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Neurophysiological correlates of response production and inhibition in alcoholics.

Scalp recordings of the P300 component of the event-related potential were made from a group of medication-free, chronic male alcoholics and a control group, participating in a visual Go/No Go reaction time paradigm. Subjects were presented with large and small forms of the letters T and V. The large forms (Go stimuli) required a button press with either the left or right hand, whereas the small forms (NO Go stimuli) required response inhibition. Recordings were made from 31 electrodes that, for statistical analyses, were grouped into five regions: frontal, central, parietal, occipital, and temporal. The results indicated that, in each of the five regions, both Go and NO Go response amplitudes were larger in the controls than in the alcoholics. No group differences in latency were observed in any region. Surface energy (Wang et al., Brain Topogr. 6:193-202, 1994) magnitudes paralleled P300 amplitudes and in the controls, compared with the alcoholics, were larger during both Go and No Go trials. Our findings suggest that abstinent, chronic alcoholics differ electro-physiologically from control individuals. These differences are manifested as widespread reductions in P300 amplitudes during the performance of a simple information processing paradigm. The reduced amplitudes may reflect a deficiency in an inhibitory mechanism proposed to underlie P300 generation.

Adult↗

Discovering distinct genes represented in 29,570 clones from infant brain cDNA libraries by applying sequencing by hybridization methodology.

To discover all distinct human genes and to determine their patterns of expression across different cell types, developmental stages, and physiological conditions, a procedure is needed for fast, mutual comparison of hundreds of thousands (and perhaps millions) of clones from cDNA libraries, as well as their comparison against data bases of sequenced DNA. In a pilot study, 29,570 clones in duplicate from both original and normalized, directional, infant brain cDNA libraries were hybridized with 107-215 heptamer oligonucleotide probes to obtain oligonucleotide sequence signatures (OSSs). The OSSs were compared and clustered based on mutual similarity into 16,741 clusters, each corresponding to a distinct cDNA. A number of distinct cDNAs were successfully recognized by matching their 107-probe OSSs against GenBank entries, indicating the possibility of sequence recognition with only a few hundred randomly chosen oligomers.

Animals↗

Diffuse panbronchiolitis in China.

OBJECTIVE: Diffuse panbronchiolitis (DPB) is a progressive inflammatory disease, well recognized in Japan, that is characterized by chronic sinusitis and obstructive small airway disease. A total of 40 patients with DPB in mainland China were reviewed in order to describe the epidemiology of DPB in China and to compare their clinical characteristics with those of cases reported in Japan. METHODOLOGY: A systematic search was conducted of the Chinese language literature published in mainland China from 1996 to 2003. The 40 subjects who fulfilled the diagnostic criteria for DPB were retrospectively analysed for clinical, physiological, radiological, and pathological features and their geographic distribution. RESULTS: The 40 patients included in this study (31 male and nine female) were distributed in 12 provinces and three other cities in China. All presented with chronic cough, sputum production, and 32 had exertional dyspnoea. All but three had a history of sinusitis. Lung function assessment showed a mixed obstructive-restrictive pattern in 30 cases. CXR revealed diffuse fine nodular shadows in all patients. Human leukocyte antigen-B54 was positive in five patients (n = 12). A total of 30 (75%) patients had been misdiagnosed prior to their diagnosis of DPB being made. CONCLUSIONS: DPB is not rare in China but its incidence is relatively low. Poor recognition and/or genetic factors may be the reason. The clinical, radiographic and histological features of Chinese patients resemble those described in Japanese patients.

Adult↗

Memory enhancement after drinking ethanol: consolidation, interference, or response bias?

One explanation for memory facilitation is that alcohol has a short-term neurochemical stimulating effect on consolidating neural networks when material is learned before drinking. Contrary to the consolidation hypothesis, when the consolidation interval was manipulated the results showed that the effects of alcohol were not time dependent. Compared to placebo subjects, alcohol significantly facilitated the recall of 25 words whether administered immediately or 40 min after learning. In addition, alcohol significantly increased the memory of words associated with pictures when incidentally learned before drinking and significantly decreased incidental learning after drinking. Another explanation for memory facilitation is that alcohol's depressive physiological effect impairs the acquisition of new information, like sleeping after learning, and enhances memory by reducing subsequent interference. Consistent with the retroactive interference hypothesis, the effects of alcohol reduced interpolated interference, were greater on recall than recognition, and were immune to time delays. Contemporary theories view memory enhancement attributed to alcohol as indirectly influencing response biases and contextual cues associated with retrieval from episodic memory.

