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Abnormal 8-Hz flicker electroretinograms in carriers of X-linked retinoschisis.

ABSTRACT: To evaluate rod-isolated, cone-isolated, and combined rod and cone flicker electroretinograms (ERGs) as a possible means to identify electrophysiological abnormalities in carriers of X-linked retinoschisis (XLRS).Full-field ERGs were recorded from six carriers of XLRS (aged 34-66 years) and eight normally sighted subjects (aged 27-59 years) under rod-isolated (ERGR), cone-isolated (ERGC), and combined rod and cone (ERGR+C) conditions. ERGs were obtained using a four-primary LED-based ganzfeld photostimulator and standard recording techniques. The four primaries were modulated sinusoidally in phase to achieve combined rod and cone activation (ERGR+C) or in different phases to achieve ERGR and ERGC by means of triple silent substitution. After 30 min of dark adaptation, 8- and 15-Hz ERGR, ERGC, and ERGR+C responses were obtained at a mean luminance level of 24 scot. cd/m(2). Standard ISCEV ERGs were also obtained from each subject.The ISCEV and 15-Hz flicker ERGs were generally within the normal range for the carriers. The 8-Hz ERGR, ERGC, and ERGR+C amplitudes were also generally normal. In contrast, the carriers had ERGR, ERGC, and ERGR+C timing abnormalities, with phase advances beyond the range of normal for the ERGR (four carriers), ERGC (four carriers), and ERGR+C (three carriers). Only one carrier had normal 8-Hz responses under all conditions.The 8-Hz ERG timing abnormalities in five of six carriers indicate that retinal function is not necessarily normal in carriers of XLRS. The 8-Hz flicker ERG may be useful for studying retinal function in these individuals.

SUBMITTER: McAnany JJ

PROVIDER: S-EPMC5556686 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Project description:Rhythmic visual stimulation ("flicker") is primarily used to "tag" processing of low-level visual and high-level cognitive phenomena. However, preliminary evidence suggests that flicker may also entrain endogenous brain oscillations, thereby modulating cognitive processes supported by those brain rhythms. Here we tested the interaction between 10 Hz flicker and endogenous alpha-band (?10 Hz) oscillations during a selective visuospatial attention task. We recorded EEG from human participants (both genders) while they performed a modified Eriksen flanker task in which distractors and targets flickered within (10 Hz) or outside (7.5 or 15 Hz) the alpha band. By using a combination of EEG source separation, time-frequency, and single-trial linear mixed-effects modeling, we demonstrate that 10 Hz flicker interfered with stimulus processing more on incongruent than congruent trials (high vs low selective attention demands). Crucially, the effect of 10 Hz flicker on task performance was predicted by the distance between 10 Hz and individual alpha peak frequency (estimated during the task). Finally, the flicker effect on task performance was more strongly predicted by EEG flicker responses during stimulus processing than during preparation for the upcoming stimulus, suggesting that 10 Hz flicker interfered more with reactive than proactive selective attention. These findings are consistent with our hypothesis that visual flicker entrained endogenous alpha-band networks, which in turn impaired task performance. Our findings also provide novel evidence for frequency-dependent exogenous modulation of cognition that is determined by the correspondence between the exogenous flicker frequency and the endogenous brain rhythms.SIGNIFICANCE STATEMENT Here we provide novel evidence that the interaction between exogenous rhythmic visual stimulation and endogenous brain rhythms can have frequency-specific behavioral effects. We show that alpha-band (10 Hz) flicker impairs stimulus processing in a selective attention task when the stimulus flicker rate matches individual alpha peak frequency. The effect of sensory flicker on task performance was stronger when selective attention demands were high, and was stronger during stimulus processing and response selection compared with the prestimulus anticipatory period. These findings provide novel evidence that frequency-specific sensory flicker affects online attentional processing, and also demonstrate that the correspondence between exogenous and endogenous rhythms is an overlooked prerequisite when testing for frequency-specific cognitive effects of flicker.

Project description:Sirtuin 1 (SIRT1) is a protein deacetylase with important cellular functions, as it regulates numerous processes, including the circadian rhythm in peripheral tissues. Efforts are ongoing to reveal how Sirt1 can be used to treat diseases, such as alcoholic liver disease (ALD), Alzheimer's disease, and liver fibrosis. We have recently shown that noninvasive exposure to 40-Hz light flicker activates hypothalamic SIRT1 gene expression, thereby regulating the central circadian clock. This study investigated the effects of 40-Hz light flicker in a mouse model of ALD. RNA sequencing (RNA-seq) analysis was performed to explore the potential pathways affected by 40-Hz light flicker. We found that 40-Hz light flicker significantly decreased the acute ethanol-induced increases in serum alanine aminotransferase (ALT) and serum triglyceride (TG) levels and reduced fat-droplet accumulation in mouse livers. Additionally, 40-Hz light flicker significantly suppressed ethanol-induced increases in sterol regulatory element binding protein 1 (SREBP-1) and fatty acid synthase (Fasn) levels. Furthermore, the ethanol induced significant decreases in both Sirt1 levels and phosphorylation of adenosine monophosphate-activated protein kinase subunit (AMPKα), compared with those in the control group. Strikingly, pretreatment with 40-Hz light flicker ameliorated such ethanol-induced decreases in SIRT1 levels and AMPKα phosphorylation. In addition, ethanol-induced increases in levels of brain and muscle arnt-like protein-1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), and period 2 (PER2) were reversed by 40-Hz light flicker. RNA-seq analysis revealed significant differences in expression of genes related to the AMPK signalling. Moreover, ethanol consumption altered mRNA levels of Sirt1 and circadian genes in the suprachiasmatic nucleus (SCN), indicating that ethanol influenced central pacemaker genes; however, 40-Hz light flicker reversed these ethanol-induced changes. Taken together, our findings demonstrate that 40-Hz light flicker rapidly influence the SCN and exhibits inhibitory properties on hepatic lipogenesis, indicating that 40-Hz light flicker has therapeutic potential for preventing alcoholic liver steatosis.

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Abnormal 8-Hz flicker electroretinograms in carriers of X-linked retinoschisis.

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