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Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 19 recordsLinked to original sources
PubMed2006

Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet.

BACKGROUND: A dietary portfolio of cholesterol-lowering ingredients has proved effective in reducing serum cholesterol. However, it is not known whether this dietary combination will also affect hematologic risk factors for coronary heart disease (CHD). Reductions in hematocrit and polymorphonuclear leukocytes have been reported to improve cardiovascular risk. We, therefore, report changes in hematological indices, which have been linked to cardiovascular health, in a 1-year assessment of subjects taking an effective dietary combination (portfolio) of cholesterol-lowering foods. METHODS: For 12 months, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (23 g/1000 kcal). Fifty-five subjects completed the study. RESULTS: Over the 1 year, data on completers indicated small but significant reductions in hemoglobin (-1.5+/-0.6 g/l, P=0.013), hematocrit (-0.007+/-0.002 l/l, P<0.001), red cell number (-0.07+/-0.02 10(9)/l, P<0.001) and neutrophils (-0.34+/-0.13 10(9)/l, P=0.014). Mean platelet volume was also increased (0.16+/-0.07 fl, P=0.033). The increase in red cell osmotic fragility (0.05+/-0.03 g/l, P=0.107) did not reach significance. CONCLUSIONS: These small changes in hematological indices after a cholesterol-lowering diet are in the direction, which would be predicted to reduce CHD risk. Further research is needed to clarify whether the changes observed will contribute directly or indirectly to cardiovascular benefits beyond those expected from reductions previously seen in serum lipids and blood pressure.

Adult↗
PubMed2006

Retinotopic effects during spatial audio-visual integration.

The successful integration of visual and auditory stimuli requires information about whether visual and auditory signals originate from corresponding places in the external world. Here we report crossmodal effects of spatially congruent and incongruent audio-visual (AV) stimulation. Visual and auditory stimuli were presented from one of four horizontal locations in external space. Seven healthy human subjects had to assess the spatial fit of a visual stimulus (i.e. a gray-scaled picture of a cartoon dog) and a simultaneously presented auditory stimulus (i.e. a barking sound). Functional magnetic resonance imaging (fMRI) revealed two distinct networks of cortical regions that processed preferentially either spatially congruent or spatially incongruent AV stimuli. Whereas earlier visual areas responded preferentially to incongruent AV stimulation, higher visual areas of the temporal and parietal cortex (left inferior temporal gyrus [ITG], right posterior superior temporal gyrus/sulcus [pSTG/STS], left intra-parietal sulcus [IPS]) and frontal regions (left pre-central gyrus [PreCG], left dorsolateral pre-frontal cortex [DLPFC]) responded preferentially to congruent AV stimulation. A position-resolved analysis revealed three robust cortical representations for each of the four visual stimulus locations in retinotopic visual regions corresponding to the representation of the horizontal meridian in area V1 and at the dorsal and ventral borders between areas V2 and V3. While these regions of interest (ROIs) did not show any significant effect of spatial congruency, we found subregions within ROIs in the right hemisphere that showed an incongruency effect (i.e. an increased fMRI signal during spatially incongruent compared to congruent AV stimulation). We interpret this finding as a correlate of spatially distributed recurrent feedback during mismatch processing: whenever a spatial mismatch is detected in multisensory regions (such as the IPS), processing resources are re-directed to low-level visual areas.

Acoustic Stimulation↗
PubMed2005

Direct comparison of dietary portfolio vs statin on C-reactive protein.

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) markedly reduce serum cholesterol and have anti-inflammatory effects. The effect of cholesterol-lowering diets on inflammatory biomarkers is less well known. OBJECTIVE: To compare the efficacy of a dietary combination (portfolio) of cholesterol-lowering foods vs a statin in reducing C-reactive protein (CRP) as a biomarker of inflammation linked to increased cardiovascular disease risk. METHODS: In all, 34 hyperlipidemic subjects completed three 1-month treatments as outpatients in random order: a very low-saturated fat diet (control); the same diet with 20 mg lovastatin (statin); and a diet high in plant sterols (1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (portfolio). Fasting blood samples were obtained at weeks 0, 2, and 4. RESULTS: Using the complete data, no treatment reduced serum CRP. However, when subjects with CRP levels above the 75th percentile for previously reported studies (> 3.5 mg/l) were excluded, CRP was reduced similarly on both statin, -16.3 +/- 6.7% (n = 23, P = 0.013) and dietary portfolio, -23.8 +/- 6.9% (n = 25, P = 0.001) but not the control, 15.3 +/- 13.6% (n = 28, P = 0.907). The percentage CRP change from baseline on the portfolio treatment (n = 25) was greater than the control (n = 28, P = 0.004) but similar to statin treatment (n = 23, P = 0.349). Both statin and portfolio treatments were similar in reducing CRP and numerically more effective than control but only the change in portfolio was significant after the Bonferroni adjustment. CONCLUSIONS: A combination of cholesterol-lowering foods reduced C-reactive protein to a similar extent as the starting dose of a first-generation statin.