Adult↗

Application of neural networks to pharmacodynamics.

Neural networks (NN) are computational systems implemented in software or hardware that attempt to simulate the neurological processing abilities of biological systems. A synopsis is presented of the operational characteristics, structures, and applications of NN. The NN technology has primarily been aimed at recognition science (e.g., handwriting, voice, signal, picture, image, pattern, etc.). It is pointed out that NN may also be particularly suitable to deal with pharmacokinetic (PK) and pharmacodynamic (PD) systems, especially in cases such as multivariate PK/PD population kinetics when the systems are so complex that modeling by a conventional structured model building technique is very troublesome. The main practical advantage of NN is the intrinsic ability to closely emulate virtually any multivariate system, including nonlinear systems, independently of structural/physiologic relevance. Thus, NN are most suitable to model the behavior of complex kinetic systems and unsuitable to model the structure. In a practical sense, this structure limitation may be inconsequential because NN in its multivariate formulation may consider any physiologic, clinical, or population variable that may influence the kinetic behavior. The application of NN in PD is demonstrated in terms of the ability of an NN to predict, by extrapolation, the central nervous system (CNS) activity of alfentanil. The drug was infused by a complex computer-controlled infusion scheme over 180 min with simultaneous recording of the CNS effect quantified by a fast Fourier transform power spectrum analysis. The NN was trained to recognize (emulate) the drug input-drug effect behavior of the PD system with the input-effect data for the 180 min as a training set.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗

Interleukin-2 transcription is regulated in vivo at the level of coordinated binding of both constitutive and regulated factors.

Interleukin-2 (IL-2) transcription is developmentally restricted to T cells and physiologically dependent on specific stimuli such as antigen recognition. Prior studies have shown that this stringent two-tiered regulation is mediated through a transcriptional promoter/enhancer DNA segment which is composed of diverse recognition elements. Factors binding to some of these elements are present constitutively in many cell types, while others are signal dependent, T cell specific, or both. This raises several questions about the molecular mechanism by which IL-2 expression is regulated. Is the developmental commitment of T cells reflected molecularly by stable interaction between available factors and the IL-2 enhancer prior to signal-dependent induction? At which level, factor binding to DNA or factor activity once bound, are individual regulatory elements within the native enhancer regulated? By what mechanism is developmental and physiological specificity enforced, given the participation of many relatively nonspecific elements? To answer these questions, we have used in vivo footprinting to determine and compare patterns of protein-DNA interactions at the native IL-2 locus in cell environments, including EL4 T-lymphoma cells and 32D clone 5 premast cells, which express differing subsets of IL-2 DNA-binding factors. We also used the immunosuppressant cyclosporin A as a pharmacological agent to further dissect the roles played by cyclosporin A-sensitive factors in the assembly and maintenance of protein-DNA complexes. Occupancy of all site types was observed exclusively in T cells and then only upon excitation of signal transduction pathways. This was true even though partially overlapping subsets of IL-2-binding activities were shown to be present in 32D clone 5 premast cells. This observation was especially striking in 32D cells because, upon signal stimulation, they mobilized a substantial set of IL-2 DNA-binding activities, as measured by in vitro assays using nuclear extracts. We conclude that binding activities of all classes fail to stably occupy their cognate sites in IL-2, except following activation of T cells, and that specificity of IL-2 transcription is enforced at the level of chromosomal occupancy, which appears to be an all-or-nothing phenomenon.

Animals↗

Basal plasma growth hormone levels in man: new evidence for rhythmicity of growth hormone secretion.

