Visual fixation and continuous head rotations have minimal effect on set-point adaptation to magnetic vestibular stimulation

Background: Strong static magnetic fields such as those in an MRI machine can induce sensations of self-motion and nystagmus. The proposed mechanism is a Lorentz force resulting from the interaction between strong static magnetic fields and ionic currents in the inner ear endolymph that causes displacement of the semicircular canal cupulae. Nystagmus persists throughout an individual's exposure to the magnetic field, though its slow-phase velocity partially declines due to adaptation. After leaving the magnetic field an after effect occurs in which the nystagmus and sensations of rotation reverse direction, reflecting the adaptation that occurred while inside the MRI. However, the effects of visual fixation and of head shaking on this early type of vestibular adaptation are unknown. Methods: Three-dimensional infrared video-oculography was performed in six individuals just before, during (5, 20, or 60 min) and after (4, 15, or 20 min) lying supine inside a 7T MRI scanner. Trials began by entering the magnetic field in darkness followed 60 s later, either by light with visual fixation and head still, or by continuous yaw head rotations (2 Hz) in either darkness or light with visual fixation. Subjects were always placed in darkness 10 or 30 s before exiting the bore. In control conditions subjects remained in the dark with the head still for the entire duration. Results: In darkness with head still all subjects developed horizontal nystagmus inside the magnetic field, with slow-phase velocity partially decreasing over time. An after effect followed on exiting the magnet, with nystagmus in the opposite direction. Nystagmus was suppressed during visual fixation; however, after resuming darkness just before exiting the magnet, nystagmus returned with velocity close to the control condition and with a comparable after effect. Similar after effects occurred with continuous yaw head rotations while in the scanner whether in darkness or light. Conclusions: Visual fixation and sustained head shaking either in the dark or with fixation inside a strong static magnetic field have minimal impact on the short-term mechanisms that attempt to null unwanted spontaneous nystagmus when the head is still, so called VOR set-point adaptation. This contrasts with the critical influence of vision and slippage of images on the retina on the dynamic (gain and direction) components of VOR adaptation

Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein.

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes

Visual fixation and continuous head rotations have minimal effect on set-point adaptation to magnetic vestibular stimulation

Background: Strong static magnetic fields such as those in an MRI machine can induce sensations of self-motion and nystagmus. The proposed mechanism is a Lorentz force resulting from the interaction between strong static magnetic fields and ionic currents in the inner ear endolymph that causes displacement of the semicircular canal cupulae. Nystagmus persists throughout an individual's exposure to the magnetic field, though its slow-phase velocity partially declines due to adaptation. After leaving the magnetic field an after effect occurs in which the nystagmus and sensations of rotation reverse direction, reflecting the adaptation that occurred while inside the MRI. However, the effects of visual fixation and of head shaking on this early type of vestibular adaptation are unknown. Methods: Three-dimensional infrared video-oculography was performed in six individuals just before, during (5, 20, or 60 min) and after (4, 15, or 20 min) lying supine inside a 7T MRI scanner. Trials began by entering the magnetic field in darkness followed 60 s later, either by light with visual fixation and head still, or by continuous yaw head rotations (2 Hz) in either darkness or light with visual fixation. Subjects were always placed in darkness 10 or 30 s before exiting the bore. In control conditions subjects remained in the dark with the head still for the entire duration. Results: In darkness with head still all subjects developed horizontal nystagmus inside the magnetic field, with slow-phase velocity partially decreasing over time. An after effect followed on exiting the magnet, with nystagmus in the opposite direction. Nystagmus was suppressed during visual fixation; however, after resuming darkness just before exiting the magnet, nystagmus returned with velocity close to the control condition and with a comparable after effect. Similar after effects occurred with continuous yaw head rotations while in the scanner whether in darkness or light. Conclusions: Visual fixation and sustained head shaking either in the dark or with fixation inside a strong static magnetic field have minimal impact on the short-term mechanisms that attempt to null unwanted spontaneous nystagmus when the head is still, so called VOR set-point adaptation. This contrasts with the critical influence of vision and slippage of images on the retina on the dynamic (gain and direction) components of VOR adaptation

Classification of vestibular signs and examination techniques: Nystagmus and nystagmus-like movements

This paper presents a classification and definitions for types of nystagmus and other oscillatory eye movements relevant to evaluation of patients with vestibular and neurological disorders, formulated by the Classification Committee of the Bar´ any Society, to facilitate identification and communication for research and clinical care. Terminology surrounding the ´ numerous attributes and influencing factors necessary to characterize nystagmus are outlined and defined. The classification first organizes the complex nomenclature of nystagmus around phenomenology, while also considering knowledge of anatomy, pathophysiology, and etiology. Nystagmus is distinguished from various other nystagmus-like movements including saccadic intrusions and oscillations

Frontotemporal dementia and its subtypes: A genome-wide association study

Background: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402

Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance