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Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 37 records · Page 2Linked to original sources

Abnormal vasoreaction to arousal stimuli--an early sign of diabetic sympathetic neuropathy demonstrated by laser Doppler flowmetry.

Early diagnosis of diabetic autonomic neuropathy contributes to the prevention of serious complications and improves the prognosis of patients with diabetes. Common tests of peripheral autonomic function are the quantitative sudomotor axon reflex test or the sympathetic skin response (SSR). Quantitative sudomotor axon reflex test is quantifiable but technically demanding. Sympathetic skin response cannot be quantified easily. To study whether measurement of skin vasomotion is suited to assess early sympathetic peripheral neuropathy, we monitored skin blood flow at the index finger pulp using laser Doppler flowmetry before and after electrical stimulation. We assured that the stimulus was sufficient to elicit an efferent sympathetic response by monitoring palmar SSR ipsilateral to the flow measurement. In 21 diabetic patients with at least stage one polyneuropathy and 21 age-matched controls, SSR was recorded from one palm and sole following electrical stimulation at the contralateral wrist. Sympathetic skin response was present at the palms in all patients and controls and absent at the sole of two patients only. Eight patients (38.9%) had abnormal SSR, with absent plantar responses in two patients, prolonged plantar latencies in six patients, and prolonged volar SSR latencies in two patients. Skin blood flow responses were more often abnormal (46.1%) than SSR (P < 0.05), responses were delayed in two patients and absent in another 8 patients. Skin blood flow retest reliability was high with a repeatability coefficient of 10.64% in controls and 12.34 % in patients. Skin blood flow monitoring after sympathetic stimulation provides a reproducible parameter of sympathetic vasomotor control and complements the diagnostic value of SSR testing.

Adult↗

Conjunctions of colour, luminance and orientation: the role of colour and luminance contrast on saliency and proximity grouping in texture segregation.

To examine whether perceptual grouping on the basis of orientation can be performed simultaneously with or only subsequently to grouping according to colour or luminance, we tested whether subjects are able to segregate arrays of texture elements that differ from surrounding elements by conjunctions of either (i) colour and orientation, or (ii) luminance contrast and orientation, or (iii) luminance contrast polarity and orientation. Subjects were able to use conjunctions between luminance and orientation for segregation but not conjunctions between colour or contrast polarity and orientation. Our results suggest that (i) in agreement with earlier findings, there seem to exist no specific conjunction detectors for colour and orientation or contrast polarity and orientation, and (ii) when orientation defined textures are to be distinguished by virtue of differences in luminance, colour, or contrast polarity, luminance provides a much stronger cue than colour or contrast polarity for saliency-based orientation grouping.

Adaptation, Ocular↗

Effect of soluble and insoluble fiber diets on serum prostate specific antigen in men.

PURPOSE: We assess whether high fiber diets influence serum prostate specific antigen (PSA) related to effects on serum sex hormone levels and fecal steroid excretion. MATERIALS AND METHODS: A randomized crossover controlled trial was performed on 14 healthy men with hyperlipidemia on 2 metabolic diets 4 months in duration with each containing foods high in soluble or insoluble fiber and approximately 25 to 30 gm. dietary fiber per 1,000 kilocalories. Serum PSA, free testosterone and estradiol, and fecal bile acid and neutral sterol excretion were evaluated. RESULTS: Mean serum PSA was lower with the soluble than the insoluble fiber diet (0.07+/-0.03 ng./ml., p = 0.035). No treatment difference was seen in free testosterone or estradiol, although the latter decreased significantly with the insoluble fiber diet (9+/-3 pmol./l., p = 0.004). After 16 weeks total fecal bile acid output was greater with the soluble (341+/-56 mg. daily) compared to the insoluble (203+/-35, p = 0.001) fiber diet but no differences were seen in fecal neutral sterol elimination. The treatment difference in fecal lithocholic acid output related to the difference in serum PSA (r = 0.57, p = 0.035). CONCLUSIONS: A small but statistically significantly lower serum PSA was seen in healthy men consuming soluble fiber, which was not related to changes in serum sex hormones but was related to the increased lithocholic acid output as a possible marker of increased fecal steroid elimination. The effect of soluble fiber on prostatic disease may warrant further investigation.