Circulating GH levels in man fluctuate widely due to pulsatile GH secretion by the pituitary gland. During much of the time, plasma GH is undetectable by current assays. This is punctuated by occasional secretory episodes, resulting in plasma GH peaks of varying height. The principal diurnal secretory event for GH is that associated with early slow wave sleep, but little is known about the prevailing level and dynamics of GH during the day. We used a new ultrasensitive immunoradiometric assay for GH (Boots-Celltech IRMA; limit of detection, 20 ng/L) to measure plasma GH in the previously undetectable range and to assess its diurnal pattern. Plasma GH was measured every 20 min over a 24-h period in 12 normal subjects (6 men and 6 women, aged 20-47 yr) under physiological conditions. Time series analysis of plasma GH patterns was performed by the Cluster algorithm, autocorrelation, and spectral analysis. Plasma GH, as measured by IRMA, was detectable at all time points and ranged from 40-19,695 ng/L. Dynamic fluctuations occurred within and above the previously undetectable range, with amplitudes varying over 3 orders of magnitude. Women had significantly higher overall GH levels, higher peak amplitudes, and higher valley levels/nadirs than men. GH pulses occurred with an average frequency of about 13/day in both sexes, with a dominant, but not strictly periodic, 2-h rhythmicity. We conclude that in man pulsatile GH secretion occurs throughout the day, and that it is oscillatory rather than episodic. This neurosecretory pattern has eluded recognition heretofore because of the lack of assay sensitivity. Women of reproductive age have higher pulse amplitudes and a higher baseline but equal pulse frequency compared to men. Previous estimates of integrated GH concentrations and GH production rates were too high by a factor of 2 due to overestimation of GH levels in the undetectable range.

Adult↗

Vagal tone regulation during sustained attention in boys exposed to opiates in utero.

Attention and learning problems among children exposed to opiates in utero have been previously reported but are difficult to interpret due to imprecise measurement and inadequate control of postnatal factors. In this study, we used a behavior-based measure of attention (continuous-performance tasks) and a physiological index of sustained attention (cardiac vagal tone) to measure more precisely the process of sustained attention. Boys, aged 7 to 12, exposed to opiates in utero, were compared to boys whose mothers began using illicit substances after the child's birth (environmental controls), and boys whose mothers were non-drug users. This three-group design was intended to isolate in utero effects from postnatal environmental influences. Vagal tone, a measure of heart-rate variability sensitive to vagal influences on the heart, was measured pre- and postbaseline and during the three tasks of the Gordon Diagnostic System (Delay, Vigilance, and Distractibility). Vagal tone has been found to be sensitive to changes in environmental demand for sustained attention in infants, school-age children, and adults. Results indicated that when distractors were added to the vigilance task (Distractibility task), opiate-exposed boys failed to suppress vagal tone compared to both control groups. However, both the opiate-exposed boys and the environmental controls made fewer correct responses than non-drug-exposed controls on this task. These results indicate that normal physiological responses to increased attentional demand may be impaired in boys exposed in utero to opiates in this age range. However, the poor Distractibility scores of both the opiate-exposed and environmental controls suggests an important role of environmental influences on attentional performance.

Arousal↗

Emotional-processing in posttraumatic stress disorder II: startle reflex modulation during picture processing.

This study examined the impact of a trauma-related stressor on subsequent emotional behavior in veterans with (n = 35) and without (n = 24) posttraumatic stress disorder (PTSD). Self-report and physiological responses, including acoustic startle, were recorded during viewing of emotionally evocative photographs at baseline and following exposure to trauma-related and non-trauma-related stressors. The 2 groups exhibited equivalent patterns of emotional response across self-report and physiological measures at baseline. In contrast, following the trauma challenge, participants with PTSD showed a pattern of startle modulation suggestive of greater defensive reactivity and reduced visual perceptual engagement. These findings, along with augmented corrugator EMG reactivity during the same interval, suggest that trauma-related reexperiencing primes subsequent negative emotional responding in individuals with PTSD.

Adaptation, Psychological↗

Bayesian technique for investigating linearity in event-related BOLD fMRI.

Event-related BOLD fMRI data is modeled as a linear time-invariant system. Together with Bayesian inference techniques, a statistical test is developed for rigorously detecting linearity/nonlinearity in the BOLD response system. The test is applied to data collected from eight subjects using an event-related paradigm with a switching checkerboard as the visual stimulus. Analyzed as a group, the results clearly find the response to be nonlinear. When each subject is analyzed individually, however, the results are predominantly nonlinear, but there is some evidence to suggest that there may be a crossover from a linear to a nonlinear regime and vice versa. This could be important when estimating physiological parameters for individuals. Additionally, estimates of the hemodynamic response function and corresponding response were obtained, but there was no consistent appearance of a poststimulus undershoot in the event-related BOLD response.

Adult↗

Structure-from-motion: perceptual evidence for surface interpolation.

