Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 55 records · Page 3Linked to original sources

PubMed1999

In vivo cytokine and neuroendocrine responses to endotoxin in human immunodeficiency virus-infected subjects.

The cytokine and neuroendocrine host responses to experimental challenge with lipopolysaccharide (LPS) were studied in human immunodeficiency virus (HIV)-infected subjects and uninfected control subjects. Elevations in circulating concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were significantly greater in HIV-infected subjects than control subjects after LPS challenge. All subjects showed a significant increase in circulating concentrations of adrenocorticotropin, cortisol, and norepinephrine after LPS challenge, but there was not a significant difference between the responses of these hormones in the HIV-infected and -uninfected subjects. Compared with the control subjects, the HIV-infected subjects had a significantly reduced IL-10 response and a reduced IL-1 receptor antagonist response. It is concluded that the TNF-alpha, IL-6, IL-8, and IL-10 cytokine responses to LPS in vivo are disrupted in HIV subjects but that this is not related to disruption of the hypothalamo-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗

PubMed1999

Cold face test demonstrates parasympathetic cardiac dysfunction in familial dysautonomia.

In familial dysautonomia (FD), i.e., Riley-Day syndrome, parasympathetic dysfunction has not been sufficiently evaluated. The cold face test is a noninvasive method of activating trigeminal brain stem cardiovagal and sympathetic pathways and can be performed in patients with limited cooperation. We performed cold face tests in 11 FD patients and 15 controls. For 60 s, cold compresses (0-1 degrees C) were applied to the cheeks and forehead while we monitored heart rate, respiration, beat-to-beat radial artery blood pressure, and laser-Doppler skin blood flow at the first toe pulp. From these measurements heart rate variability parameters were calculated: root mean square of successive differences (RMSSD), coefficient of variation (CV), low- and high-frequency (LF and HF, respectively) power spectra of the electrocardiogram, and the LF transfer function gain between blood pressure and heart rate. All patients perceived cold stimulation and acknowledged discomfort. In controls, heart rate and skin blood flow decreased significantly during cold face test; in patients, both parameters decreased only briefly and not significantly. In controls, blood pressure, RMSSD, CV, and heart rate HF-power spectra increased but remained unchanged in patients. Respiration, as well as heart rate LF power spectra, did not change in either group. In controls, LF transfer function gain between blood pressure and heart rate indicated that bradycardia was not secondary to blood pressure increase. We conclude that the cold face test demonstrated that patients with FD have a reduced cardiac parasympathetic response, which implies efferent parasympathetic dysfunction.

Adolescent↗

PubMed1999

The role of neurotrophins in developmental cortical plasticity.

PURPOSE: It has been proposed that experience dependent maturation and reorganization in the neocortex might be based on the activity dependent competition between different sets of axons for growth related molecules such as neurotrophins. In the present study we tested this hypothesis by examination of the effects of external administration of NGF and BDNF on the experience dependent rearrangement of thalamocortical connections after monocular deprivation (MD) in the developing cat visual cortex. METHODS: The visual cortices of kittens were infused intracortically either with BDNF, NGF or cytochrome C while the animals were subjected to MD for one week during the peak of the critical period (postnatal day 26 to postnatal day 40). Subsequently cortical neuronal responses were assessed with optical (optical imaging of intrinsic signals) and single unit recording techniques. RESULTS: In control hemispheres treated with cytochrome C, MD had caused the expected shift of OD towards the normal eye. Also hemispheres treated with NGF exhibited a strong shift of OD towards the open eye. However, in the BDNF infused hemispheres OD had shifted towards the deprived eye in a zone extending 2.5-3.5 mm from the infusion cannula and neurons had lost their orientation selectivity. In an adjacent transition zone both eyes activated the cortex equally well and responses were again tuned for orientation and at still larger distances OD was shifted towards the normal eye. CONCLUSIONS: The present data support the concept of an involvement of neurotrophins in cortical plasticity. However, our observations suggest for both neurotrophins, NGF and BDNF, a more complex role in the developing neocortex than serving simply as the substrate of an activity dependent competition process within the visual cortex. Moreover, the outcome of our study indicaties strong differences between BDNF and NGF concerning their involvement and locus of action in developmental plasticity.

Journal Article↗

PubMed1998

Consciousness and the structure of neuronal representations.

The hypothesis is defended that brains expressing phenomenal awareness are capable of generating metarepresentations of their cognitive processes, these metarepresentations resulting from an iteration of self-similar cortical operations. Search for the neuronal substrate of awareness therefore converges with the search for the nature of neuronal representations. It is proposed that evolved brains use two complementary representational strategies. One consists of the generation of neurons responding selectively to a particular constellation of features and is based on selective recombination of inputs in hierarchically structured feedforward architectures. The other relies on the dynamic association of feature-specific cells into functionally coherent cell assemblies that, as a whole, represent the constellation of features defining a particular perceptual object. Arguments are presented that favour the notion that the metarepresentations supporting awareness are established in accordance with the second strategy. Experimental data are reviewed that are compatible with the hypothesis that evolved brains use assembly codes for the representation of contents and that these assemblies become organized through transient synchronization of the discharges of associated neurons. It is argued that central states favouring the formation of assembly-based representations are similar to those favouring awareness.

Animals↗

PubMed1998

Synchronization of visual responses between the cortex, lateral geniculate nucleus, and retina in the anesthetized cat.

Synchronization of spatially distributed responses in the cortex is often associated with periodic activity. Recently, synchronous oscillatory patterning was described for visual responses in retinal ganglion cells that is reliably transmitted by the lateral geniculate nucleus (LGN), raising the question of whether oscillatory inputs contribute to synchronous oscillatory responses in the cortex. We have made simultaneous multi-unit recordings from visual areas 17 and 18 as well as the LGN and the retina to examine the interactions between subcortical and cortical synchronization mechanisms. Strong correlations of oscillatory responses were observed between retina, LGN, and cortex, indicating that cortical neurons can become synchronized by oscillatory activity relayed through the LGN. This feedforward synchronization occurred with oscillation frequencies in the range of 60-120 Hz and was most pronounced for responses to stationary flashed stimuli and more frequent for cells in area 18 than in area 17. In response to moving stimuli, by contrast, subcortical and cortical oscillations dissociated, proving the existence of independent subcortical and cortical mechanisms. Subcortical oscillations maintained their high frequencies but became transient. Cortical oscillations were now dominated by a cortical synchronizing mechanism operating in the 30-60 Hz frequency range. When the cortical mechanism dominated, LGN responses could become phase-locked to the cortical oscillations via corticothalamic feedback. In summary, synchronization of cortical responses can result from two independent but interacting mechanisms. First, a transient feedforward synchronization to high-frequency retinal oscillations, and second, an intracortical mechanism, which operates in a lower frequency range and induces more sustained synchronization.

Animals↗

PubMed1998

Functional imaging of mirror and inverse reading reveals separate coactivated networks for oculomotion and spatial transformations.

Echoplanar functional magnetic resonance imaging (fMRI) was used to localize the cortical areas involved in the analysis of spatially transformed letter strings. Significant increases of the blood oxygen level-dependent (BOLD) signal for transformed vs normal reading were observed in the superior parietal lobule (SPL), along the intraparietal sulcus (IPS), in the frontal eye fields (FEF), and in the latero-occipital area LO. The respective contributions of oculomotor and spatial transformation areas to this activation pattern were separated by means of a control condition involving the execution and suppression of eye movements. Areas activated in association with the control of eye movements included the superior parietal lobule and the frontal eye fields. The cooperation of different brain areas was analysed by correlating the time course of task-dependent BOLD signal changes in these areas. This correlation analysis revealed coactivation of occipitotemporal object recognition areas and a spatial transformation area in the intraparietal sulcus during the reading of transformed letter strings. We suggest that cortical systems that are coactivated during complex cognitive tasks can be differentiated by the correlation analysis of BOLD signal time courses in spatially separate brain areas.

Adult↗

PubMed1998

Elevated high-density lipoprotein cholesterol and dietary fat intake in women with cyclic mastopathy.

OBJECTIVE: This study was designed to examine the contribution of plasma lipids to the pathophysiology of cyclic mastopathy, before and after consideration of diet and sex hormones. STUDY DESIGN: Thirty-four women with severe cyclic mastopathy (case patients) and 29 women without cyclic mastopathy (control subjects) recorded their breast symptoms daily during 1 menstrual cycle. During each menstrual phase (follicular, early luteal, late luteal, and menstrual) they prospectively completed 2 24-hour dietary diaries, provided blood for lipid and hormone assays, and underwent anthropometric measurements. RESULTS: Mean age was 34 years. Premenstrual breast swelling and tenderness were significantly more severe in case patients (P < .0001). Cyclic change (late luteal vs follicular) of high-density lipoprotein cholesterol differed between case patients and control subjects, with case patients having a relative excess of high-density lipoprotein cholesterol in the premenstrual phase (P = .01). Dietary fat intake was greater throughout the cycle in case patients (37.5 vs 33.7% of calories, P = .02), and case patients reported increased appetite in the premenstrual phase (P = .01). In multivariate analyses the contributions of mean dietary fat intake and of cyclic change in high-density lipoprotein cholesterol were independently significant, with odds ratios for upper versus lower quintiles being slightly >5. CONCLUSIONS: Women with cyclic mastopathy had a relative excess of high-density lipoprotein cholesterol during the symptomatic late luteal phase of the menstrual cycle and a higher fat intake throughout the cycle than did control subjects. These observations support the hypothesis that lipids (notably high-density lipoprotein cholesterol) and a high-fat diet play a role in the pathophysiologic characteristics of cyclic mastopathy.

Adult↗

PubMed1998

Hyperglycemia during normothermic cardiopulmonary bypass: the role of the kidney.

BACKGROUND: Hyperglycemia commonly occurs during cardiopulmonary bypass. We studied the quantitative impact of glucose input and its renal excretion on hyperglycemia during cardiopulmonary bypass. METHODS: The quantity of glucose infused and metabolite and hormone concentrations in plasma, as well as oxygen consumption, carbon dioxide production, and renal glucose excretion, were determined before, during, and after cardiopulmonary bypass in 8 patients. RESULTS: Hyperglycemia (14 to 29 mmol/L) was accompanied by an increase in plasma insulin levels. The degree of hyperglycemia was directly related to the amount of glucose infused. The rate of oxygen consumption did not decrease and the rate of urea appearance (gluconeogenesis) did not rise. Despite a very high filtered load of glucose, there was very little glucosuria, indicating a markedly enhanced renal absorption of glucose. CONCLUSIONS: Hormonal and metabolic factors permit the development of hyperglycemia during cardiopulmonary bypass but its severity depends on the quantity of glucose infused and, what appears to be a new finding, a markedly enhanced renal reabsorption of filtered glucose. Thus the kidney plays an important role in the development of severe hyperglycemia during cardiopulmonary bypass.

Absorption↗

PubMed1998

Two segmentation mechanisms with differential sensitivity for colour and luminance contrast.

In a texture-segregation paradigm, subjects were asked to detect figures whose elements were segregated from background either because of temporal offset or because of differing orientations. Texture elements were either isoluminant or had high or low luminance contrast. At high luminance contrast, figures could be segregated both on the basis of orientation and temporal cues whereby temporal offsets as short as 10 msec supported detection. At isoluminance, orientation defined figures were as readily distinguishable as in the high contrast condition but temporally defined figures were perceived only for offset intervals > 50 msec. With low luminance contrast, performance for orientation defined figures was impaired relative to the high contrast condition, but for temporally defined figures, it was superior to the isoluminant condition; detection was possible for offset intervals as short as 22 msec. These results suggest that the temporal and orientation cues which support scene segmentation are transmitted by both the luminance and colour sensitive pathways. However, if temporal offsets are < 50 msec, segmentation of temporally defined figures is supported only by the luminance sensitive system.

Adult↗

PubMed1998

Modification of discharge patterns of neocortical neurons by induced oscillations of the membrane potential.

We investigated, with whole-cell recordings from rat visual cortex slices, how sinusoidal modulation of the membrane potential affects signal transmission. Subthreshold oscillations activate tetrodotoxin sensitive, transient inward currents whose threshold, phase lag and duration change with modulation frequency. These periodically recurring phases of enhanced excitability affect synaptic transmission in two ways. Weak and short lasting excitatory postsynaptic potentials evoke discharges only if they are coincident within a few milliseconds with these active membrane responses. Long-lasting, N-methyl-D-aspartate-mediated or polysynaptic excitatory postsynaptic potentials, by contrast, evoke trains of spikes, that are precisely time-locked to the oscillations and may last for more than 100 ms. Thus, oscillations impose a precise temporal window for the integration of synaptic inputs, favouring coincidence detection and they generate temporally-structured responses whose timing and amplitude are largely independent of the input. These properties are ideally suited for the synchronization of neuronal activity and the encoding of information in the precise timing of discharges. A preliminary account of these data has appeared in an abstract form [Volgushev M. et al. (1995) Eur. J Neurosci. 8, 77].

Action Potentials↗

PubMed1998

Differential patterns of semaphorin expression in the developing rat brain.

Semaphorins are a large family of cell-surface and secreted proteins that have been shown to function as chemorepellents or inhibitors of growth cones of peripheral neurons, yet little is known about their role in patterning central pathways. In order to examine whether semaphorins may be involved in guiding the formation of the reciprocal thalamocortical connections in the rat, we have analysed the spatial and temporal expression of five recently identified rodent semaphorins (semB, C, D, F and G) using in situ hybridization. Transcripts of all five genes were present throughout the period examined (E15-P7) and displayed highly specific spatiotemporal distributions. We have based our discussion of putative semaphorin effects on their known functions as chemorepellents and found their spatiotemporal expression patterns compatible with such a role in several developmental events. Specifically, semaphorins are in the position to: (i) prevent neurite extension into the ventricular neuroepithelium throughout the brain; (ii) confer non-permissive properties to the embryonic cortical plate, hence regulating the radial invasion of corticopetal afferents; (iii) confine axonal extension to the intermediate zone and subplate; (iv) maintain the fasciculated state of thalamocortical and corticothalamic axons, and prevent them from branching while they grow through the striatum; and (v) restrict the terminal arborizations of thalamic afferents to layer IV. The evidence that different semaphorin genes are often co-expressed further suggests that the various molecules might interact in synergistic ways. Taken together, our results support the hypothesis that semaphorins could act as guidance signals in the development of the thalamocortical projections and suggest that innervation specificity is achieved through the combined action of multiple guidance cues. Furthermore, these data provide a basis for the design of functional assays and the study of mice carrying knockouts in specific semaphorin genes.

Animals↗

PubMed1998

The constructive nature of vision: direct evidence from functional magnetic resonance imaging studies of apparent motion and motion imagery.

Echoplanar functional magnetic resonance imaging was used to monitor activation changes of brain areas while subjects viewed apparent motion stimuli and while they were engaged in motion imagery. Human cortical areas MT (V5) and MST were the first areas of the 'dorsal' processing stream which responded with a clear increase in signal intensity to apparent motion stimuli as compared with flickering control conditions. Apparent motion of figures defined by illusory contours evoked greater activation in V2 and MT/MST than appropriate control conditions. Several areas of the dorsal pathway (V3A, MT/MST, areas in the inferior and superior parietal lobule) as well as prefrontal areas including FEF and BA 9/46 responded strongly when subjects merely imagined moving stimuli which they had seen several seconds before. The activation during motion imagery increased with the synaptic distance of an area from V1 along the dorsal processing stream. Area MT/MST was selectively activated during motion imagery but not during a static imagery control condition. The comparison between the results obtained with objective motion, apparent motion and imagined motion provides further insights into a complex cortical network of motion-sensitive areas driven by bottom-up and top-down neural processes.

Adult↗

PubMed1998

The response of cat visual cortex to flicker stimuli of variable frequency.