Adult↗
PubMed2004

Prospective evaluation of somatic and autonomic small fibers in selected autonomic neuropathies.

BACKGROUND: There are a number of distal and generalized small-fiber neuropathies. The neuropathologic basis is poorly understood as somatic and autonomic C fibers are not usually studied in the same region of the body. OBJECTIVE: To evaluate prospective somatic and autonomic C-fiber function in 11 healthy control subjects and 38 patients with different clinical patterns of neuropathy. METHODS: Distal small-fiber neuropathy (DSFN), peripheral neuropathy (PN), diabetic neuropathy (DN), neuropathic postural tachycardia syndrome (POTS), and idiopathic autonomic neuropathy (IAN) were evaluated. Intraepidermal nerve fiber density was used to evaluate distal somatic C fibers. Both quantitative sudomotor axon reflex test and skin norepinephrine content were measured for the biopsy site to assess distal autonomic C-fiber function. Postganglionic sudomotor, adrenergic, and cardiovagal functions were evaluated by autonomic reflex testing and quantified using a Composite Autonomic Severity Scale. RESULTS: Skin norepinephrine concentration was significantly related to CASS. DN was associated with somatic and autonomic C-fiber impairment with good agreement. POTS was associated with selective distal autonomic deficit. DSFN had combined distal somatic and C-fiber impairment. IAN showed combined and selective distal and generalized autonomic C-fiber impairment. The somatic neuropathies had C-fiber impairment affecting both populations to varying degrees. CONCLUSION: Although a general agreement exists between the loss of somatic C fibers and autonomic deficits, selective involvement occurs for specific autonomic neuropathies.

Adult↗
PubMed2003

Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension.

BACKGROUND: Pharmacological treatment of orthostatic hypotension is often limited because of troublesome supine hypertension. OBJECTIVE: To investigate a novel approach to treatment using acetylcholinesterase inhibition, based on the theory that enhanced sympathetic ganglion transmission increases systemic resistance in proportion to orthostatic needs. DESIGN: Prospective open label single dose trial. MATERIAL: 15 patients with neurogenic orthostatic hypotension caused by: multiple system atrophy (n = 7), Parkinson's disease (n = 3), diabetic neuropathy (n = 1), amyloid neuropathy (n = 1), and idiopathic autonomic neuropathy (n = 3). METHODS: Heart rate, blood pressure, peripheral resistance index (PRI), cardiac index, stroke index, and end diastolic index were monitored continuously during supine rest and head up tilt before and one hour after an oral dose of 60 mg pyridostigmine. RESULTS: There was only a modest non-significant increase in supine blood pressure and PRI. In contrast, acetylcholinesterase inhibition significantly increased orthostatic blood pressure and PRI and reduced the fall in blood pressure during head up tilt. Orthostatic heart rate was reduced after the treatment. The improvement in orthostatic blood pressure was associated with a significant improvement in orthostatic symptoms. CONCLUSIONS: Acetylcholinesterase inhibition appears effective in the treatment of neurogenic orthostatic hypotension. Orthostatic symptoms and orthostatic blood pressure are improved, with only modest effects in the supine position. This novel approach may form an alternative or supplemental tool in the treatment of orthostatic hypotension, specially for patients with a high supine blood pressure.

Acetylcholinesterase↗
PubMed2001

Synchronization of visual responses in the superior colliculus of awake cats.

Multi-unit responses to moving stimuli were recorded simultaneously from several sites in the superior colliculus of awake cats. Correlation analysis revealed that response synchronization was a prominent feature of visually evoked neural activity in both superficial and deep collicular layers. Responses at about half of the recordings separated by < or = 1 mm showed significant correlations. The synchronized responses oscillated in the gamma frequency range (30-70 Hz) which contrasts to conditions in anaesthetized cats where oscillations predominantly occurred in the alpha and beta frequency range (10-20 Hz). Response synchronization was most pronounced with coherent motion stimuli and broke down with incoherent stimuli. These results agree with previous findings on corticotectal synchronization and support the hypothesis that synchronization in the millisecond range serves to group collicular neurons into functionally coherent assemblies.

Animals↗
PubMed2001

Temporal binding and the neural correlates of sensory awareness.

