Lithium Decreases Glial Fibrillary Acidic Protein in a Mouse Model of Alexander Disease.

Alexander disease is a fatal neurodegenerative disease caused by mutations in the astrocyte intermediate filament glial fibrillary acidic protein (GFAP). The disease is characterized by elevated levels of GFAP and the formation of protein aggregates, known as Rosenthal fibers, within astrocytes. Lithium has previously been shown to decrease protein aggregates by increasing the autophagy pathway for protein degradation. In addition, lithium has also been reported to decrease activation of the transcription factor STAT3, which is a regulator of GFAP transcription and astrogliogenesis. Here we tested whether lithium treatment would decrease levels of GFAP in a mouse model of Alexander disease. Mice with the Gfap-R236H point mutation were fed lithium food pellets for 4 to 8 weeks. Four weeks of treatment with LiCl at 0.5% in food pellets decreased GFAP protein and transcripts in several brain regions, although with mild side effects and some mortality. Extending the duration of treatment to 8 weeks resulted in higher mortality, and again with a decrease in GFAP in the surviving animals. Indicators of autophagy, such as LC3, were not increased, suggesting that lithium may decrease levels of GFAP through other pathways. Lithium reduced the levels of phosphorylated STAT3, suggesting this as one pathway mediating the effects on GFAP. In conclusion, lithium has the potential to decrease GFAP levels in Alexander disease, but with a narrow therapeutic window separating efficacy and toxicity

Gender Monstrosity

Deadgirl (2008) is based around a group of male teens discovering and claiming ownership of a bound female zombie, using her as a sex slave. This narrative premise raises numerous tensions that are particularly amplified by using a zombie as the film’s central victim. The Deadgirl is sexually passive yet monstrous, reifying the horrors associated with the female body in patriarchal discourses. She is objectified on the basis of her gender, and this has led many reviewers to dismiss the film as misogynistic Torture Porn. However, the conditions under which masculinity is formed here – where adolescent males become "men" by enacting sexual violence – are as problematic as the specter of the female zombie. Deadgirl is clearly horrific and provocative: in this article I seek to probe implications arising from the film’s gender conflicts

Temporal Processing in Low-Frequency Channels: Effects of Age and Hearing Loss in Middle-Aged Listeners

Background: Hearing loss and age interfere with the auditory system\u27s ability to process temporal changes in the acoustic signal. A key unresolved question is whether high-frequency sensorineural hearing loss (HFSNHL) affects temporal processing in the low-frequency region where hearing loss is minimal or nonexistent. A second unresolved question is whether changes in hearing occur in middle-aged subjects in the absence of HFSNHL. Purpose: The purpose of this study was twofold: (1) to examine the influence of HFSNHL and aging on the auditory temporal processing abilities of low-frequency auditory channels with normal hearing sensitivity and (2) to examine the relations among gap detection measures, self-assessment reports of understanding speech, and functional measures of speech perception in middle-aged individuals with and without HFSNHL. Research Design: The subject groups were matched for either age (middle age) or pure-tone sensitivity (with or without hearing loss) to study the effects of age and HFSNHL on behavioral and functional measures of temporal processing and word recognition performance. These effects were analyzed by individual repeated-measures analyses of variance. Post hoc analyses were performed for each significant main effect and interaction. The relationships among the measures were analyzed with Pearson correlations. Study Sample: Eleven normal-hearing young adults (YNH), eight normal-hearing middle-aged adults (MANH), and nine middle-aged adults with HFSNHL were recruited for this study. Normal hearing sensitivity was defined as pure-tone thresholds ≤25 dB HL for octave frequencies from 250 to 8000 Hz. HFSNHL was defined as pure-tone thresholds ≤25 dB HL from 250 to 2000 Hz and ≥35 dB HL from 3000 to 8000 Hz. Data Collection and Analysis: Gap detection thresholds (GDTs) were measured under within-channel and between-channel conditions with the stimulus spectrum limited to regions of normal hearing sensitivity for the HFSNHL group (i.e., \u3c2000 \u3eHz). Self-perceived hearing problems were measured by a questionnaire (Abbreviated Profile of Hearing Aid Benefit), and word recognition performance was assessed under four conditions: quiet and babble, with and without low-pass filtering (cutoff frequency = 2000 Hz). Results: The effects of HFSNHL and age were found for gap detection, self-perceived hearing problems, and word recognition in noise. The presence of HFSNHL significantly increased GDTs for stimuli presented in regions of normal pure-tone sensitivity. In addition, middle-aged subjects with normal hearing sensitivity reported significantly more problems hearing in background noise than the young normal-hearing subjects. Significant relationships between self-report measures of hearing ability in background noise and word recognition in babble were found. Conclusions: The conclusions from the present study are twofold: (1) HFSNHL may have an off-channel impact on auditory temporal processing, and (2) presenescent changes in the auditory system of MANH subjects increased self-perceived problems hearing in background noise and decreased functional performance in background noise compared with YNH subjects

Amplitude-Modulated Auditory Steady-State Responses in Younger and Older Listeners

The primary purpose of this investigation was to determine whether temporal coding in the auditory system was the same for younger and older listeners. Temporal coding was assessed by amplitude-modulated auditory steady-state responses (AM ASSRs) as a physiologic measure of phase-locking capability. The secondary purpose of this study was to determine whether AM ASSRs were related to behavioral speech understanding ability. AM ASSRs showed that the ability of the auditory system to phase lock to a temporally altered signal is dependent on modulation rate, carrier frequency, and age of the listener. Specifically, the interaction of frequency and age showed that younger listeners had more phase locking than old listeners at 500 Hz. The number of phase-locked responses for the 500 Hz carrier frequency was significantly correlated to word-recognition performance. In conclusion, the effect of aging on temporal processing, as measured by phase locking with AM ASSRs, was found for low-frequency stimuli where phase locking in the auditory system should be optimal. The exploration, and use, of electrophysiologic responses to measure auditory timing analysis in humans has the potential to facilitate the understanding of speech perception difficulties in older listeners

