Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome

Background Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS. Methods EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0–100 Hz over 2 s. Results Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits. Conclusions This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome

(A) Scalp topographies of “local coupling”, showing correlations in each electrode between relative power of activity in the theta, and lower and upper alpha power bands and gamma power for male FXS and male healthy control participants, with significant group differences presented in the bottom row (p < 0.05, corrected), with dark blue reflecting no group difference. (B) Mean and standard error of correlations for all electrodes showing group differences as are plotted in A. * denotes correlations of spectral power in theta and upper alpha bands with gamma band power that are significantly different from zero based on the results of permutation analyses at p < 0.05. (TIF 4297 kb

Auditory EEG Biomarkers in Fragile X Syndrome: Clinical Relevance

Sensory hypersensitivities are common and distressing features of Fragile X Syndrome (FXS). While there are many drug interventions that reduce behavioral deficits in Fmr1 mice and efforts to translate these preclinical breakthroughs into clinical trials for FXS, evidence-based clinical interventions are almost non-existent potentially due to lack of valid neural biomarkers. Local circuit function in sensory networks is dependent on the dynamic balance of activity in inhibitory/excitatory synapses. Studies are needed to examine the association of electrophysiological alterations in neural systems with sensory and other clinical features of FXS to establish their clinical relevance. Adolescents and adults with FXS (n = 38, Mean age = 25.5, std = 10.1; 13 females) and age matched typically developing controls (n = 40, Mean age = 27.7, std = 12.1; 17 females) completed auditory chirp and auditory habituation tasks while undergoing dense array electroencephalography (EEG). Amplitude, latency, and percent change (habituation) in N1 and P2 event-related potential (ERP) components were characterized for the habituation task; time-frequency calculations using Morlet wavelets characterized phase-locking and single trial power for the habituation and chirp tasks. FXS patients showed increased amplitude but some evidence for reduced habituation of the N1 ERP, and reduced phase-locking in the low and high gamma frequency range and increased low gamma power to the chirp stimulus. FXS showed increased theta power in both tasks. While the habituation finding was weaker than previously found, the remaining findings replicate our previous work in a new sample of patients with FXS. Females showed less deficit in the chirp task but not the habituation task. Abnormal increases in gamma power were related to more severe behavioral and psychiatric features as well as reductions in neurocognitive abilities. Replicating electrophysiological deficits in a new group of patients using different EEG equipment at a new data collection site with differing levels of environmental noise that were robust to data processing techniques utilizing multiple researchers, indicates a potential for scalability to multi-site clinical trials. Given the robust replicability, relevance to clinical measures, and preclinical evidence for sensitivity of these EEG measures to pharmacological intervention, the observed abnormalities may provide novel translational markers of target engagement and potentially outcome measures in large-scale studies evaluating new treatments targeting neural hyperexcitability in FXS.This study was supported by NIMH/NICHD grant U54 HD082008-01 (Huber and JS). Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Electrophysiological assessment methodology of sensory processing dysfunction in schizophrenia and dementia of the Alzheimer type

Schizophrenia and Alzheimer’s disease impacts on various sensory processings are extensively reviewed in the present publication. This article describes aspects of a research project whose aim is to delineate the neurobiology that may underlie Social Withdrawal in Alzheimer’s disease, Schizophrenia and Major Depression. This is a European-funded IMI 2 project, identified as PRISM (Psychiatric Ratings using Intermediate Stratified Markers). This paper focuses specifically on the selected electrophysiological paradigms chosen based on a comprehensive review of all relevant literature and practical constraints. The choice of the electrophysiological biomarkers were fundamentality based their metrics and capacity to discriminate between populations. The selected electrophysiological paradigms are resting state EEG, auditory mismatch negativity, auditory and visual based oddball paradigms, facial emotion processing ERP’s and auditory steady-state response. The primary objective is to study the effect of social withdrawal on various biomarkers and endophenotypes found altered in the target populations. This has never been studied in relationship to social withdrawal, an important component of CNS diseases

What's Queer about Political Science?

There is something queer (by which we mean strange) going on in the scholarly practice of political science. Why are political science scholars continuing to disregard issues of gender and sexuality – and in particular queer theory – in their lecture theatres, seminar rooms, textbooks, and journal articles? Such everyday issues around common human experience are considered by other social scientists to be central to the practice and theory of social relations. In this article we discuss how these commonplace issues are being written out of (or, more accurately, have never been written in to) contemporary political science. First, we present and discuss our findings on citation practice in order to evidence the queerness of what does and does not get cited in political science scholarship. We then go on to critique this practice before suggesting a broader agenda for the analysis of the political based on a queer theoretical approach

Economic Returns from Treating Sand Shinnery Oak with Tebuthiuron in West Texas

Net returns from control of sand shinnery oak (Quercus havardii) with tebuthiuron [N-(5-1,1-dimethylethyl 1,3,4,-thiadiazol-2-yl)-N, N′-dimethylurea] were evaluated for Southern High Plains ranges. A forage yield function was estimated with regression using 5 years of herbage yield data from the region. The present value of production was determined for 3 calf prices, 3 discount rates, and 4 tebuthiuron treatment rates. Discounted net returns were generally positive with high and moderate calf prices and low and moderate discount rates. The optimum tebuthiuron treatment rate varies with calf prices, discount rate, and treatment cost.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

Health Insurance Knowledge Among Medicare Beneficiaries

OBJECTIVE: To assess the effect of new consumer information materials about the Medicare program on beneficiary knowledge of their health care coverage under the Medicare system. DATA SOURCE: A telephone survey of 2,107 Medicare beneficiaries in the 10-county Kansas City metropolitan statistical area. STUDY DESIGN: Beneficiaries were randomly assigned to a control group and three treatment groups each receiving a different set of Medicare informational materials. The “handbook-only” group received the Health Care Financing Administration's new Medicare & You 1999 handbook. The “bulletin” group received an abbreviated version of the handbook, and the “handbook + CAHPS” group received the Medicare & You handbook plus the Consumer Assessment of Health Plans (CAHPS)(®) survey report comparing the quality of health care provided by Medicare HMOs. Beneficiaries interested in receiving information were oversampled. DATA COLLECTION METHODS: Data were collected during two separate telephone surveys of Medicare beneficiaries: one survey of new beneficiaries and another survey of experienced beneficiaries. The intervention materials were mailed to sample members in advance of the interviews. Knowledge for the treatment groups was measured shortly after beneficiaries received the intervention materials. PRINCIPAL FINDINGS: Respondents' knowledge was measured using a psychometrically valid and reliable 15-item measure. Beneficiaries who received the intervention materials answered significantly more questions correctly than control group members. The effect on beneficiary knowledge of providing the information was modest for all intervention groups but varied for experienced beneficiaries only, depending on the intervention they received. CONCLUSIONS: The findings suggest that all of the new materials had a positive effect on beneficiary knowledge about Medicare and the Medicare + Choice program. While the absolute gain in knowledge was modest, it was greater than increases in knowledge associated with traditional Medicare information sources

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome

Abstract Background Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS. Methods EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0–100 Hz over 2 s. Results Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits. Conclusions This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics