The Untuned Visuo-temporal Cortex in Patients with Visual Snow

Visual snow (VS) is a distressing condition with persistent visual phenomena often leading to multiple unnecessary examinations and treatment attempts. VS impairs daily life by interfering with visual perception, particularly with reading. Neuronally, VS patients are thought to have differences in regional metabolism resulting in modulation of neuronal sensitivity and excitability. We hypothesize to see altered functional connectivity in patients with VS in brain regions associated with visual perception.

Department of Ophthalmology The untuned visuo-temporal cortex in visual snow Ghislaine L. Traber, MD March 19, 2019 NANOS Annual Meeting, Las Vegas No financial disclosures. Introduction - What is visual snow?  Visual disturbance - normal ophthalmic findings  Continuous perception of innumberable flickering dots «badly tuned analogue television»  Visual snow syndrome Schankin 2014  Palinopsia  Enhanced entoptic phenomena  Photophobia  Nyctalopia NANOS, Las Vegas, 2019  Non-visual symptoms  Migraine  Tinnitus Introduction - What is in the literature?  Disorder downstream the primary visual cortex Schankin 2014  Comorbid migraine very common Schankin 2014  No specific structural abnormalities in brain imaging studies Bessero 2014, Schankin 2014, Lauschke 2016  No regional functional changes in cerebral water diffusion and perfusion n=2; Jager 2005  Hypermetabolism right lingual gyrus and left cerebellar anterior lobe in FDG-PET imaging n=17 (migraine 14/17, migraine aura 5/17; 17 HC without migraine); Schankin 2014  Cortical hyperexcitability Chen 2011, McKendrick 2017  Thalamocortical dysrhythmia Lauschke 2016 NANOS, Las Vegas, 2019 The study - purpose  Functional and structural differences  Gray and white matter volume differences  Morphology and connectivity of the LGN  Investigating differences in resting state fMRI  spontaneous low-frequency fluctuations in the BOLD signal (BOLD = blood oxygenation level dependent)  in absence of external tasks or stimuli NANOS, Las Vegas, 2019 The study - purpose  Functional and structural differences  Gray and white matter volume differences  Morphology and connectivity of the LGN  Investigating differences in resting state fMRI   measure of resting state functional connectivity (rsFC) NANOS, Las Vegas, 2019 The study - methods  Adult patients  Diagnostic criteria for visual snow syndrome Schankin 2014  Recruited consecutively (University Hospital Zurich)  Age and sex matched healthy controls  3 Tesla MRI Scanner (Philips Healthcare)  T1weighted MPRAGE images  GMn and WMn MPRAGE images for LGN segmentation NANOS, Las Vegas, 2019 Results  Visual snow patients  N = 10  Age 32.5 years ± 10.7  Female 4/10  Normal ophthalmic exam  Healthy controls  N = 10  Age 33.2 years ± 8.9  Female 4/10  Normal ophthalmic exam  Mean duration 6.9 years  Associated symptoms/conditions NANOS, Las Vegas, 2019  Associated symptoms/conditions  1x floaters  1x occasional photopsias  1x episode of anxiety/depression Results - associated symptoms/conditions  Visual symptoms Palinopsia 3 Entoptic phenomena Photophobia Glare 8 6 5 Tinnitus Anxiety Nyctalopia 6 Symptoms in darkness & eyes closed 10  Associated conditions Migraine 5 NANOS, Las Vegas, 2019 With aura 4 8 4 Depression 5 (n = 10) Smaller LGN volume in visual snow  Mean LGN volumes  VS = 93.58 mm3  HC = 109.71 mm3  p = 0.045 Region-of-interest (ROI) analysis by four raters on subtracted image slices (GM nulled - WM nulled) NANOS, Las Vegas, 2019 Structural changes of the bilateral lingual gyrus  Bilateral lingual gyrus of VS patients show: derived from WFU PickAtlas  increased grey matter volume (GMV)  (R p = 0.026, L p = 0.020)  increased cortical thickness (CT)  R p = 0.038, L p = 0.032 lingual gyrus vision processing, related to letters NANOS, Las Vegas, 2019 Overlay of structural differences between visual snow patients and controls Increased