Spectral-temporal EEG dynamics of speech discrimination processing in infants during sleep

BACKGROUND: Oddball paradigms are frequently used to study auditory discrimination by comparing event-related potential (ERP) responses from a standard, high probability sound and to a deviant, low probability sound. Previous research has established that such paradigms, such as the mismatch response or mismatch negativity, are useful for examining auditory processes in young children and infants across various sleep and attention states. The extent to which oddball ERP responses may reflect subtle discrimination effects, such as speech discrimination, is largely unknown, especially in infants that have not yet acquired speech and language. RESULTS: Mismatch responses for three contrasts (non-speech, vowel, and consonant) were computed as a spectral-temporal probability function in 24 infants, and analyzed at the group level by a modified multidimensional scaling. Immediately following an onset gamma response (30-50 Hz), the emergence of a beta oscillation (12-30 Hz) was temporally coupled with a lower frequency theta oscillation (2-8 Hz). The spectral-temporal probability of this coupling effect relative to a subsequent theta modulation corresponds with discrimination difficulty for non-speech, vowel, and consonant contrast features. DISCUSSION: The theta modulation effect suggests that unexpected sounds are encoded as a probabilistic measure of surprise. These results support the notion that auditory discrimination is driven by the development of brain networks for predictive processing, and can be measured in infants during sleep. The results presented here have implications for the interpretation of discrimination as a probabilistic process, and may provide a basis for the development of single-subject and single-trial classification in a clinically useful context. CONCLUSION: An infant's brain is processing information about the environment and performing computations, even during sleep. These computations reflect subtle differences in acoustic feature processing that are necessary for language-learning. Results from this study suggest that brain responses to deviant sounds in an oddball paradigm follow a cascade of oscillatory modulations. This cascade begins with a gamma response that later emerges as a beta synchronization, which is temporally coupled with a theta modulation, and followed by a second, subsequent theta modulation. The difference in frequency and timing of the theta modulations appears to reflect a measure of surprise. These insights into the neurophysiological mechanisms of auditory discrimination provide a basis for exploring the clinically utility of the MM

Prevalence of optic disc haemorrhages in an elderly UK Caucasian population and possible association with reticular pseudodrusen—the Bridlington Eye Assessment Project (BEAP): a cross-sectional study (2002–2006)

Aims: To determine disc haemorrhages (DH) prevalence in an elderly UK population-the Bridlington Eye Assessment Project (BEAP).Methods: Thirty-degree (30°) fundus photographs (3549 participants ≥65 years) were graded for DH/macula changes. Glaucoma evaluation included Goldmann tonometry, 26-point suprathreshold visual-fields and mydriatic slit-lamp assessment for glaucomatous optic neuropathy.Results: 3548 participants with photographs in at least one eye. DH were present in 53 subjects (1.49%), increasing from 1.17% (65-69-year age-group) to 2.19% (80-84-year age53 group), p=0.06. DH was found in 9/96 (9.38%) right eyes (RE) with open angle glaucoma (OAG). Two of twelve RE (16.67%) with normal tension glaucoma (NTG) had DH. Prevalence in eyes without glaucoma was lower (32/3452, [0.93%]). Reticular pseudodrusen (RPD) occurred in 170/3212 (5.29%) subjects without DH, and 8/131 subjects (6.11%) with OAG. Twenty (20) eyes had normal tension glaucoma (NTG), 2 of whom had RPD (10%) (p=0.264). Within a logistic regression model, DH was associated with glaucoma (OR 10.2, 95% CI 5.32 - 19.72) and increasing age (OR 1.05, 95% CI 1.00-1.10, p=0.03). DH was associated with RPD (p=0.05) with univariate analysis but this was not statistically significant in the final adjusted model. There was no significant association with gender, diabetes mellitus (DM), hypertension treatment or AMD grade.Conclusion: DH prevalence is 1.5% in those over 65 years old and significantly associated with glaucoma and increasing age. There appears to be increased RPD prevalence in eyes with DH and NTG with age acting as a confounding factor. Larger studies are required to fully assess the relationship and investigate a possible shared aetiology of choroidal ischaemia

NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function

Reactivation of the fetal cardiac gene program is a characteristic feature of hypertrophied and failing hearts that correlates with impaired cardiac function and poor prognosis. However, the mechanism governing the reversible expression of fetal cardiac genes remains unresolved. Here we show that neuron-restrictive silencer factor (NRSF), a transcriptional repressor, selectively regulates expression of multiple fetal cardiac genes, including those for atrial natriuretic peptide, brain natriuretic peptide and α-skeletal actin, and plays a role in molecular pathways leading to the re-expression of those genes in ventricular myocytes. Moreover, transgenic mice expressing a dominant-negative mutant of NRSF in their hearts exhibit dilated cardiomyopathy, high susceptibility to arrhythmias and sudden death. We demonstrate that genes encoding two ion channels that carry the fetal cardiac currents I(f) and I(Ca,T), which are induced in these mice and are potentially responsible for both the cardiac dysfunction and the arrhythmogenesis, are regulated by NRSF. Our results indicate NRSF to be a key transcriptional regulator of the fetal cardiac gene program and suggest an important role for NRSF in maintaining normal cardiac structure and function