Limitations of the Hodgkin-Huxley formalism : effects of single channel kinetics on transmembrane voltage dynamics

A standard membrane model, based on the continuous deterministic Hodgkin-Huxley equations, is compared to an alternative membrane model, based on discrete stochastic ion channel populations represented through Marlcov processes. Simulations explore the relationship between these two levels of description: the behavior predicted by the macroscopic membrane currents versus the behavior predicted by their microscopic ion channels. Discussion considers the extent to which these random events underlying neural signals mediate random events in neural computation

Stochastic resonance as a collective property of ion channel assemblies

By use of a stochastic generalization of the Hodgkin-Huxley model we investigate both the phenomena of stochastic resonance (SR) and coherence resonance (CR) in variable size patches of an excitable cell membrane. Our focus is on the challenge how internal noise stemming from individual ion channels does affect collective properties of the whole ensemble. We investigate both an unperturbed situation with no applied stimuli and one in which the membrane is stimulated externally by a periodic signal and additional external noise. For the nondriven case, we demonstrate the existence of an optimal size of the membrane patch for which the internal noise causes a most regular spike activity. This phenomenon shall be termed intrinsic CR. In presence of an applied periodic stimulus we demonstrate that the signal-to-noise ratio (SNR) exhibits SR vs. decreasing patch size, or vs. increasing internal noise strength, respectively. Moreover, we demonstrate that conventional SR vs. the external noise intensity occurs only for sufficiently large membrane patches, when the intensity of internal noise is below its optimal level. Thus, biological SR seemingly is rooted in the collective properties of large ion channel ensembles rather than in the individual stochastic dynamics of single ion channels.Comment: 9 pages, 2 figure

Effect of channel block on the spiking activity of excitable membranes in a stochastic Hodgkin-Huxley model

The influence of intrinsic channel noise on the spontaneous spiking activity of poisoned excitable membrane patches is studied by use of a stochastic generalization of the Hodgkin-Huxley model. Internal noise stemming from the stochastic dynamics of individual ion channels is known to affect the collective properties of the whole ion channel cluster. For example, there exists an optimal size of the membrane patch for which the internal noise alone causes a regular spontaneous generation of action potentials. In addition to varying the size of ion channel clusters, living organisms may adapt the densities of ion channels in order to optimally regulate the spontaneous spiking activity. The influence of channel block on the excitability of a membrane patch of certain size is twofold: First, a variation of ion channel densities primarily yields a change of the conductance level. Second, a down-regulation of working ion channels always increases the channel noise. While the former effect dominates in the case of sodium channel block resulting in a reduced spiking activity, the latter enhances the generation of spontaneous action potentials in the case of a tailored potassium channel blocking. Moreover, by blocking some portion of either potassium or sodium ion channels, it is possible to either increase or to decrease the regularity of the spike train.Comment: 10 pages, 3 figures, published 200

Failed back surgeries and minnesota multiphasic personality inventory (MMPI) profiles

MMPI profiles were evaluated for 105 prospective surgical patients who had previously undergone surgery or other procedures for treatment of back pain. Patients were classified into groups having undergone zero, one, two, three, or four or more previous surgeries. While all groups demonstrated a characteristic somatogenic profile, none of the MMPI validity or clinical scales significantly differentiated the groups and there was no relationship between increased number of surgeries and MMPI scale characteristics. These results support the nonoptimistic prognostication of the somatogenic MMPI profile for surgical intervention for back pain but show no clear relationship of MMPI profile characteristics to degree of experience of previously failed surgery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44850/1/10880_2005_Article_BF01999744.pd

Minimal state models for ionic channels involved in glucagon secretion

Pancreatic alpha cells synthesize and release glucagon. This hormone along with insulin, preserves blood glucose levels within a physiological range. During low glucose levels, alpha cells exhibit electrical activity related to glucagon secretion. In this paper, we introduce minimal state models for those ionic channels involved in this electrical activity in mice alpha cells. For estimation of model parameters, we use Monte Carlo algorithms to fit steadystate channel currents. Then, we simulate dynamic ionic currents following experimental protocols. Our aims are 1) To understand the individual ionic channel functioning and modulation that could affect glucagon secretion, and 2) To simulate ionic currents actually measured in voltage-clamp alpha-cell experiments in mice. Our estimations indicate that alpha cells are highly permeable to sodium and potassium which mainly manage action potentials. We have also found that our estimated N-type calcium channel population and density in alpha cells is in good agreement to those reported for L-type calcium channels in beta cells. This finding is strongly relevant since both, L-type and N-type calcium channels, play a main role in insulin and glucagon secretion, respectively