We examined the possibility that neurons or groups of neurons along the retino-cortical transmission chain have properties of tuned oscillators: To this end, we studied the resonance properties of the retino-thalamo-cortical system of anaesthetized cats by entraining responses with flicker stimuli of variable frequency (2-50 Hz). Responses were assessed from multi-unit activity (MUA) and local field potentials (LFPs) with up to four spatially segregated electrodes placed in areas 17 and 18. MUA and LFP responses were closely related, units discharging with high preference during LFP negativity. About 300 ms after flicker onset, responses stabilized and exhibited a highly regular oscillatory patterning that was surprisingly similar at different recording sites due to precise stimulus locking. Fourier transforms of these steady state oscillations showed maximal power at the inducing frequency and consistently revealed additional peaks at harmonic frequencies. The frequency-dependent amplitude changes of the fundamental and harmonic response components suggest that the retino-cortical system is entrainable into steady state oscillations over a broad frequency range and exhibits preferences for distinct frequencies in the theta- or slow alpha-range, and in the beta- and gamma-band. Concomitant activation of the mesencephalic reticular formation increased the ability of cortical cells to follow high frequency stimulation, and enhanced dramatically the amplitude of first- and second-order harmonics in the gamma-frequency range between 30 and 50 Hz. Cross-correlations computed between responses recorded simultaneously from different sites revealed pronounced synchronicity due to precise stimulus locking. These results suggest that the retino-cortical system contains broadly tuned, strongly damped oscillators which altogether exhibit at least three ranges of preferred frequencies, the relative expression of the preferences depending on the central state. These properties agree with the characteristics of oscillatory responses evoked by non-temporally modulated stimuli, and they indicate that neuronal responses along the retino-cortical transmission chain can become synchronized with precision in the millisecond range not only by intrinsic interactions, but also by temporally structured stimuli.

Animals↗

PubMed1998

The layout of orientation and ocular dominance domains in area 17 of strabismic cats.

In the primary visual cortex of strabismic cats, the elimination of correlated activity between the two eyes enhances the segregation of the geniculocortical afferents into alternating ocular dominance domains. In addition, both tangential intracortical fibres and neuronal synchronization are severely reduced between neurons activated by different eyes. Consequently, ocular dominance columns belonging to different eyes are functionally rather independent. We wondered whether this would also affect the organization of orientation preference maps. To this end, we visualized the functional architecture of area 17 of strabismic cats with both optical imaging based on intrinsic signals and double labelling of orientation and ocular dominance columns with [14C]2-deoxyglucose and [3H]proline. As expected, monocular iso-orientation domains had a patchy appearance and differed for the two eyes, leading to a clear segregation of the ocular dominance domains. Comparison of 'angle maps' revealed that orientation domains exhibit a pinwheel organization as in normally reared cats. Interestingly, the map of orientation preferences did not show any breaks at the borders between ocular dominance columns: iso-orientation domains were continuous across these borders. In addition, iso-orientation contours tended to cross the borders of adjacent ocular dominance columns at right angles. These data suggest that the basic relations between the layout of orientation maps and ocular dominance columns are not disturbed by artificial decorrelation of binocular input. Therefore in cat area 17, the orientation map does not seem to be modified by experience-dependent changes of thalamic input connections. This suggests the possibility that use-dependent rearrangement of geniculocortical afferents into ocular dominance columns is due to Hebbian modifications whereby postsynaptic responsivity is constrained by the scaffold of the orientation map.

Animals↗

PubMed1998

Integrative aspects of a human model of endotoxemia.

The production of tumor necrosis factor (TNF)-alpha is a key step in the response to sepsis and has powerful local and systemic effects on the host. These systemic responses include a complex cascade of centrally mediated endocrine and neural responses. An integrative model of these regulatory cytokine-neuroendocrine interactions in humans is presented. The rapid kinetics of these responses are illustrated by data showing the response of normal human subjects to experimental endotoxemia. Appreciation of the integrative biology of the in vivo response to experimental endotoxemia can provide a framework for the design of experiments aimed at examining the effects of physical training paradigms on particular cytokine and neuroendocrine pathways.

Adrenocorticotropic Hormone↗

PubMed1998

Correlation analysis of corticotectal interactions in the cat visual system.