Theories of binding have recently come into the focus of the consciousness debate. In this review, we discuss the potential relevance of temporal binding mechanisms for sensory awareness. Specifically, we suggest that neural synchrony with a precision in the millisecond range may be crucial for conscious processing, and may be involved in arousal, perceptual integration, attentional selection and working memory. Recent evidence from both animal and human studies demonstrates that specific changes in neuronal synchrony occur during all of these processes and that they are distinguished by the emergence of fast oscillations with frequencies in the gamma-range.

Journal Article↗
PubMed2001

Conditions of perceptual selection and suppression during interocular rivalry in strabismic and normal cats.

Presenting the two eyes with incongruent stimuli leads to the phenomenon of interocular rivalry. At any given time, one of the stimuli is perceptually suppressed in order to avoid double vision. In squinting subjects, rivalry occurs permanently also for congruent stimuli because of developmental rearrangement of cortical circuitry. In this study, we have investigated the dynamics and stimulus dependence of rivalry in six esotropic, four exotropic and three non-strabismic cats. As an indicator for perception, we used optokinetic nystagmus that was induced by moving gratings. The esotropic cats were tested for their visual acuity by means of a jumping stand procedure. The results show that one eye can dominate perception even if both eyes have equal visual acuity and are presented with stimuli of equal contrast. Strong eye dominance asymmetry was found in all but one of the tested cats. Notably, all three of the normal cats showed a clear asymmetry in perceptual selection. Measurements with varying contrast and velocity of the stimuli revealed that the influence of these parameters on perceptual selection was independent of the presence of strabismus. In all cats, the time during which a given eye dominated perception increased with the contrast and decreases with the velocity of the stimulus presented to this eye.

Animals↗
PubMed2001

Sustained extrastriate cortical activation without visual awareness revealed by fMRI studies of hemianopic patients.

Patients with lesions in the primary visual cortex (V1) may show processing of visual stimuli presented in their field of cortical blindness even when they report being unaware of the stimuli. To elucidate the neuroanatomical basis of their residual visual functions, we used functional magnetic resonance imaging in two hemianopic patients, FS and GY. In the first experiment, a rotating spiral stimulus was used to assess the responsiveness of dorsal stream areas. Although no response was detectable within denervated or destroyed early visual cortex, motion-sensitive areas (hMT+/V5) ipsilateral to the lesion showed a strong sustained hemodynamic response. In GY, this activation was at least as strong as that of his contralesional hMT+/V5 to the stimulus in the normal hemifield. In the second experiment, coloured images of natural objects were used to assess the responsiveness of ventral stream areas. Again, no activity was detectable in ipsilesional early visual areas, but extrastriate areas in the lateral occipital cortex (hMT+/V5 and LO) and within the posterior fusiform gyrus (V4/V8) showed a robust sustained hemodynamic response. In both experiments, we observed that ipsilesional areas responded to stimuli presented in either hemifield, whereas the normal hemisphere responded preferentially to stimuli in the sighted hemifield. As only one subject occasionally noticed the onset of stimulation in the impaired field, the unexpectedly strong sustained activity in ipsilesional dorsal and ventral cortical areas appears to be insufficient to generate conscious vision.

Adult↗
PubMed2001

Dynamic predictions: oscillations and synchrony in top-down processing.

Classical theories of sensory processing view the brain as a passive, stimulus-driven device. By contrast, more recent approaches emphasize the constructive nature of perception, viewing it as an active and highly selective process. Indeed, there is ample evidence that the processing of stimuli is controlled by top-down influences that strongly shape the intrinsic dynamics of thalamocortical networks and constantly create predictions about forthcoming sensory events. We discuss recent experiments indicating that such predictions might be embodied in the temporal structure of both stimulus-evoked and ongoing activity, and that synchronous oscillations are particularly important in this process. Coherence among subthreshold membrane potential fluctuations could be exploited to express selective functional relationships during states of expectancy or attention, and these dynamic patterns could allow the grouping and selection of distributed neuronal responses for further processing.

Animals↗
PubMed2001

Rapid feature selective neuronal synchronization through correlated latency shifting.

Spontaneous brain activity could affect processing if it were structured. We show that neuron pairs in cat primary visual cortex exhibited correlated fluctuations in response latency, particularly when they had overlapping receptive fields or similar orientation preferences. Correlations occurred within and across hemispheres, but only when local field potentials (LFPs) oscillated in the gamma-frequency range (40-70 Hz). In this range, LFP fluctuations preceding response onset predicted response latencies; negative (positive) LFPs were associated with early (late) responses. Oscillations below 10 Hz caused covariations in response amplitude, but exhibited no columnar selectivity or coordinating effect on latencies. Thus, during high gamma activity, spontaneous activity exhibits distinct, column-specific correlation patterns. Consequently, cortical cells undergo coherent fluctuations in excitability that enhance temporal coherence of responses to contours that are spatially contiguous or have similar orientation. Because synchronized responses are more likely than dispersed responses to undergo rapid and joint processing, spontaneous activity may be important in early visual processes.