Adult↗

Testing non-linearity and directedness of interactions between neural groups in the macaque inferotemporal cortex.

Information processing in the visual cortex depends on complex and context sensitive patterns of interactions between neuronal groups in many different cortical areas. Methods used to date for disentangling this functional connectivity presuppose either linearity or instantaneous interactions, assumptions that are not necessarily valid. In this paper a general framework that encompasses both linear and non-linear modelling of neurophysiological time series data by means of Local Linear Non-linear Autoregressive models (LLNAR) is described. Within this framework a new test for non-linearity of time series and for non-linearity of directedness of neural interactions based on LLNAR is presented. These tests assess the relative goodness of fit of linear versus non-linear models via the bootstrap technique. Additionally, a generalised definition of Granger causality is presented based on LLNAR that is valid for both linear and non-linear systems. Finally, the use of LLNAR for measuring non-linearity and directional influences is illustrated using artificial data, reference data as well as local field potentials (LFPs) from macaque area TE. LFP data is well described by the linear variant of LLNAR. Models of this sort, including lagged values of the preceding 25 to 60 ms, revealed the existence of both uni- and bi-directional influences between recording sites.

Action Potentials↗

Precisely synchronized oscillatory firing patterns require electroencephalographic activation.

Neuronal response synchronization with millisecond precision has been proposed to serve feature binding in vision and should therefore, like visual experience, depend on central states. Here we test this hypothesis by examining the occurrence and strength of response synchronization in areas 17 and 18 of anesthetized cats as a function of central states. These were assessed from the frequency content of the electroencephalogram, low power in the delta and high power in the gamma frequency ranges (here 20-70 Hz) being considered as a signature of activated states. We evaluated both spontaneous state changes and transitions induced by electrical stimulation of the mesencephalic reticular formation. During states of low central activation, visual responses were robust but lacked signs of precise synchronization. At intermediate levels of activation, responses became synchronized and exhibited an oscillatory patterning in the range of 70-105 Hz. At higher levels of activation, a different pattern of response synchronization and oscillatory modulation appeared, oscillation frequency now being in the range of 20-65 Hz. The strength of response synchronization and oscillatory modulation in the 20-65 Hz range increased with further activation and was associated with a decrease in oscillation frequency. We propose that the oscillatory patterning in the 70-105 Hz range is attributable to oscillatory retinothalamic input and that a minimal level of activation is necessary for cortical neurons to follow this oscillatory pattern. In contrast, the synchronization of responses at oscillation frequencies in the 20-65 Hz range appears to result from intracortical synchronizing mechanisms, which become progressively more effective as central activation increases. Surprisingly, enhanced synchronization and oscillatory modulation in the gamma frequency range were not associated with consistent increases in response amplitude, excluding a simple relation between central activation and neuronal discharge rate. The fact that intracortical synchronizing mechanisms are particularly effective during states of central activation supports the hypothesis that precise synchronization of responses plays a role in sensory processing.

Animals↗

Patterns of synchronization in the superior colliculus of anesthetized cats.