We have studied the temporal relationship between visual responses in various visual cortical areas [17, 18, postero medial lateral suprasylvian (PMLS), postero lateral lateral suprasylvian (PLLS), 21a]) and the superficial layers of the cat superior colliculus (SC). To this end, simultaneous recordings were performed in one or several visual cortical areas and the SC of anesthetized paralyzed cats, and visually evoked multiunit responses were subjected to correlation analysis. Significant correlations occurred in 117 (24%) of 489 cortex-SC pairs and were found for all cortical areas recorded. About half of the significant correlograms showed an oscillatory modulation. In these cases, oscillation frequencies covered a broad range, the majority being in the alpha- and beta-band. On average, significant center peaks in cross-correlograms had a modulation amplitude of 0.34. Our analysis revealed a considerable intertrial variability of correlation patterns with respect to both correlation strength and oscillation frequency. Furthermore, cortical areas differed in their corticotectal correlation patterns. The percentage of cells involved a corticotectal correlation, as well as the percentage of significantly modulated correlograms in such cases, was low for areas 17 and PMLS but high for areas 18 and PLLS. Analysis of the cortical layers involved in these interactions showed that consistent temporal relationships between cortical and collicular responses were not restricted to layer V. Our data demonstrate a close relationship between corticotectal interactions and intracortical or intracollicular synchronization. Trial-by-trial analysis from these sites revealed a clear covariance of corticotectal correlations with intracortical synchronization. The probability of observing corticotectal interactions increased with enhanced local cortical and collicular synchronization and, in particular, with interareal cortical correlations. Corticotectal correlation patterns resemble in many ways those described among areas of the visual cortex. However, the correlations observed are weaker than those between nearby cortical sites, exhibit usually broader peaks and for some cortical areas show consistent phase-shifts. Corticotectal correlations represent population phenomena that reflect both the local and global temporal organization of activity in the cortical and collicular network and do not arise from purely monosynaptic interactions. Our findings show that both striate and extrastriate inputs affect the superficial SC in a cooperative manner and, thus, do not support the view that responses in the superficial SC depend exclusively on input from the primary visual areas as implied by the concept of "two corticotectal systems." We conclude that the corticotectal projections convey temporal activation patterns with high reliability, thus allowing the SC evaluation of information encoded in the temporal relations between responses of spatially disseminated cortical neurons. As a consequence, information distributed across multiple cortical areas can affect the SC neurons in a coherent way.

Animals↗

PubMed1998

Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study. Case report.

The authors report on the morphological features of a pituitary adenoma that produced growth hormone (GH) and adrenocorticotropic hormone (ACTH). This hormone combination produced by a single adenoma is extremely rare; a review of the available literature showed that only one previous case has been published. The tumor, which was removed from a 62-year-old man with acromegaly, was studied by histological and immunocytochemical analyses, transmission electron microscopy, immunoelectron microscopy, and in situ hybridization. When the authors used light microscopy, the tumor appeared to be a bimorphous mixed pituitary adenoma composed of two separate cell types: one cell population synthesized GH and the other ACTH. The cytogenesis of pituitary adenomas that produce more than one hormone is obscure. It may be that two separate cells--one somatotroph and one corticotroph--transformed into neoplastic cells, or that the adenoma arose in a common stem cell that differentiated into two separate cell types. In this case immunoelectron microscopy conclusively demonstrated ACTH in the secretory granules of several somatotrophs. This was associated with a change in the morphological characteristics of secretory granules. Thus it is possible that the tumor was originally a somatotropic adenoma that began to produce ACTH as a result of mutations that occurred during tumor progression.

Acromegaly↗

PubMed1997

Synchronization of oscillatory responses in visual cortex correlates with perception in interocular rivalry.

In subjects suffering from early onset strabismus, signals conveyed by the two eyes are not perceived simultaneously but in alternation. We exploited this phenomenon of interocular suppression to investigate the neuronal correlate of binocular rivalry in primary visual cortex of awake strabismic cats. Monocularly presented stimuli that were readily perceived by the animal evoked synchronized discharges with an oscillatory patterning in the gamma-frequency range. Upon dichoptic stimulation, neurons responding to the stimulus that continued to be perceived increased the synchronicity and the regularity of their oscillatory patterning while the reverse was true for neurons responding to the stimulus that was no longer perceived. These differential changes were not associated with modifications of discharge rate, suggesting that at early stages of visual processing the degree of synchronicity rather than the amplitude of responses determines which signals are perceived and control behavioral responses.

Animals↗