Age Differences in Vestibular Processing: Neural and Behavioral Evidence

The vestibular system is well known for its role in balance, but its mechanisms of action in this role are not well understood. My dissertation aims to provide a better understanding of vestibular brain function, its correlation with postural control, and its alteration with advancing age. This is an important topic considering that falls are the current leading cause of injuries in older adults in the U.S., and they have negative consequences on wellbeing and independence. In this dissertation, I first review the conventional methods for studying vestibular function in the human brain, and I evaluate a novel MRI-compatible method, which relies on a pneumatic tapper. This approach successfully induces vestibular responses, while preventing the aversive effects of stimulation that are common in other approaches. Next, I assess age differences in brain responses to pneumatic vestibular stimulation, and find that older adults demonstrate less sensitivity to stimulation. Also, those with better postural control exhibit less deactivation of cross-modal sensory regions (e.g. visual and somatosensory cortices). This greater engagement of non-vestibular sensory regions in older adults with better balance could be a mechanism to compensate for inefficient vestibular processing. Consistent with this hypothesis, the relationship between postural control and deactivation of sensory regions was only evident in tasks of low difficulty (i.e. normal stance) in which compensatory neural recruitment might be most effective. After assessing the brain responses to vestibular stimulation in terms of activation and deactivation, I examine connectivity of the vestibular cortex with other regions. This last experiment demonstrates that vestibular cortex connectivity increases in response to vestibular stimulation, and young adults exhibit greater connectivity relative to older adults. Also, connectivity predicts postural stability in high difficulty tasks for young adults, and in low difficulty tasks for older adults. Better balance in young adults is associated with less vestibular connectivity (i.e. they engaged vestibular cortex more selectively), whereas better balance in older adults is associated with higher connectivity (i.e. more recruitment of other sensory regions). These findings reinforce the conclusions from the second experiment, and provide more evidence in support of the compensation related utilization of neural circuits hypothesis (CRUNCH) of neural processing in older adults.PHDKines & Psychology PhDUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/145857/1/fnoohi_1.pd

Cortical Effects of Noisy Galvanic Vestibular Stimulation Using Functional Near-Infrared Spectroscopy

Noisy galvanic vestibular stimulation (nGVS) can improve different motor, sensory, and cognitive behaviors. However, it is unclear how this stimulation affects brain activity to facilitate these improvements. Functional near-infrared spectroscopy (fNIRS) is inexpensive, portable, and less prone to motion artifacts than other neuroimaging technology. Thus, fNIRS has the potential to provide insight into how nGVS affects cortical activity during a variety of natural behaviors. Here we sought to: (1) determine if fNIRS can detect cortical changes in oxygenated (HbO) and deoxygenated (HbR) hemoglobin with application of subthreshold nGVS, and (2) determine how subthreshold nGVS affects this fNIRS-derived hemodynamic response. A total of twelve healthy participants received nGVS and sham stimulation during a seated, resting-state paradigm. To determine whether nGVS altered activity in select cortical regions of interest (BA40, BA39), we compared differences between nGVS and sham HbO and HbR concentrations. We found a greater HbR response during nGVS compared to sham stimulation in left BA40, a region previously associated with vestibular processing, and with all left hemisphere channels combined (p < 0.05). We did not detect differences in HbO responses for any region during nGVS (p > 0.05). Our results suggest that fNIRS may be suitable for understanding the cortical effects of nGVS

Widespread brain reorganization perturbs visuomotor coordination in early glaucoma

Glaucoma is the world’s leading cause of irreversible blindness, and falls are a major public health concern in glaucoma patients. Although recent evidence suggests the involvements of the brain toward advanced glaucoma stages, the early brain changes and their clinical and behavioral consequences remain poorly described. This study aims to determine how glaucoma may impair the brain structurally and functionally within and beyond the visual pathway in the early stages, and whether these changes can explain visuomotor impairments in glaucoma. Using multi-parametric magnetic resonance imaging, glaucoma patients presented compromised white matter integrity along the central visual pathway and around the supramarginal gyrus, as well as reduced functional connectivity between the supramarginal gyrus and the visual occipital and superior sensorimotor areas when compared to healthy controls. Furthermore, decreased functional connectivity between the supramarginal gyrus and the visual brain network may negatively impact postural control measured with dynamic posturography in glaucoma patients. Taken together, this study demonstrates that widespread structural and functional brain reorganization is taking place in areas associated with visuomotor coordination in early glaucoma. These results implicate an important central mechanism by which glaucoma patients may be susceptible to visual impairments and increased risk of falls