Sensorimotor transformations in the mammalian superior colliculus (SC) are mediated by large sets of distributed neurons. For such distributed coding systems, stimulus superposition poses problems attributable to the merging of neural populations coding for different stimuli. Such superposition problems could be overcome by synchronization of neuronal discharges, because it allows the selection of a subset of distributed responses for further joint processing. To assess the putative role of such a temporal binding mechanism in the SC, we have applied correlation analysis to visually evoked collicular activity. We performed recordings of single-unit and multiunit activity in the SC of anesthetized and paralyzed cats with multiple electrodes. Autocorrelation analysis revealed that collicular neurons often discharged in broad (20-100 msec) bursts or with an oscillatory patterning in the alpha- and beta-frequency range. Significantly modulated cross-correlograms were observed in 50% (128 of 258) of the collicular multiunit recording pairs, and for these pairs significant correlations occurred in 44% of the stimulation epochs. For the single-unit pairs, significant interactions were observed in 14 of 48 cases studied (29%). Collicular cross-correlograms were often oscillatory, and these oscillations covered a broad frequency range of up to 100 Hz, with a predominance of oscillation frequencies in the alpha- and beta-range. In the majority of the significant correlograms (64%) the phase lag of the center peak was <5 msec. The probability of collicular synchronization increased with the overlap of the receptive fields and the proximity of the recording sites. Correlations were also observed between cells in the superficial and deep SC layers. Collicular synchronization required activation of the respective cells with a single coherent stimulus and broke down when the neurons were activated with two different stimuli. These data are consistent with the notion that collicular synchrony could define assemblies of functionally related cells.

Anesthesia, General↗

Matching the modules: cortical maps and long-range intrinsic connections in visual cortex during development.

Visual cortical neurons exhibit a high degree of response selectivity and are grouped into small columns according to their response preferences. The columns are located at regularly spaced intervals covering the whole cortical representation of the visual field with a modular system of feature-selective neurons. The selectivity of these cells and their modular arrangement is thought to emerge from interactions in the network of specific intracortical and thalamocortical connections. Understanding the ontogenesis of this complex structure and contributions of intrinsic and extrinsic, experience-dependent mechanisms during cortical development can provide new insights into the way the visual cortex processes information about the environment. Available data about the development of connections and response properties in the visual cortex suggest that maturation proceeds in two distinct steps. In the first phase, mechanisms inherent to the cortex establish a crude framework of interconnected neural modules which exhibit the basic but still immature traits of the adult state. Relevant mechanisms in this phase are assumed to consist of molecular cues and patterns of spontaneous neural activity in cortical and corticothalamic interconnections. In a second phase, the primordial layout becomes refined under the control of visual experience establishing a fine-tuned network of connections and mature response properties.

Animals↗

Temporal binding, binocular rivalry, and consciousness.

Cognitive functions like perception, memory, language, or consciousness are based on highly parallel and distributed information processing by the brain. One of the major unresolved questions is how information can be integrated and how coherent representational states can be established in the distributed neuronal systems subserving these functions. It has been suggested that this so-called "binding problem" may be solved in the temporal domain. The hypothesis is that synchronization of neuronal discharges can serve for the integration of distributed neurons into cell assemblies and that this process may underlie the selection of perceptually and behaviorally relevant information. As we intend to show here, this temporal binding hypothesis has implications for the search of the neural correlate of consciousness. We review experimental results, mainly obtained in the visual system, which support the notion of temporal binding. In particular, we discuss recent experiments on the neural mechanisms of binocular rivalry which suggest that appropriate synchronization among cortical neurons may be one of the necessary conditions for the buildup of perceptual states and awareness of sensory stimuli.

Arousal↗

Synchronous oscillations in the cat retina.

Retinal ganglion cells exhibit oscillatory responses which are precisely synchronized over large distances. Here we examined, with multi-electrode recordings, the time course of synchronization during spontaneous and stimulus-driven oscillatory activity. Spontaneous discharges showed synchronized oscillations at approximately 30 Hz, which were occasionally associated with slower superimposed oscillations in the range of 1-5 Hz. Stationary stimuli or moving gratings induced synchronous oscillations at higher frequencies (mean of 79.0 +/- 20.0 Hz for OFF- and 91.7 +/- 11.7 Hz for ON-responses), with time lags of a few milliseconds. At response onset, the first few oscillatory cycles were occasionally time locked to the stimulus. Thereafter, synchronization became independent of stimulus coordination and was exclusively due to neuronal interactions. Oscillatory modulation emerged rapidly and was sustained throughout the responses while oscillation frequency decreased gradually. This periodic patterning of responses persisted despite brief and local occlusion of stimuli, suggesting that synchronous oscillations emerge from population dynamics and entrain cells even if they are intermittently silenced.