and decreased resting state functional connectivity in visual snow  Striate/extrastriate visual cortex Imported from SPM12 anatomy toolbox Decrease in rsFC R FG4 - R hOc3d (p = 0.002)  Whole brain approach From FSL Harvard Oxford atlas Increase in rsFC L aMTG - L aITG L aMTG - L pITG NANOS, Las Vegas, 2019 (p = 0.001) (p = 0.001) Increased and decreased resting state functional connectivity in visual snow  Decrease in rsFC NANOS, Las Vegas, 2019  Increase in rsFC Increased and decreased resting state functional connectivity in visual snow  Decrease in rsFC  Increase in rsFC hOc3d / V3d contrast & motion stimuli FG4 / posterior fusiform area Motion & processing high-level visual information NANOS, Las Vegas, 2019 Increased and decreased resting state functional connectivity in visual snow  Decrease in rsFC MTG motion perception ITG motion perception, spatial attention, object recognition NANOS, Las Vegas, 2019  Increase in rsFC rsFC correlates with VS symptom duration  Connection L aMTG - L aITG correlates with symptom duration  p = 0.03, r = 0.68 Person's correlation of resting state functional connectivity (rsFC) strength with VS symptom duration NANOS, Las Vegas, 2019 Conclusions  Increased grey matter volume (GMV) and cortical thickness (CT) in bilateral lingual gyrus  Smaller LGN  Untuning the visuo-temporal cortex?  Hyperconnectivity between brain areas in the visuo-temporal cortex  Symptom duration correlated with resting state functional connectivity  Suggesting abnormal functional cross-talk in higher visual brain regions NANOS, Las Vegas, 2019 Acknowledgements NANOS 2018     Klara Landau Bujar Saliju Cyril Simmen Konrad Weber NANOS, Las Vegas, 2019     Spyridon Kollias Njoud Aldusary Lars Michels Marco Piccirelli       P. Freund A. Baeshen J. Alghamdi S. Pazahr R. Mazloum F. Alshehri Thank you for your attention! [e-mail] Corvatsch 3303m, by Konrad Weber NANOS, Las Vegas, 2019 NANOS, Las Vegas, 2019 fMRI - rsFC  SPM12 anatomy toolbox NANOS, Las Vegas, 2019  FSL Harvard Oxford Atlas A priori defined ROIs of the visual cortex  SPM12 anatomy toolbox Version 2.2c NANOS, Las Vegas, 2019 LGN imaging  Challenging  small and deeply located  Advanced resolution MPRAGE based structural imaging Aldusary, Michels et al. NeuroImage 2018  Delineate the borders of the LGN  Reliable assessment of LGN volume  Allow morphological comparisons between clinical populations Coronal LGN anatomical morphology (hypo-intensity relative to WM) with a motion corrected 0.4x0.4x0.4 mm3 3D T1 Turbo Field Echo (TFE) 7T image of the LGN (39 year-old male). Histology (78-year-old male, HistoDB 47293, stain: hematoxylin and eosin) kindly provided by Dr. E.J. Rushing, University Hospital Zurich, Department of Neuropathology. From Aldusary, Michels et al 2018 NANOS, Las Vegas, 2019 Positive correlation between grey matter volume and disease duration in the right lingual gyrus  P = 0.025 NANOS, Las Vegas, 2019 LGN volumes NANOS, Las Vegas, 2019 Clinical data NANOS, Las Vegas, 2019 Introduction - What is visual snow?  Visual disturbance - normal ophthalmic findings  Continuous perception of innumberable flickering dots («badly tuned analogue television»)  Visual snow syndrome  Palinopsia  Enhanced entoptic phenomena  Photophobia  Nyctalopia NANOS, Las Vegas, 2019 19.03.2019  Non-visual symptoms  Migraine  Tinnitus 26 Increased and decreased resting state functional connectivity in visual snow  Decrease in rsFC NANOS, Las Vegas, 2019  Increase in rsFC Increased and decreased resting state functional connectivity in visual snow  Decrease in rsFC  Increase in rsFC hOc3d / V3d contrast & motion stimuli FG4 / posterior fusiform area processing high-level visual information NANOS, Las Vegas, 2019 Increased and decreased resting state functional connectivity in visual snow  Decrease in rsFC  Increase in rsFC MTG Motion perception NANOS, Las Vegas, 2019 ITG object recognition, spatial attention, motion perception