Action Potentials↗
PubMed2001

Consciousness and the binding problem.

It is proposed that phenomenal awareness, the ability to be aware of one's sensations and feelings, emerges from the capacity of evolved brains to analyze their own cognitive processes by iterating and reapplying on them-selves the very same cortical operations that they use for the interpretation of signals from the outer world. Search for the neuronal substrate of awareness therefore converges with the search for the cognitive mechanisms through which brains analyze their environment. The hypothesis is put forward that the mammalian brain generates continuously highly dynamic states that, when modulated by input signals, rapidly converge towards points of transient stability that correspond to the respective input constellation. It is proposed that these states are characterized by the dynamic binding of feature-specific cells into functionally coherent cell assemblies which as a whole represent the constellation of features defining a particular perceptual object. Arguments are presented that favor the notion that the cognitive operations supporting awareness consist of an iteration of such dynamic binding processes which then lead to the formation of higher-order assemblies that correspond to the contents of conscious awareness. Experimental data are reviewed relating to the questions of how assemblies are formed and which signatures define the relations among the responses of distributed neurons. It is argued that assemblies self-organize through reciprocal interactions of neurons coupled by reentrant loops and that the signature of relatedness consists of the transient synchronization of the discharges of the respective neurons. Evidence is presented that these synchronization phenomena depend on the same state variables as awareness: Both require for their manifestation activated brain states characterized by desynchronized EEGs. It is concluded that phenomenal awareness is amenable to neurobiological reductionism; but it is also proposed that self-consciousness requires a different explanatory approach because it emerges from the dialogue between different brains and hence has the quality of a cultural construct.

Animals↗
PubMed2001

Influence of posture on the Valsalva manoeuvre.

The objective of the present study was to evaluate the influence of posture on the responses of blood pressure (BP) and heart rate (HR) to the Valsalva manoeuvre (VM). Neurohumoral activation, as well as changes in intravascular and intracardiac volumes and pressures, are well known effects of orthostatic stress. These changes are likely to have significant effects on cardiovascular reflexes, such as the response to the VM. However, the influence of posture on the VM has not been intensively evaluated, except for a few studies involving small sex- and age-selected case series. We therefore investigated the effects of posture on the VM in a larger non-selected group of healthy control subjects. In 19 healthy volunteers (ten female/nine male; age range 20-72 years, mean age 43 years), two reproducible VMs (40 mmHg; 15 s) were performed after 10 min of supine rest, 10 min of sitting and 10 min of standing. HR and BP were monitored continuously. End-diastolic volume, total peripheral resistance and cardiac output were calculated at baseline for each position. We found that assuming an upright position resulted in increases in total peripheral resistance and HR, accompanied by decreases in end-diastolic volume and cardiac output. The fall in BP during early phase II and the BP overshoot during phase IV were clearly more pronounced with increasing orthostatic stress, whereas the rise in BP during late phase II remained unchanged; pulse pressure was more compressed during phase II, but higher during phase IV. The Valsalva ratio was not significantly affected, but baroreflex gain (calculated from early phase II) was significantly decreased in the upright position. While a reduced late phase II was observed on one occasion in each of the lying and sitting positions, three abnormal responses were observed during standing. We conclude that posture has a significant influence on BP responses to the VM, probably resulting from changes in the intrathoracic blood volume. Standing results in a lower rate of 'flat-top' responses, but also seems to reduce the specificity of this test. Sympathetic activation in the upright position seems to blunt baroreflexes, leading to similar HR responses in spite of larger changes in BP.

Adult↗
PubMed2000

Splanchnic-mesenteric capacitance bed in the postural tachycardia syndrome (POTS).