Neural Correlates of Vestibular Processing During a Spaceflight Analog With Elevated Carbon Dioxide (CO₂): A Pilot Study

Astronauts return to Earth from spaceflight missions with impaired mobility and balance; recovery can last weeks postflight. This is due in large part to the altered vestibular signaling and sensory reweighting that occurs in microgravity. The neural mechanisms of spaceflight-induced vestibular changes are not well understood. Head-down-tilt bed rest (HDBR) is a common spaceflight analog environment that allows for study of body unloading, fluid shifts, and other consequences of spaceflight. Subjects in this context still show vestibular changes despite being in Earth’s gravitational environment, potentially due to sensory reweighting. Previously, we found evidence of sensory reweighting and reduced neural efficiency for vestibular processing in subjects who underwent a 70-day HDBR intervention. Here we extend this work by evaluating the impact of HDBR paired with elevated carbon dioxide (CO₂) to mimic International Space Station conditions on vestibular neural processing. Eleven participants (6 males, 34 ± 8 years) completed 30 days of HDBR combined with 0.5% atmospheric CO₂ (HDBR + CO₂). Participants underwent six functional magnetic resonance imaging (fMRI) sessions pre-, during, and post- HDBR + CO₂ while we measured brain activity in response to pneumatic skull taps (a validated method of vestibular stimulation). We also measured mobility and balance performance several times before and after the intervention. We found support for adaptive neural changes within the vestibular system during bed rest that subsequently recovered in several cortical and cerebellar regions. Further, there were multiple brain regions where greater pre- to post- deactivation was associated with reduced pre- to post- balance declines. That is, increased deactivation of certain brain regions associated with better balance post-HDBR + CO₂. We also found that, compared to HDBR alone (n = 13 males; 29 ± 3 years) HDBR + CO₂ is associated with greater increases in activation of multiple frontal, parietal, and temporal regions during vestibular stimulation. This suggests interactive or additive effects of bed rest and elevated CO₂. Finally, we found stronger correlations between pre- to postHDBR + CO₂ brain changes and dependence on the visual system during balance for subjects who developed signs of Spaceflight-Associated Neuro-ocular Syndrome Frontiers in Systems Neuroscience | www.frontiersin.org 1 January 2020 | Volume 13 | Article 80Hupfeld et al. Neural Vestibular Processing With HDBR + CO₂ (SANS). Together, these findings have clear implications for understanding the neural mechanisms of bed rest and spaceflight-related changes in vestibular processing, as well as adaptation to altered sensory inputs

Direct comparison of activation maps during galvanic vestibular stimulation: A hybrid H-2[(15) O] PET-BOLD MRI activation study

Previous unimodal PET and fMRI studies in humans revealed a reproducible vestibular brain activation pattern, but with variations in its weighting and expansiveness. Hybrid studies minimizing methodological variations at baseline conditions are rare and still lacking for task-based designs. Thus, we applied for the first time hybrid 3T PET-MRI scanning (Siemens mMR) in healthy volunteers using galvanic vestibular stimulation (GVS) in healthy volunteers in order to directly compare (H2O)-O-15-PET and BOLD MRI responses. List mode PET acquisition started with the injection of 750 MBq (H2O)-O-15 simultaneously to MRI EPI sequences. Group-level statistical parametric maps were generated for GVS vs. rest contrasts of PET, MR-onset (event-related), and MR-block. All contrasts showed a similar bilateral vestibular activation pattern with remarkable proximity of activation foci. Both BOLD contrasts gave more bilateral wide-spread activation clusters than PET;no area showed contradictory signal responses. PET still confirmed the right-hemispheric lateralization of the vestibular system, whereas BOLD-onset revealed only a tendency. The reciprocal inhibitory visual-vestibular interaction concept was confirmed by PET signal decreases in primary and secondary visual cortices, and BOLD-block decreases in secondary visual areas. In conclusion, MRI activation maps contained a mixture of CBF measured using (H2O)-O-15-PET and additional non-CBF effects, and the activation-deactivation pattern of the BOLD-block appears to be more similar to the (H2O)-O-15-PET than the BOLD-onset

An assessment of cortical function in expert and novice surgeons

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Impact of Extremely Low-Frequency Magnetic and Electric Stimuli on Vestibular-Driven Outcomes

The vestibular system is extremely sensitive to electric fields (E-fields). Indeed, vestibular hair cells are graded potential cells and this property makes them very susceptible to small membrane potential modulations. Studies show that extremely low-frequency magnetic fields (ELF-MF) induced E-fields impact postural control in which the vestibular system plays an important role. However, the knowledge of whether this is indeed a vestibular specific effect is still pending. Considering its crucial role and the specific neurophysiological characteristics of its hair cells, the vestibular system emerges as an ELF-MF likely target The three studies presented in this thesis aimed to further address whether ELF-MF modulate vestibular-driven outcomes. Studies 1 and 2 aimed to investigate postural responses while more specifically targeting the vestibular system. However, we did not find any modulation in either study. Nonetheless, based on both studies, study 3 aimed to determine whether the orientation and frequency of our stimulations were more likely to target the otoliths. Therefore, the third study looked at the subjective visual vertical. Here, we found a potential ELF-MF utricular modulation. This thesis is the first steppingstone in a new field of research. Further investigations regarding the interaction between the ELF-MF and the vestibular system will have to look at more reflexives vestibular outcomes. Nonetheless, this thesis provides valuable information that will need to be taken into consideration when writing future international guidelines and standards related to ELF-MF

Neuronale Korrelate vestibulärer Stimulation

Das vestibuläre System als eines der evolutionär ältesten Systeme ist trotz der Häufigkeit des Symptoms Schwindel im Gegensatz zu den anderen sensorischen Systemen nur schlecht erforscht. Ziel der vorgelegten Studie war es mit Hilfe der EEG und der Bewegungsplattform das vestibuläre System von der Reizdarbietung bis zur kortikalen Verarbeitung vollständig darzustellen. Dabei konnte gezeigt werden, dass die EEG eine durchaus geeignete Methode ist, um das vestibuläre System auf kortikaler Ebene zu untersuchen. Konkret wurde gezeigt, dass passive translationale Beschleunigungen geeignet sind, vestibulär evozierte Potenziale (VestEPs) ähnlich dener in anderen Sinnessystemen auszulösen. Dabei konnten unabhängig von der Bewegungsrichtung drei Potenziale identifiziert werden, deren Amplituden durch die Beschleunigungsintensität moduliert werden. Eine Quellenlokalisation stellte das bereits aus fMRT- und PET-Studien bekannte, kortikale Netzwerk dar bestehend aus der hinteren Insel und dem Cingulum als zentrale Strukturen. Interessanterweise zeigte die bisher wenig beachtete Region CSv (visuelles Areal des Sulcus cingularis) die höchste Sensitivität für unterschiedliche Beschleunigungsintensitäten

Psychophysiological markers and the brain processing of visual motion induced nausea in healthy humans.

PhDBackground: Nausea is a common and complex multi-system sensation however objective psychophysiological markers of nausea that also predict nausea susceptibility in humans are lacking. In addition, the regions of the brain that process the sensation of nausea are unknown. Aim: To investigate the brain processing of nausea in healthy individuals. Methods: Study 1 validated the visual motion induced nausea paradigm with autonomic measures. Study 2 preselected nausea susceptible versus nausea resistant subjects using the stimulus with autonomic, electrogastrographic and cortisol monitoring. Study 3 investigated the brain processing of the nausea sensation and Study 4 identified which brain regions were specific to the generation of nausea. Results: Studies 1 and 2 – The stimulus was validated with stardardised questionnaires and identified nausea susceptible and resistant individuals with those susceptible demonstrating more anxiety; sympathetic arousal, parasympathetic withdrawal; shift from normogastria to dysrhythmia after motion video. Studies 3 and 4 – The inferior frontal gyrus was positively correlated with increasing nausea and the parahippocampus was inhibited. However, nausea resistant subjects demonstrated increased activity in the parahippocampus. The scopolamine study was overall inconclusive due to nausea being induced by the drug itself. Conclusion: NS subjects decreased parasympathetics, normogastria and increased sympathetics, anxiety and gastric dysrhythmias suggesting these parameters could be used as markers of nausea susceptibility. The inferior frontal gyrus and parahippocampus appears to play a role in nausea genesis and should be investigated further in patients or with other nauseogenic stimulus, newer functional brain imaging modalities, as well as different pharmacological modulation