The impact of vestibular modulations on whole brain structure and function in humans

The vestibular system is a sensory system that monitors active and passive headmovements while at the same time permanently sensing gravity. Vestibular information is important for maintaining balance and stabilisation of vision and ultimately for general orientation in space. A distributed set of cortical vestibular regions process vestibular sensory information, together with other sensory and motor signals. How these brain regions are influenced by or interact with each other, and how this depends on the context in which the system is acting is not well understood. In my research I investigated the whole brain consequences of different vestibular sensory contexts by means of structural and functional magnetic resonance (MR) imaging on three different time scales (long-term, short-term, and medium-term). For the long-term time scale, I investigated functional brain connectivity in individuals experiencing a type of chronic dizziness that cannot be explained by structural damage within the nervous system. These patients exhibit chronic or long-term alterations in their processing of vestibular information, which leads to dizziness and vertigo. I found altered sensory and cerebellar network connectivity when they experience a dizziness-provoking stimulus. These two networks contain, but are not limited to, vestibular processing regions, demonstrating the importance of a whole-brain approach. The alterations correspond the notion that these patients have dysfunctional stimulus expectations. The short-term vestibular processing I investigated was the effect of artificial vestibular stimulation, which is frequently used in vestibular research and treatment. For this, I analysed functional network connectivity in healthy participants. I found that short-term vestibular stimulation does not cause a cortical functional reorganisation, although a nociceptive stimulus, which was matched for the somatosensory component of this stimulation, led to a reorganisation. The fact that cortical reorganisation does not occur during exclusively vestibular stimulation may reflect subconscious nature of vestibular processing in that it does not induce a different internal brain state. On the medium-term time scale, I investigated whole-brain structural changes as a result of gravity. Astronauts that travel to space for extended periods of time experience several physiological symptoms also affecting the fluid exchange of the brain. To characterise if these fluid exchanges also affect size of the spaces around brain blood vessels (perivascular spaces), I developed a semi-automatic detection pipeline which requires only one type of structural MR image. I found that space travellers have enlarged perivascular spaces even before their mission, when compared to a control population. These spaces were to a small extend further increased shortly after a long duration space flight of 6 months. Astronaut training thus contributes to structural changes in the whole brain in combination with long-duration space flight. This further suggests that additional contextual factors such as sleep quality should be considered in the future. Overall, in my thesis I show that investigating the whole brain during different vestibular modulations provides additional and novel insights about the underlying neural processes. I found that long-term vestibular states have an impact on functional networks, whilst short-term vestibular modulations do not seem to impact functional network organisation. In addition, I quantified the structural impact of microgravity and astronaut training in the whole brain using a new analysis pipeline. In the future, I expect that new advancements in the field of neuroimaging analysis, such as high sampling of individuals and dynamic network analysis will advance the field. This will potentially also provide new means to monitor disease progression or intervention success

Delineating neural responses and functional connectivity changes during vestibular and nociceptive stimulation reveal the uniqueness of cortical vestibular processing

Vestibular information is ubiquitous and often processed jointly with visual, somatosensory and proprioceptive information. Among the cortical brain regions associated with human vestibular processing, area OP2 in the parietal operculum has been proposed as vestibular core region. However, delineating responses uniquely to vestibular stimulation in this region using neuroimaging is challenging for several reasons: First, the parietal operculum is a cytoarchitectonically heterogeneous region responding to multisensory stimulation. Second, artificial vestibular stimulation evokes confounding somatosensory and nociceptive responses blurring responses contributing to vestibular perception. Furthermore, immediate effects of vestibular stimulation on the organization of functional networks have not been investigated in detail yet. Using high resolution neuroimaging in a task-based and functional connectivity approach, we compared two equally salient stimuli-unilateral galvanic vestibular (GVS) and galvanic nociceptive stimulation (GNS)-to disentangle the processing of both modalities in the parietal operculum and characterize their effects on functional network architecture. GNS and GVS gave joint responses in area OP1, 3, 4, and the anterior and middle insula, but not in area OP2. GVS gave stronger responses in the parietal operculum just adjacent to OP3 and OP4, whereas GNS evoked stronger responses in area OP1, 3 and 4. Our results underline the importance of considering this common pathway when interpreting vestibular neuroimaging experiments and underpin the role of area OP2 in central vestibular processing. Global network changes were found during GNS, but not during GVS. This lack of network reconfiguration despite the saliency of GVS may reflect the continuous processing of vestibular information in the awake human

Network changes in patients with phobic postural vertigo

Introduction Functional dizziness comprises a class of dizziness disorders, including phobic postural vertigo (PPV), that cause vestibular symptoms in the absence of a structural organic origin. For this reason, functional brain mechanisms have been implicated in these disorders. Methods Here, functional network organization was investigated in 17 PPV patients and 18 healthy controls (HCs) during functional magnetic resonance imaging with a visual motion stimulus, data initially collected and described by Popp et al. (2018). Graph theoretical measures (degree centrality [DC], clustering coefficient [CC], and eccentricity) of 160 nodes within six functional networks were compared between HC and PPV patients during visual motion and static visual patterns. Results Graph theoretical measures analyzed during the static condition revealed significantly different DC in the default‐mode, sensorimotor, and cerebellar networks. Furthermore, significantly different group differences in network organization changes between static visual and visual motion stimulation were observed. In PPV, DC and CC showed a significantly stronger increase in the sensorimotor network during visual stimulation, whereas cerebellar network showed a significantly stronger decrease in DC. Conclusion These results suggest that the altered visual motion processing seen in PPV patients may arise from a modified state of sensory and cerebellar network connectivity

Delineating neural responses and functional connectivity changes during vestibular and nociceptive stimulation reveal the uniqueness of cortical vestibular processing

Vestibular information is ubiquitous and often processed jointly with visual, somatosensory and proprioceptive information. Among the cortical brain regions associated with human vestibular processing, area OP2 in the parietal operculum has been proposed as vestibular core region. However, delineating responses uniquely to vestibular stimulation in this region using neuroimaging is challenging for several reasons: First, the parietal operculum is a cytoarchitectonically heterogeneous region responding to multisensory stimulation. Second, artificial vestibular stimulation evokes confounding somatosensory and nociceptive responses blurring responses contributing to vestibular perception. Furthermore, immediate effects of vestibular stimulation on the organization of functional networks have not been investigated in detail yet. Using high resolution neuroimaging in a task-based and functional connectivity approach, we compared two equally salient stimuli-unilateral galvanic vestibular (GVS) and galvanic nociceptive stimulation (GNS)-to disentangle the processing of both modalities in the parietal operculum and characterize their effects on functional network architecture. GNS and GVS gave joint responses in area OP1, 3, 4, and the anterior and middle insula, but not in area OP2. GVS gave stronger responses in the parietal operculum just adjacent to OP3 and OP4, whereas GNS evoked stronger responses in area OP1, 3 and 4. Our results underline the importance of considering this common pathway when interpreting vestibular neuroimaging experiments and underpin the role of area OP2 in central vestibular processing. Global network changes were found during GNS, but not during GVS. This lack of network reconfiguration despite the saliency of GVS may reflect the continuous processing of vestibular information in the awake human