Dynamic random-dot displays representing a rotating cylinder were used to investigate surface interpolation in the perception of structure-from-motion (SFM) in humans. Surface interpolation refers to a process in which a complete surface in depth is reconstructed from the object depth values extracted at the stimulus features. Surface interpolation will assign depth values even in parts of the object that contain no features. Such a "fill-in" process should make the detection of featureless stimulus areas ("holes") difficult. Indeed, we demonstrate that such holes in our rotating cylinder can be as wide as one-quarter of the stimulus before subjects can reliably detect their presence. Subjects were presented with a variation on the rotating cylinder in which all dots were oscillating either in synchrony or asynchronously. Subjects perceive a rigidly rotating cylinder even when such a percept is not in agreement with the physical stimulus. To reconcile this discrepancy between actual and perceived stimulus we propose that individual points contribute to a surface based object representation and that in this process the visual system looses access to the identity of the individual features that make up the surface. Finally we are able to explain a variety of previously documented perceptual peculiarities in the perception of structure-from-motion by arguing that the perceptual interpretation of the object's boundaries influences the surface interpolation process. These findings offer strong perceptual evidence for a process of surface interpolation and are also physiologically plausible given results from recordings in awake behaving monkey cortical areas V1 and MT. The companion paper demonstrates how such a surface interpolation process can be incorporated into a structure-from-motion algorithm and how object boundaries can influence the perception of structure-from-motion as has been demonstrated before and in this paper.

Depth Perception↗

Roles for inhibitory interactions in the use of the -10 promoter element by sigma 70 holoenzyme.

A panel of seven -10 region DNA mutants was tested for holoenzyme binding against a panel of 13 region 2 mutants of sigma 70. No patterns were noticed that would indicate unique interactions between individual amino acids and individual -10 region bases. Instead, certain amino acid substitutions led to increased holoenzyme binding to DNA, implying that the wild type interactions are associated with an inhibitory component. These inhibitory interactions were stronger on DNA containing non-consensus sequences, like those of typical promoters. In addition, the DNA segment downstream from the -10 element was also inhibitory to binding when in duplex form but stimulated binding when in single strand form. Overall, the data suggest that -10 region duplex recognition and melting have a large component of overcoming unfavorable protein:DNA base interactions, particularly when the bases are non-consensus, and that this contributes to setting physiologically appropriate variations in transcription rate.

Binding Sites↗

Analyzing time series gene expression data.

MOTIVATION: Time series expression experiments are an increasingly popular method for studying a wide range of biological systems. However, when analyzing these experiments researchers face many new computational challenges. Algorithms that are specifically designed for time series experiments are required so that we can take advantage of their unique features (such as the ability to infer causality from the temporal response pattern) and address the unique problems they raise (e.g. handling the different non-uniform sampling rates). RESULTS: We present a comprehensive review of the current research in time series expression data analysis. We divide the computational challenges into four analysis levels: experimental design, data analysis, pattern recognition and networks. For each of these levels, we discuss computational and biological problems at that level and point out some of the methods that have been proposed to deal with these issues. Many open problems in all these levels are discussed. This review is intended to serve as both, a point of reference for experimental biologists looking for practical solutions for analyzing their data, and a starting point for computer scientists interested in working on the computational problems related to time series expression analysis.

Adaptation, Physiological↗

Estimation of anomaly location and size using electrical impedance tomography.

We developed a new algorithm that estimates locations and sizes of anomalies in electrically conducting medium based on electrical impedance tomography (EIT) technique. When only the boundary current and voltage measurements are available, it is not practically feasible to reconstruct accurate high-resolution cross-sectional conductivity or resistivity images of a subject. In this paper, we focus our attention on the estimation of locations and sizes of anomalies with different conductivity values compared with the background tissues. We showed the performance of the algorithm from experimental results using a 32-channel EIT system and saline phantom. With about 1.73% measurement error in boundary current-voltage data, we found that the minimal size (area) of the detectable anomaly is about 0.72% of the size (area) of the phantom. Potential applications include the monitoring of impedance related physiological events and bubble detection in two-phase flow. Since this new algorithm requires neither any forward solver nor time-consuming minimization process, it is fast enough for various real-time applications in medicine and nondestructive testing.

Algorithms↗

The anatomy, physiology and functions of the perirhinal cortex.