Auditory Steady State Responses Recorded in Multitalker Babble

Objective: The primary purpose of this investigation was to determine the effect of multitalker babble on ASSRs in adult subjects with normal hearing (NH) and sensorineural hearing loss (HI). The secondary purpose was to investigate the relationships among ASSRs, word recognition in quiet, and word recognition in babble. Design: ASSRs were elicited by a complex mixed-modulation tonal stimulus (carrier frequencies of 500, 1500, 2500, and 4000 Hz; modulation rate of 40 or 90 Hz) presented in quiet and in babble. The level of each carrier frequency was adjusted to match the level of the multitalker babble spectrum, which was based on the long term speech spectrum average. Word recognition in noise (WIN) performance was measured and correlated to ASSR amplitude and ASSR detection rate. Study Sample: Nineteen normal-hearing adults and nineteen adults with sensorineural hearing loss were recruited. Results and Conclusions: The presence of babble significantly reduced the ASSR detection rate and ASSR amplitude for NH subjects, but had minimal effect on ASSRs for HI subjects. In addition, babble enhanced ASSR amplitude at high stimulus levels. ASSR detection rate and ASSR amplitude recorded in quiet and babble were significantly correlated with word recognition performance for NH and HI subjects. Sumario Objetivo: El objetivo fundamental de esta investigación fue determinar el efecto de balbuceo de hablantes múltiples en los ASSR de adultos jóvenes con audición normal (NH) y con pérdidas auditivas sensorineurales (HI). El objetivo secundario fue investigar las relaciones entre los ASSR, el reconocimiento de palabras en silencio y el reconocimiento de palabras con en medio de balbuceo. Diseño: Los ASSR fueron evocados por estímulo tonal de modulación mezclada compleja (frecuencias portadoras de 500, 1500, 2500 y 4000 Hz; tasa de modulación de 40 o 90 Hz) presentadas en silencio y con el balbuceo. Se ajustó el nivel de cada frecuencia portadora para emparejar el nivel del espectro del balbuceo de hablantes múltiples, el cual se basó en el promedio del espectro a largo plazo. Se midió el rendimiento para el reconocimiento de palabras en ruido (WIN) y se correlacionó con la amplitud de los ASSR y con la tasa de detección de los ASSR. Muestra Del Estudio: Se reclutaron diez y nueve adultos normoyentes y diez y nueve adultos con pérdida auditiva sensorineural. Resultados Y Conclusiones: La presencia del balbuceo reduce significativamente la tasa de detección de los ASSR y la amplitud de los ASSR en sujetos NH, pero tiene efectos mínimos en los ASSR de sujetos HI. Además, el balbuceo aumenta la amplitud de los ASSR con estímulos de niveles altos. La tasa de detección de los ASSR y la amplitud de los ASSR registrada en silencio y con balbuceo, fueron significativamente correlacionadas con el rendimiento para reconocer palabras en sujetos NH y HI

Behavioral and Electrophysiologic Binaural Processing in Persons With Symmetric Hearing Loss

Background: Binaural hearing improves our ability to understand speech and to localize sounds. Hearing loss can interfere with binaural cues, and despite the success of amplification, ∼25% of people with bilateral hearing loss fit with two hearing aids choose to wear only one (e.g., Brooks and Bulmer, 1981). One explanation is reduced binaural processing, which occurs when the signal presented to one ear interferes with the perception of the signal presented to the other ear (e.g., Jerger et al, 1993). Typical clinical measures, however, are insensitive to binaural processing deficits. Purpose: The purpose of this study was to determine the extent to which behavioral measures of binaural performance were related to electrophysiological measures of binaural processing in subjects with symmetrical pure-tone sensitivity. Research Design: The relationship between middle latency responses (MLRs) and behavioral performance on binaural listening tasks was assessed by Spearman\u27s rho correlation analyses. Separate repeated measures analyses of variance (RMANOVAs) were performed for MLR latency and MLR amplitude. Study Sample: Nineteen subjects were recruited for the present study based on a clinical presentation of symmetrical pure-tone sensitivity with asymmetrical performance on a word-recognition in noise test. This subpopulation of patients included both subjects with and subjects without hearing loss. Data Collection and Analysis: Monaural and binaural auditory processing was measured behaviorally and electrophysiologically in right-handed subjects. The behavioral tests included the Words-in-Noise test (WIN), the dichotic digits test (DDT), and the 500 Hz masking level difference (MLD). Electrophysiologic responses were measured by the binaural interaction component (BIC) of the MLR. The electrophysiological responses were analyzed to examine the effects of peak (Na, Pa, and Nb) and condition (monaural left, monaural right, binaural, and BIC) on MLR amplitude and latency. Results: Significant correlations were found among electrophysiological measures of binaural hearing and behavioral tests of binaural hearing. A strong correlation between the MLD and the binaural Na-Pa amplitude was found (r =.816). Conclusions: The behavioral and electrophysiological measures used in the present study clearly showed evidence of reduced binaural processing in ∼10 of the subjects in the present study who had symmetrical pure-tone sensitivity. These results underscore the importance of understanding binauralauditory processing and how these measures may or may not identify functional auditory problems