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Research ArticleResearch Article: New Research, Disorders of the Nervous System

Tug-of-Peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 Duplication Syndrome of Autism

Daria Bogatova, Stelios M. Smirnakis and Ganna Palagina
eNeuro 8 November 2023, 11 (1) ENEURO.0102-23.2023; https://doi.org/10.1523/ENEURO.0102-23.2023
Daria Bogatova
1Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115
2Department of Biology, Boston University, Boston, MA 02115
3Harvard Medical School, Boston, MA 02115
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Stelios M. Smirnakis
1Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115
3Harvard Medical School, Boston, MA 02115
4Jamaica Plain Veterans Affairs Hospital, Boston, MA 02130
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Ganna Palagina
1Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115
3Harvard Medical School, Boston, MA 02115
4Jamaica Plain Veterans Affairs Hospital, Boston, MA 02130
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  • Figure 1.
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    Figure 1.

    Bistable OKN responses under visual rivalry. A, Bistable moving plaid stimulus. Type I symmetric plaid is composed by summing two 50% contrast component gratings. The gratings move at an angle of 120° relative to each other. This plaid can be seen either as two individual gratings moving at an angle or as a sum of gratings integrated percept of pattern motion. The direction of pattern motion lies in between the directions of motion of each grating. Thus, the observer can follow three directions of motion (lower panel): pattern motion (direction set at 0°) and either of the component grating’s drift, offset at +60° and –60° from the vector of the plaid’s motion (insets). B, Experimental setup. We presented the stimuli on two screens positioned at equal distances from the mouse head to cover 180° of the mouse ipsilateral visual field. We head-posted the mouse to prevent head movements and monitored eye movements with an infrared camera. The mouse could walk freely on the free-moving wheel. Green arrows indicate the direction of the global drift of the stimulus. The stimulus was moving toward the mouse’s nose to induce robust optokinetic movements. C, D, E, Data preprocessing pipeline. C, OKN images were collected at 300 Hz and 20 randomly selected mouse pupil movies were used to train Deep Lab Cut ResNET-150 model to extract the position and size of the animal’s pupil during the OKN (colored dots DeepLabCut feature detection). D, The vertical and horizontal components of the OKN were sorted into saccade-pursuit eye movement pairs, and eye-blink and grooming-related artifacts were located using custom-written Python toolbox “Dolia” and excluded from analysis. E, The pursuit phases of the OKN eye movements were fitted with a linear polynomial fit. The ratio between fitted vertical and horizontal component of each eye movement was then used to determine its direction (angle). Pink and blue histograms show the example distributions of eye movement directions from two different 15-min OKN movies. Using the ratio of the vertical and horizontal components’ amplitudes, the directions of the eye movements were determined (for details, see Materials and Methods). Right, Distributions of the directions of pursuit phases of OKN for two different OKN movies. F, G, Grating-induced OKN. To determine the location of zero direction (pattern motion direction) and classify eye movements as aligned with pattern motion or alternatively the motion of the components, we used OKN data obtained by presenting the zero-direction grating moving in temporonasal direction, similarly to the plaid setup. Since such a grating has only one unambiguous direction of drift, it is possible to use the mean of the eye movement direction distribution as a zero direction. Additionally, [–SD, +SD] can be set as a bracket in which most eye movements aligned with zero direction fall (E). The grating-induced OKN is shown in F: as expected, OKN eye movements contain a sole horizontal component (black trace), with no consistent vertical deflections (red trace), and this stimulus does not result in visual rivalry as only one interpretation of the stimulus is possible. In G, the distribution of grating-induced OKN is shown (yellow histogram, 13 zero-direction grating movies from 13 animals were used to determine zero position, and the SD bracket for eye movement classification). [–SD, +SD] interval around the zero direction is then applied to plaid OKN data: the eye movements with directions inside this interval are classified as pattern-motion aligned, while eye movements with directions outside of this interval are classified as component-motion aligned (G, blue histogram). H, I, Plaid-induced OKN shows bistable reversals of the eye movement directions. In H, the mouse can follow either the plaid or the grating direction while observing the unchanging plaid stimulus. Green dotted line indicates location of the perceptual switch, defined as the start of the saccade where the animal starts following a different stimulus interpretation. Initially, the animal follows a pattern motion direction; after the reversal, a solid vertical component appears (red trace) as the animal stops following the pattern motion and starts following the +60° component. I, Blue histogram, The EM directions distribution of OKN induced by a plaid stimulus. Gray dotted lines correspond to the pattern-component OKN bracket derived from grating OKN data (see the yellow histogram in G). Plaid OKN: central peak corresponding to pattern-motion aligned eye movements as well as two additional peaks located at approximately +60° and –60° off the central peak and corresponding to component motion-aligned OKN.

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    Figure 2.

    MECP2 duplication syndrome results in reduced perceptual reversal rate during visual rivalry. White bars, littermates; blue bars, MECP2 duplication syndrome. A, The reversal rate (per minute of OKN) is consistently lower in MECP2-ds than in normal littermates. Left panel, Raw data. Right panel, Data normalized by maximum inside each littermate, MECP2 duplication pair. Reversals per minute: littermates, mean ± SEM: 2.8 ± 0.58 , median: 2.05; MECP2-ds, mean ± SEM: 1.895 ± 0.325 , median: 1.485. B, The distribution of perceptual reversal rates of individual OKN periods. Left panel (white bars), Littermates. Right panel (blue bars), MECP2 duplication. The distributions follow γ distribution fit (littermates: p<0.0001 ; MECP2-ds: p<0.0001 , χ2 test). Data were pooled across OKN periods belonging to 13 littermates and 13 MECP2 duplication animals, respectively. Before pooling, each animal’s dataset was normalized by its mean rate. C, In accordance with the reduced reversal rate in MECP2 duplication, the probability of observing a switch after 1 min of ongoing plaid-induced OKN was also reduced in MECP2 duplication mice. The left panel indicates raw data, while the right panel shows the data normalized by maximum inside each littermate, MECP2 duplication pair. Reversal probability: littermates, mean ± SEM: 0.4425 ± 0.054 , median: 0.407; MECP2-ds mean ± SEM: 0.284 ± 0.028 , median: 0.308. D, MECP2 duplication mice consistently show a substantial fraction of OKN periods where no reversals occur, and the animal persistently tracks either pattern (“coherent” percept) or component direction (“transparent” percept). Left panel, Raw data. Right panel, Data normalized by maximum inside each littermate, MECP2 duplication pair. Nonreversal OKN fraction: littermates, mean ± SEM: 0.33 ± 0.055 , median: 0.374; MECP2-ds, mean ± SEM: 0.555 ± 0.04 , median: 0.54. All p-values are determined by two-sided Wilcoxon signed rank (WSR) test, n=13 pairs. Wilcoxon test statistic, p-values, z-scores and effect sizes for panels A, C and D are reported in Table 1.

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    Figure 3.

    Atypical preference for local motion processing in MECP2 duplication syndrome. The reduced rate of perceptual reversals in MECP2 duplication mice is driven by the lengthening and overstability of component motion (“transparent”) percepts. CM, component movement; PM, pattern movement. A, The total fraction of nystagmoid eye movements aligned with pattern motion direction (“coherent” percept). Although there is considerable variance across data, in normal littermates (clear bar), nearly equal fractions of eye movements are aligned to either pattern motion direction (“coherent” percept, global motion) or component motion direction (“transparent” percept, local motion). In contrast, in MECP2 duplication mice, a greater portion of OKN eye movements is allocated to component local motion, and the fraction of pattern motion-aligned eye movements is reduced. Littermates, mean ± SEM: 0.538 ± 0.064 , median: 0.53; MECP2-ds, mean ± SEM: 0.339 ± 0.055 , median: 0.326. Left panel, Raw data. Right panel, Data normalized by maximum inside each littermate, MECP2 duplication pair. B, Dominance duration is increased in MECP2 duplication mice, following the decrease in reversal rate and reversal probability (Fig. 2). Littermates, mean ± SEM: 25.2 ± 4.5 , median: 21; MECP2-ds, mean ± SEM: 36.7 ± 8 , median: 25. Left panel, Raw data. Right panel, Data normalized by maximum inside each littermate, MECP2 duplication pair; p-values, WSR. C, D, The increase in average dominance duration is carried mainly by the increased durations of “transparent” percepts when the mouse is following the local motion of component gratings (C, littermates, mean ± SEM: 27.5 ± 7.11 , median: 20.2; MECP2-ds, mean ± SEM: 49.2 ± 11.5 , median: 31), while the global motion “coherent” percepts show inconsistent changes with shortening in some animals and lengthening in others (D, littermates, mean ± SEM: 21.2 ± 4.7 ; MECP2-ds, mean ± SEM: 13.36 ± 2.2 ). As a result, although there is a general trend of shorter pattern-motion percepts in MECP2 duplication mice, it is not significant (p=0.1677 ). Left panels, Raw data. Right panels, Data normalized by maximum inside each littermate, MECP2 duplication pair. E, The ratio of dominance period durations is shifted in favor of transparent local motion percepts at the expense of global motion “coherent” percepts. Littermates, mean ± SEM: 1.376 ± 0.41 , median: 0.82; MECP2-ds, mean ± SEM: 2.2 ± 0.48 , median: 1.38. Left panel, Raw data. Right panel, Data normalized by maximum inside each littermate, MECP2 duplication pair. F, The number of eye movements per minute in WT and MECP2-duplication mice. Littermates, mean ± SEM: 11.38 ± 1.81 , median: 12.37; MECP2-ds, mean ± SEM: 9,07 ± 1.41 , median: 7.54. These results indicate that the difference in frequency of eye movement is not significant (p=0.6848 ). Left panel, Raw data. Right panel, Data normalized by maximum inside each littermate, MECP2 duplication pair. White bars, Littermates. Blue bars, MECP2 duplication. All p-values are determined by two-sided Wilcoxon signed rank (WSR) test, unless noted otherwise, n=13 pairs. Wilcoxon test statistic, p-values, z-scores and effect sizes for panels A-F are reported in Table 1.

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    Table 1

    Statistical table

    Figurep-valuez scorer (effect size)W (Wilcoxon)
    2A0.01342.410.66980
    2C0.01422.3770.6679.5
    2D0.0027−2.8−0.77555.5
    3A0.00172.90.804487
    3B0.0342−2.12−0.58712
    3C0.0081−2.551−0.70759
    3E0.0161−2.353−0.6539
    3D0.1677 (not significant)
    3F0.6848 (not significant)
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Tug-of-Peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 Duplication Syndrome of Autism
Daria Bogatova, Stelios M. Smirnakis, Ganna Palagina
eNeuro 8 November 2023, 11 (1) ENEURO.0102-23.2023; DOI: 10.1523/ENEURO.0102-23.2023

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Tug-of-Peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 Duplication Syndrome of Autism
Daria Bogatova, Stelios M. Smirnakis, Ganna Palagina
eNeuro 8 November 2023, 11 (1) ENEURO.0102-23.2023; DOI: 10.1523/ENEURO.0102-23.2023
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Keywords

  • autism
  • bistable perception
  • MECP2 duplication
  • visual motion perception
  • visual rivalry

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