this method in patients and healthy subjects. METHODS: Two computational methods were developed to measure the VVOR test responses: the first method was based on the area under curve of head and eye velocity plots and the second method was based on the slope of the linear regression obtained for head and eye velocity data. VVOR gain and vestibulo-ocular reflex (VOR) gain were analyzed with the data obtained from 35 subjects divided into four groups: healthy (N = 10), unilateral vestibular with vestibular neurectomy (N = 8), bilateral vestibulopathy (N = 12), and cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) (N = 5). RESULTS: Intra-class correlation index for the two developed VVOR analysis methods was 0.99. Statistical differences were obtained by analysis of variance statistical method, comparing the healthy group (VVOR mean gain of 1 ± 0) with all other groups. The CANVAS group exhibited (VVOR mean gain of 0.4 ± 0.1) differences when compared to all other groups. VVOR mean gain for the vestibular bilateral group was 0.8 ± 0.1. VVOR mean gain in the unilateral group was 0.6 ± 0.1, with a Pearson's correlation of 0.52 obtained when VVOR gain was compared to the VOR gain of the operated side. CONCLUSION: Two computational methods to measure the gain of VVOR were successfully developed. The VVOR gain values appear to objectively characterize the VVOR alteration observed in CANVAS patients, and also distinguish between healthy subjects and patients with some vestibular disorders.

Functional neuroimaging of visuo-vestibular interaction.

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

Age-associated differences in global and segmental control during dual-task walking under sub-optimal sensory conditions.

The ability to safely perform cognitive-motor dual-tasks is critical for independence of older adults. We compared age-associated differences in global and segmental control during dual-task walking in sub-optimal sensory conditions. Thirteen young (YA) and 13 healthy older (OA) adults walked a straight pathway with cognitive dual-task of walking-while-talking (WT) or no-WT under four sensory conditions. On randomly selected trials, visual and vestibular inputs were manipulated using blurring goggles (BV) and Galvanic Vestibular Stimulation (GVS), respectively. Gait speed decreased more in YA than OA during WT. Gait speed increased with GVS with normal vision but not BV. Step length considerably decreased with WT. Trunk roll significantly decreased only in OA with GVS in WT. Head roll significantly decreased with GVS regardless of age. Results indicate GVS-induced adaptations were dependent on available visual information. YA reduced their gait speed more than OA to achieve a similar pace to safely perform WT. GVS resulted in both age-groups to reduce head movement. However, with the addition of WT during GVS, OA also stiffened their trunk. Therefore, with increased attentional demands healthy OA employed different compensatory strategies than YA to maintain postural control.

Distortion of auditory space during visually induced self-motion in depth.

Perception of self-motion is based on the integration of multiple sensory inputs, in particular from the vestibular and visual systems. Our previous study demonstrated that vestibular linear acceleration information distorted auditory space perception (Teramoto et al., 2012). However, it is unclear whether this phenomenon is contingent on vestibular signals or whether it can be caused by inputs from other sensory modalities involved in self-motion perception. Here, we investigated whether visual linear self-motion information can also alter auditory space perception. Large-field visual motion was presented to induce self-motion perception with constant accelerations (Experiment 1) and a constant velocity (Experiment 2) either in a forward or backward direction. During participants' experience of self-motion, a short noise burst was delivered from one of the loudspeakers aligned parallel to the motion direction along a wall to the left of the listener. Participants indicated from which direction the sound was presented, forward or backward, relative to their coronal (i.e., frontal) plane. Results showed that the sound position aligned with the subjective coronal plane (SCP) was significantly displaced in the direction of self-motion, especially in the backward self-motion condition as compared with a no motion condition. These results suggest that self-motion information, irrespective of its origin, is crucial for auditory space perception.

Amplitude and frequency prediction in the translational vestibulo-ocular reflex.

The goal of this study was to assess the effect of amplitude and frequency predictability on the performance of the translational vestibulo-ocular reflex (tVOR). Eye movements were recorded in 5 subjects during continuous vertical translation that consisted of a series of segments with: 1) 3 amplitudes at constant frequency (2 Hz) or 2) 3 different frequencies (1.6, 2, 2.5 Hz). Stimulus changes were presented in a pseudo-random order. We found that there was little change in the tVOR immediately after an unexpected stimulus change, as if eye velocity were being driven more by an expectation based on previous steady-state motion than by current head translation. For amplitude transitions, only about 30% of the eventual response change was seen in the first half cycle. Similarly, a sudden change in translation frequency did not appear in eye velocity for 70 ms, compared to a 8 ms lag during similar yaw rotation. Finally, after a sudden large decrease in frequency, the eyes continued to track at the original higher frequency, resulting initially in an anti-compensatory tVOR acceleration. Our results elucidate further the complexity of the tVOR and show that motion prediction based on prior experience plays an important role in its response.