Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3,4,5,6. Increased neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci3,4. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; rg = 0.69, s.e. = 0.07) and subjective well-being (rg = –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD

FMRI of optokinetic eye movements with and without a contribution of smooth pursuit

BACKGROUND AND PURPOSE Optokinetic eye movements are elicited when tracking a moving pattern. It can be argued that a moving pattern of stripes invokes both the optokinetic and the smooth pursuit eye movement system, which may confound the observed brain activation patterns using functional magnetic resonance imaging (fMRI). A moving pattern of limited-lifetime-dot stimulation does not target the smooth pursuit eye movement system. METHODS fMRI was used to compare the cortical activity elicited by an optokinetic eye movement response evoked by a moving pattern of stripes and a moving pattern of limited lifetime dots. RESULTS The eye movement behavior showed that both types of stimuli evoked an adequate and similar optokinetic eye movement response, but stimulation with stripes evoked more activation in the frontal and parietal eye fields, MT/V5, and in the cerebellar area VI than stimulation with limited-lifetime dots. CONCLUSIONS These brain areas are implicated in smooth pursuit eye movements. Our results suggest that indeed both the optokinetic and the smooth pursuit eye movement system are involved in tracking a moving pattern of stripes

Differences between smooth pursuit and optokinetic eye movements using limited lifetime dot stimulation: a functional magnetic resonance imaging study

In this study, we examined possible differences in brain activation between smooth pursuit and optokinetic reflexive (OKR) eye movements using functional magnetic resonance imaging (fMRI). Eighteen healthy subjects performed two different eye movement paradigms. In the first paradigm, smooth pursuit eye movements were evoked by a single moving dot. In the second paradigm, optokinetic eye movements without a foveal smooth pursuit component were evoked by a moving pattern of multiple dots with a limited lifetime. As expected, the two eye movement systems show overlapping pathways, but the direct comparison of the activation patterns between the two experiments showed that the frontal eye field, MT/V5 and cerebellar area VI appear to be more activated during smooth pursuit than during optokinetic eye movements. These results showed that the smooth pursuit and optokinetic eye movement systems can be differentiated with fMRI using limited lifetime dots as an effective OKR stimulus

Cerebellar Contributions to the Processing of Saccadic Errors

Saccades are fast eye movements that direct the point of regard to a target in the visual field. Repeated post-saccadic visual errors can induce modifications of the amplitude of these saccades, a process known as saccadic adaptation. Two experiments using the same paradigm were performed to study the involvement of the cerebrum and the cerebellum in the processing of saccadic errors using functional magnetic resonance imaging and in-scanner eye movement recordings. In the first active condition, saccadic adaptation was prevented using a condition in which the saccadic target was shifted to a variable position during the saccade towards it. This condition induced random saccadic errors as opposed to the second active condition in which the saccadic target was not shifted. In the baseline condition, subjects looked at a stationary dot. Both active conditions compared with baseline evoked activation in the expected saccade-related regions using a stringent statistical threshold [the frontal and parietal eye fields, primary visual area, MT/V5, and the precuneus (V6) in the cerebrum; vermis VI-VII; and lobule VI in the cerebellum, known as the oculomotor vermis). In the direct comparison between the two active conditions, significantly more cerebellar activation (vermis VIII, lobules VIII-X, left lobule VIIb) was observed with random saccadic errors (using a more relaxed statistical threshold). These results suggest a possible role for areas outside the oculomotor vermis of the cerebellum in the processing of saccadic errors. Future studies of these areas with, e.g., electrophysiological recordings, may reveal the nature of the error signals that drive the amplitude modification of saccadic eye movements