Action Potentials↗

Activation of Heschl's gyrus during auditory hallucinations.

Apart from being a common feature of mental illness, auditory hallucinations provide an intriguing model for the study of internally generated sensory perceptions that are attributed to external sources. Until now, the knowledge about the cortical network that supports such hallucinations has been restricted by methodological limitations. Here, we describe an experiment with paranoid schizophrenic patients whose on- and offset of auditory hallucinations could be monitored within one functional magnetic resonance imaging (fMRI) session. We demonstrate an increase of the blood oxygen level-dependent (BOLD) signal in Heschl's gyrus during the patients' hallucinations. Our results provide direct evidence of the involvement of primary auditory areas in auditory verbal hallucinations and establish novel constraints for psychopathological models.

Acoustic Stimulation↗

Time as coding space?

There is increasing evidence that neuronal networks can operate with a temporal resolution in the millisecond range. In principle, this provides the option to encode information not only in the amplitude of neuronal responses but also in the precise temporal relations between the discharges of distributed neurons.

Acoustic Stimulation↗

Cytology of pituitary thyrotroph hyperplasia in protracted primary hypothyroidism.

Pituitary thyrotroph hyperplasia, a rare cause of pituitary enlargement, is usually associated with protracted primary hypothyroidism. We present here a case of pituitary thyrotroph hyperplasia in a 51 year old woman who was thought to have a pituitary macroadenoma with suprasellar extension. The cytologic investigation of the intraoperative touch preparation identified hyperplastic thyrotrophs, provided the correct diagnosis and helped to limit further aggressive surgical removal of the lesion, which is known to regress after adequate thyroid hormone replacement therapy. This is the first study to describe the cytologic features of pituitary thyrotroph hyperplasia confirmed subsequently by histology, immunocytochemistry and transmission electron microscopy.

Adenoma↗

Genetic and epigenetic regulation of NMDA receptor expression in the rat visual cortex.

The susceptibility of cortical networks to use-dependent modifications declines with age (critical period) and this decline of neuronal plasticity during development is paralleled by the shortening of NMDA receptor EPSCs. We showed previously in the somatosensory cortex that the shortening of NMDA receptor kinetics correlates with a developmentally-regulated increase in the NR2A subunit expression. Here we examine whether this developmental regulation of NR2A expression is related to the duration of critical periods and whether it is influenced by experience. Functional NMDA receptors and their molecular characteristics are studied in identified layer IV neurons of rat visual cortex. In this structure the time course of the critical period differs from that in the somatosensory cortex and can be changed by sensory deprivation, thus permitting examination of correlations between the time course of receptor expression and the duration of the critical period. We find that the developmental expression of the NR2A subunit is delayed compared with the somatosensory cortex, in agreement with the prolonged critical period in the visual cortex. Moreover, sensory deprivation further delays the developmental change in the NMDA receptor subunit composition, demonstrating the activity dependence of this process and strengthening the correlation between changes in subunit composition and the time course of the critical period.

Aging↗

The myth of upright vision. A psychophysical and functional imaging study of adaptation to inverting spectacles.

The adaptation to inverting prisms and mirror spectacles was studied in four subjects over periods of six to ten days. Subjects showed rapid adaptation of visuomotor functions, but did not report return of upright vision. The persistence of the transformed visual image was confirmed by the subjects' perception of shape from shading. No alteration of the retinotopy of early visual cortical areas was seen in the functional magnetic resonance images. These results are discussed in the context of previous claims of upright vision with inverting prisms and mirror spectacles.

Adaptation, Psychological↗