BACKGROUND: Gastroenterologic symptoms are common in the postural tachycardia syndrome (POTS), and postprandial worsening of orthostatic symptoms often occurs. We, therefore, investigated splanchnic-mesenteric vasoregulation in POTS. SUBJECTS AND METHODS: Eleven patients with POTS (one man, 10 women, 29.4 +/- 7.7 (S.D.) years) and 10 controls (two men, eight women, 27.9 +/- 5.6 years) participated in this study. The protocol included 5 min of 70 degrees head-up tilt (HUT) before and after a liquid meal, as well as 1.5 min of hyperventilation. Blood pressure (BP), heart rate (HR), endtidal CO2, and cardiovascular indices derived from thoracic electrical bioimpedance were continuously monitored. Superior mesenteric artery (SMA) blood flow was measured by real time Doppler ultrasound and analyzed off-line. Cross-sectional area of SMA (SMA-area) and time-averaged velocity (SMA-TAV) were measured; SMA blood flow (SMA-BF) and vascular resistance (SMA-VR) were derived. RESULTS: The following significant results were found: at supine rest, the POTS group had higher HR, BP, SMA-TAV and SMA-BF and a lower SMA-VR than the control group. HUT resulted in a reduction of pulse pressure, CO2 level, SMA-area, SMA-TAV and SMA-VF and increment of HR and SMA-VR in both groups. The POTS group underwent greater increment of HR and greater reduction of CO2 than controls. Hyperventilation induced increment of HR and cardiac index (CI) and reduction of SMA-VR in controls; no significant change occurred in POTS. The test meal induced increments of HR, CI, SMA-area, SMA-TAV and SMA-VF and reduction of SMA-VR in patients and controls for both supine rest and HUT. CONCLUSION: The main novel observations of increased resting SMA-BF, SMA-TAV supine, and reduced SMA-VR when compared with controls support the notion that there is excessive splanchnic capacity (pooling) at rest in POTS.

Adult↗
PubMed2000

Interhemispheric asymmetries of the modular structure in human temporal cortex.

Language-relevant processing of auditory signals is lateralized and involves the posterior part of Brodmann area 22. We found that the functional lateralization in this area was accompanied by interhemispheric differences in the organization of the intrinsic microcircuitry. Neuronal tract tracing revealed a modular network of long-range intrinsic connections linking regularly spaced clusters of neurons. Although the cluster diameter was similar in both hemispheres, their spacing was about 20 percent larger in the left hemisphere. Assuming similar relations between functional and anatomical architecture as in visual cortex, the present data suggest that more functionally distinct columnar systems are included per surface unit in the left than in the right area 22.

Adult↗
PubMed2000

Neural synchrony correlates with surface segregation rules.

To analyse an image, the visual system must decompose the scene into its relevant parts. Identifying distinct surfaces is a basic operation in such analysis, and is believed to precede object recognition. Two superimposed gratings moving in different directions (plaid stimuli) may be perceived either as two surfaces, one being transparent and sliding on top of the other (component motion) or as a single pattern whose direction of motion is intermediate to the component vectors (pattern motion). The degree of transparency, and hence the perception, can be manipulated by changing only the luminance of the grating intersections. Here we show that neurons in two visual cortical areas--A18 and PMLS--synchronize their discharges when responding to contours of the same surface but not when responding to contours belonging to different surfaces. The amplitudes of responses correspond to previously described rate predictions for component and pattern motion, but, in contrast to synchrony, failed to reflect the transition from component to pattern motion induced by manipulating the degree of transparency. Thus, dynamic changes in synchronization could encode, in a context-dependent way, relations among simultaneous responses to spatially superimposed contours and thereby bias their association with distinct surfaces.

Animals↗
PubMed2000

Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex.

In the present study we examine the influence of neurotrophins on experience-dependent synaptic rearrangement in developing and adult visual cortex. Brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) was continuously infused into cortical area 18, and the functional architecture of the cortex was examined by use of optical and electrophysiological recording techniques. In kittens, BDNF infusion during monocular deprivation (MD) reversed the normally occurring ocular dominance (OD) shift towards the non-deprived eye so that the deprived eye dominated the BDNF-treated cortex after MD. Under conditions of equal activation of thalamocortical synapses, i.e. when animals were either subject to binocular deprivation (BD) or reared without deprivation, BDNF infusion did not disrupt binocularity of cortical units, but reversed the natural OD bias towards the contralateral eye in favour of the ipsilateral eye. In addition, BDNF treatment in kittens led to a loss of the orientation selectivity of cortical units irrespective of rearing conditions. In adult animals, BDNF influenced neither OD distributions nor orientation selectivity. The effect of NGF was markedly different. It was ineffective in kittens but in adult animals it caused a shift of OD towards the deprived eye when MD was combined with NGF infusion. However, in this case orientation selectivity was preserved. Thus, both neurotrophins have profound activity- and age-dependent effects on the functional architecture of the visual cortex. Moreover, our results indicate that simple substitution of neurotrophins in excess is unlikely to compensate for deprivation effects by preserving or restoring the normal functional architecture of the cortex.

Age Factors↗