Reduced cortical folding in multi-modal vestibular regions in persistent postural perceptual dizziness

Abstract

Persistent postural perceptual dizziness (PPPD) is a common functional vestibular disorder that is triggered and sustained by a complex interaction between physiological and psychological factors affecting spatial orientation and postural control. Past functional neuroimaging research and one recent structural (i.e., voxel-based morphometry-VBM) study have identified alterations in vestibular, visuo-spatial, and limbic brain regions in patients with PPPD and anxiety-prone normal individuals. However, no-one thus far has employed surface based morphometry (SBM) to explore whether cortical morphology in patients with PPPD differs from that of healthy people. We calculated SBM measures from structural MR images in 15 patients with PPPD and compared them to those from 15 healthy controls matched for demographics, personality traits known to confer risk for PPPD as well as anxiety and depressive symptoms that are commonly comorbid with PPPD. We tested for associations between SBM measures and dizziness severity in patients with PPPD. Relative to controls, PPPD patients showed significantly decreased local gyrification index (LGI) in multi-modal vestibular regions bilaterally, specifically the posterior insular cortices, supra-marginal gyri, and posterior superior temporal gyri (p < 0.001). Within the PPPD group, dizziness severity positively correlated with LGI in visual areas and negatively with LGI in the right superior parietal cortex. These findings demonstrate abnormal cortical folding in vestibular cortices and correlations between dizziness severity and cortical folding in visual and somatosensory spatial association areas in PPPD patients, which provides new insights into the pathophysiological mechanisms underlying this disorder.

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 Template 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) (NIDCD, 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;Mahoney et al, 2013;Cousins et al, 2014) and treatment with serotonergic antidepressants and vestibular habituation are only partially successful (Staab et al, 2013). Adverse vestibularautonomic interactions (Fischl et al, 2008;Indovina et al, 2014Indovina et al, , 2015Staab et al, 2014;Riccelli et al, 2017a,b;Nigro 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.…”

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.…”