Perceptions of Problem Behavior in Adolescents’ Families: Perceiver, Target, and Family Effects

Considerable research has focused on the reliability and validity of informant reports of family behavior, especially maternal reports of adolescent problem behavior. None of these studies, however, has based their orientation on a theoretical model of interpersonal perception. In this study we used the social relations model (SRM) to examine family members’ reports of each others’ externalizing and internalizing problem behavior. Two parents and two adolescents in 69 families rated each others’ behavior within a round-robin design. SRM analysis showed that within-family perceptions of externalizing and internalizing behaviors are consistently due to three sources of variance; perceiver, target, and family effects. A family/contextual effect on informant reports of problem behavior has not been previously reported

Male bisexual arousal: A matter of curiosity?

Conflicting evidence exists regarding whether bisexual-identified men are sexually aroused to both men and women. We hypothesized that a distinct characteristic, level of curiosity about sexually diverse acts, distinguishes bisexual-identified men with and without bisexual arousal. Study 1 assessed men's (n = 277) sexual arousal via pupil dilation to male and female sexual stimuli. Bisexual men were, on average, higher in their sexual curiosity than other men. Despite this general difference, only bisexual-identified men with elevated sexual curiosity showed bisexual arousal. Those lower in curiosity had responses resembling those of homosexual men. Study 2 assessed men's (n = 72) sexual arousal via genital responses and replicated findings of Study 1. Study 3 provided information on the validity on our measure of sexual curiosity by relating it to general curiosity and sexual sensation seeking (n = 83). Based on their sexual arousal and personality, at least two groups of men identify as bisexual

Constantly connected – The effects of smart-devices on mental health

A number of studies have demonstrated the mental health implications of excessive Internet-browsing, gaming, texting, emailing, social networking, and phone calling. However, no study to date has investigated the impact of being able to conduct all of these activities on one device. A smart-device (i.e., smart-phone or tablet) allows these activities to be conducted anytime and anywhere, with unknown mental health repercussions. This study investigated the association between smart-device use, smart-device involvement and mental health. Two-hundred and seventy-four participants completed an online survey comprising demographic questions, questions concerning smart-device use, the Mobile Phone Involvement Questionnaire, the Internet Addiction Test and the Depression, Anxiety and Stress Scales. Higher smart-device involvement was significantly associated with higher levels of depression and stress but not anxiety. However, smart-device use was not significantly associated with depression, anxiety or stress. These findings suggest that it is the nature of the relationship a person has with their smart-device that is predictive of depression and stress, rather than the extent of use

Pupil Dilation to Explicit and Non-Explicit Sexual Stimuli

Pupil dilation to explicit sexual stimuli (footage of naked and aroused men or women) can elicit sex and sexual orientation differences in sexual response. If similar patterns were replicated with non-explicit sexual stimuli (footage of dressed men and women), then pupil dilation could be indicative of automatic sexual response in fully noninvasive designs. We examined this in 325 men and women with varied sexual orientations to determine whether dilation patterns to non-explicit sexual stimuli resembled those to explicit sexual stimuli depicting the same sex or other sex. Sexual orientation differences in pupil dilation to non-explicit sexual stimuli mirrored those to explicit sexual stimuli. However, the relationship of dilation to non-explicit sexual stimuli with dilation to corresponding explicit sexual stimuli was modest, and effect magnitudes were smaller with non-explicit sexual stimuli than explicit sexual stimuli. The prediction that sexual orientation differences in pupil dilation are larger in men than in women was confirmed with explicit sexual stimuli but not with non-explicit sexual stimuli

Chromosome microarray analysis as first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities

n this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors