Dataset Information

Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

ABSTRACT: Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across participants, sensorimotor processing at pursuit initiation was significantly associated with a single nucleotide polymorphism in IPO8 (12p11.21, P=8 × 10-11), whereas suggestive associations with sustained pursuit maintenance were identified with SNPs in SH3GL2 (9p22.2, P=3 × 10-8). In participants of predominantly African ancestry, sensorimotor processing was also significantly associated with SNPs in PCDH12 (5q31.3, P=1.6 × 10-10), and suggestive associations were observed with NRSN1 (6p22.3, P=5.4 × 10-8) and LMO7 (13q22.2, P=7.3x10-8), whereas antisaccade error rate was significantly associated with a non-coding region at chromosome 7 (P=6.5 × 10-9). Exploratory pathway analyses revealed associations with nervous system development and function for 40 top genes with sensorimotor processing and pursuit maintenance (P=4.9 × 10-2-9.8 × 10-4). Our findings suggest novel patterns of genetic variation relevant for brain systems subserving eye movement control known to be impaired in psychotic disorders. They include genes involved in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous system development and function.

SUBMITTER: Lencer R

PROVIDER: S-EPMC5682604 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

Lencer R R Mills L J LJ Alliey-Rodriguez N N Shafee R R Lee A M AM Reilly J L JL Sprenger A A McDowell J E JE McCarroll S A SA Keshavan M S MS Pearlson G D GD Tamminga C A CA Clementz B A BA Gershon E S ES Sweeney J A JA Bishop J R JR

Translational psychiatry 20171024 10

Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in ...[more]

PMID: 29064472

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Project description:Smooth pursuit eye movements (pursuit) are used to minimize the retinal motion of moving objects. During pursuit, the pattern of motion on the retina carries not only information about the object movement but also reafferent information about the eye movement itself. The latter arises from the retinal flow of the stationary world in the direction opposite to the eye movement. To extract the global direction of motion of the tracked object and stationary world, the visual system needs to integrate ambiguous local motion measurements (i.e., the aperture problem). Unlike the tracked object, the stationary world's global motion is entirely determined by the eye movement and thus can be approximately derived from motor commands sent to the eye (i.e., from an efference copy). Because retinal motion opposite to the eye movement is dominant during pursuit, different motion integration mechanisms might be used for retinal motion in the same direction and opposite to pursuit. To investigate motion integration during pursuit, we tested direction discrimination of a brief change in global object motion. The global motion stimulus was a circular array of small static apertures within which one-dimensional gratings moved. We found increased coherence thresholds and a qualitatively different reflexive ocular tracking for global motion opposite to pursuit. Both effects suggest reduced sampling of motion opposite to pursuit, which results in an impaired ability to extract coherence in motion signals in the reafferent direction. We suggest that anisotropic motion integration is an adaptation to asymmetric retinal motion patterns experienced during pursuit eye movements. NEW & NOTEWORTHY This study provides a new understanding of how the visual system achieves coherent perception of an object's motion while the eyes themselves are moving. The visual system integrates local motion measurements to create a coherent percept of object motion. An analysis of perceptual judgments and reflexive eye movements to a brief change in an object's global motion confirms that the visual and oculomotor systems pick fewer samples to extract global motion opposite to the eye movement.

Project description:Smooth pursuit and motion perception have mainly been investigated with stimuli moving along linear trajectories. Here we studied the quality of pursuit movements to curved motion trajectories in human observers and examined whether the pursuit responses would be sensitive enough to discriminate various degrees of curvature. In a two-interval forced-choice task subjects pursued a Gaussian blob moving along a curved trajectory and then indicated in which interval the curve was flatter. We also measured discrimination thresholds for the same curvatures during fixation. Motion curvature had some specific effects on smooth pursuit properties: trajectories with larger amounts of curvature elicited lower open-loop acceleration, lower pursuit gain, and larger catch-up saccades compared with less curved trajectories. Initially, target motion curvatures were underestimated; however, ∼300 ms after pursuit onset pursuit responses closely matched the actual curved trajectory. We calculated perceptual thresholds for curvature discrimination, which were on the order of 1.5 degrees of visual angle (°) for a 7.9° curvature standard. Oculometric sensitivity to curvature discrimination based on the whole pursuit trajectory was quite similar to perceptual performance. Oculometric thresholds based on smaller time windows were higher. Thus smooth pursuit can quite accurately follow moving targets with curved trajectories, but temporal integration over longer periods is necessary to reach perceptual thresholds for curvature discrimination.NEW & NOTEWORTHY Even though motion trajectories in the real world are frequently curved, most studies of smooth pursuit and motion perception have investigated linear motion. We show that pursuit initially underestimates the curvature of target motion and is able to reproduce the target curvature ∼300 ms after pursuit onset. Temporal integration of target motion over longer periods is necessary for pursuit to reach the level of precision found in perceptual discrimination of curvature.

Dataset Information

Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

Publications

Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

Similar Datasets

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