Altered Insular and Occipital Responses to Simulated Vertical Self-Motion in Patients with Persistent Postural-Perceptual Dizziness

Abstract

BackgroundPersistent postural-perceptual dizziness (PPPD) is a common functional vestibular disorder characterized by persistent symptoms of non-vertiginous dizziness and unsteadiness that are exacerbated by upright posture, self-motion, and exposure to complex or moving visual stimuli. Recent physiologic and neuroimaging data suggest that greater reliance on visual cues for postural control (as opposed to vestibular cues—a phenomenon termed visual dependence) and dysfunction in central visuo-vestibular networks may be important pathophysiologic mechanisms underlying PPPD. Dysfunctions are thought to involve insular regions that encode recognition of the visual effects of motion in the gravitational field.MethodsWe tested for altered activity in vestibular and visual cortices during self-motion simulation obtained via a visual virtual-reality rollercoaster stimulation using functional magnetic resonance imaging in 15 patients with PPPD and 15 healthy controls (HCs). We compared between groups differences in brain responses to simulated displacements in vertical vs horizontal directions and correlated the difference in directional responses with dizziness handicap in patients with PPPD.ResultsHCs showed increased activity in the anterior bank of the central insular sulcus during vertical relative to horizontal motion, which was not seen in patients with PPPD. However, for the same comparison, dizziness handicap correlated positively with activity in the visual cortex (V1, V2, and V3) in patients with PPPD.ConclusionWe provide novel insight into the pathophysiologic mechanisms underlying PPPD, including functional alterations in brain processes that affect balance control and reweighting of space-motion inputs to favor visual cues. For patients with PPPD, difficulties using visual data to discern the effects of gravity on self-motion may adversely affect balance control, particularly for individuals who simultaneously rely too heavily on visual stimuli. In addition, increased activity in the visual cortex, which correlated with severity of dizziness handicap, may be a neural correlate of visual dependence.

Cortical alterations in phobic postural vertigo – a multimodal imaging approach

“…Patients with visually induced dizziness, also known as visual vertigo, also show an increased connectivity between thalamus, occipital cortex, and cerebellar areas . Furthermore, during a self‐motion simulation in PPPD patients higher dizziness handicap values correlated positively with occipital activity . Thus, it seems possible that PPV patients shift their attentional focus toward mere visual information and as a consequence attenuate secondary visual integrating networks.…”

Persistent Postural-Perceptual Dizziness

“…Physiological, psychological, and advanced brain imaging studies published since that time have supported this conceptualization. 16,[33][34][35][36][37][38][39][40] As discussed earlier and shown on the left side of ►Fig. 2, PPPD may be triggered by neuro-otologic disorders, other structural or metabolic conditions, and psychological distress that cause vertigo, unsteadiness, or dizziness, or disrupt balance function.…”

“…2 and identified another pathophysiological process, namely, altered activity and connectivity in cortical networks in the brain that subserve spatial orientation and locomotion. [36][37][38][39][40] In a study using resting state functional magnetic resonance imaging (fMRI), patients with PPPD compared with healthy controls had widespread reductions in connectivity from the left hippocampus (responsible for egocentric spatial navigation) to multiple brain regions. In contrast, connectivity between regions of the frontal and occipital cortices was increased in relation to mild state anxiety, consistent with the concept of visual dependence as a key process in PPPD.…”

“…36 In a complementary fMRI investigation using visual motion stimuli from a virtual reality rollercoaster ride, patients with PPPD failed to activate the central insular sulcus (a region that helps resolve motion trajectories in gravity) compared with healthy controls, whereas they showed activation of primary visual cortical areas in proportion to the severity of their symptoms, again pointing to visual depen-dence as a crucial mechanism in PPPD. 37 Neuroimaging studies using advanced anatomical analyses have identified structural changes (reduced gray matter volumes 40 and decreased cortical folding 39 ) in some of the regions that showed reduced activity and connectivity in the functional imaging investigations. Given the cross-sectional design of those studies, it is not possible to know if the structural alterations were sequelae of alterations in functioning (i.e., the result of brain plasticity) or subtle, preexisting structural defects that predisposed patients to the development of PPPD.…”

Probabilistic atlas of the lateral parabrachial nucleus, medial parabrachial nucleus, vestibular nuclei complex and medullary viscero-sensory-motor nuclei complex in living humans from 7 Tesla MRI

“…According to the National Institutes of Health National Institute on Deafness and other Communication Disorders (NIDCD) -2016NIDCD Strategic Plan" 2015, chronic vestibular disorders (including chronic imbalance and dizziness) affect about 5 % of the American adult population, their mechanisms are not fully understood (Kitahara et al 1997;Ris et al 1997;Godemann et al 2005;Heinrichs et al 2007;Best et al 2009;Dutia 2010;E J Mahoney, Edelman, and D Cremer 2013;Cousins et al 2014) and treatment with serotonergic antidepressants and vestibular habituation are only partially successful (Staab, Balaban, and Furman 2013). Adverse vestibularautonomic interactions (Fischl et al 2008;Staab et al 2014;Indovina et al 2014Indovina et al , 2015Riccelli, Indovina, et al 2017;Riccelli, Passamonti, et al 2017a, 2017bNigro et al 2018;Passamonti et al 2018) appear to precipitate and perpetuate chronic vestibular disorders, crucially underlying the pathophysiologic process of these disorders. Our findings offer potential benefits to investigate the connectivity pathways of Ve and autonomic nuclei in living humans on widely available 3 Tesla scanners, and expand our knowledge of successful compensation for acute vestibular events versus development of chronic vestibular disorders.…”