The perirhinal cortex is a polymodal association area that contributes importantly to normal recognition memory. A convergence of recent findings from lesion and electrophysiological studies has provided new evidence that this area participates in an even broader range of memory functions than previously thought, including associative memory and emotional memory, as well as consolidation functions. These results are consistent with neuroanatomical research showing that this area has strong and reciprocal connections with widespread cortical sensory areas and with other memory-related structures, including the hippocampal formation and amygdala.

Animals↗

Sleep and its disorders.

The advances in research on sleep an biological rhythms have recently been applied to the diagnosis and treatment of sleep disorders. A new clinical specialty has developed with the establishment of sleep disorder centers and a diagnostic classification of sleep and arousal disorders. This new nosological approach has evolved from an extensive base of new scientific information concerning descriptive polygraphic and analysis of clinical case series. Four major categories have been defined: (a) disorders of initiating and maintaining sleep (insomnias), (b) disorders of excessive somnolence, (c) disorders of the sleep-wake schedule, and (d) dysfunctions associated with sleep. Within this comprehensive classification certain major pathophysiological advances are described for the "insomnias." These include polysomnographic identification of altered sleep stage patterns in the major effective illnesses, insomnias related to hypnotic drugs and alcohol, sleep disturbances associated with sleep-induced respiratory impairment, and sleep-related periodic movements during sleep (nocturnal myoclonus). Excessive daytime somnolence is primarily associated with the hypersomnia sleep-apnea syndrome and with narcolepsy. The relationship between biological rhythms (chronobiology) and disorders of the human sleep-wake schedules is very actively investigated. The recognition that sleep length, internal organization, and timing within neurophysiological circadian time-keeping systems has lead to better diagnosis of these sleep-wake disorders and new chronotherapeutic regimens. Finally, increasing identification and description of "parasomnias," i.e. dysfunctions associated with sleep, has led sleep research into important new areas that are of general physiological interest. It is now clear that sleep disorders medicine has become a new scientific and clinical discipline in its own right.

Arousal↗

Alarm communication network to help carers of the elderly for safety purposes: a survey of a project.

Over years, radical changes in engineering technology have taken place due to greatly improved instrumentation, enhanced computing power, new sensors and upgraded transmission mediums making it possible to achieve in the field what once could only be done on laboratory models. In daily life, the use of an active self-testing instrumentation endowed with a self-diagnostic capability built into the structural fabric of a machine permits us to monitor the initiation of breakdown, corrosion and erosion. This has become particularly important in such means of transportation as planes, boats and automobiles where advanced instrumentation, signal processing and pattern recognition systems operate in fairly conventional structures. By capitalizing on the technological progress in the field of instrumentation and data processing, help can be contemplated for elderly people in nursing homes through detection of abnormal situations. The continued assistance to elderly people is achieved by utilizing a technological system respectful of the elderly's privacy and operating without their active participation.

Activities of Daily Living↗

Processing of auditory information in insects.

Insects exhibit an astonishing diversity in the design of their ears and the subsequent processing of information within their auditory pathways. The aim of this review is to summarize and compare the present concepts of auditory processing by relating behavioral performance to known neuronal mechanisms. We focus on three general aspects, that is frequency, directional, and temporal processing. The first part compares the capacity (in some insects high) for frequency analysis in the ear with the rather low specificity of tuning in interneurons by looking at Q10dB values and frequency dependent inhibition of interneurons. Since sharpening of frequency does not seem to be the prime task of a set of differently tuned receptors, alternative hypotheses are discussed. Moreover, the physiological correspondence between tonotopic projections of receptors and dendritic organization of interneurons is not in all cases strong. The second part is concerned with directional hearing and thus with the ability for angular resolution of insects. The present concepts, as derived from behavioral performances, for angular resolution versus lateralization and serial versus parallel processing of directional and pattern information can be traced to the thoracic level of neuronal processing. Contralateral inhibition, a mechanism for enhancing directional tuning, appears to be most effective in parallel pathways, whereas in serial processing it may have detrimental effects on pattern processing. The third part, after some considerations of signal analysis in the temporal domain, demonstrates that closely related species often use different combinations of temporal parameters in their recognition systems. On the thoracic level, analysis of temporal modulation functions and effects of inhibition on spiking patterns reveals relatively simple processing, whereas brain neurons may exhibit more complex properties.

Acoustic Stimulation↗