Biomedical subjects

Wolf Singer

Publications and source records attributed to Wolf Singer.

At least 19 recordsLinked to original sources

PubMed2006

Brightness induction: rate enhancement and neuronal synchronization as complementary codes.

In cat visual cortex, we investigated with parallel recordings from multiple units the neuronal correlates of perceived brightness. The perceived brightness of a center grating was changed by varying the orientation or the relative spatial phase of a surrounding grating. Brightness enhancement by orientation contrast is associated with an increase of discharge rates of responses to the center grating but not with changes in spike synchronization. In contrast, if brightness enhancement is induced by phase offset, discharge rates are unchanged but synchronization increases between neurons responding to the center grating. The changes in synchronization correlate well with changes in perceived brightness that were assessed in parallel in human subjects using the same stimuli. These results indicate that in cerebral cortex the modulation of synchronicity of responses is used as a mechanism complementary to rate changes to enhance the saliency of neuronal responses.

Action Potentials↗

PubMed2006

Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology.

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, novel methods of time series analysis have been developed for the examination of task- and performance-related oscillatory activity and its synchronization. Studies employing these advanced techniques revealed that synchronization of oscillatory responses in the beta- and gamma-band is involved in a variety of cognitive functions, such as perceptual grouping, attention-dependent stimulus selection, routing of signals across distributed cortical networks, sensory-motor integration, working memory, and perceptual awareness. Here, we review evidence that certain brain disorders, such as schizophrenia, epilepsy, autism, Alzheimer's disease, and Parkinson's are associated with abnormal neural synchronization. The data suggest close correlations between abnormalities in neuronal synchronization and cognitive dysfunctions, emphasizing the importance of temporal coordination. Thus, focused search for abnormalities in temporal patterning may be of considerable clinical relevance.

Alzheimer Disease↗

PubMed2006

See globally, spike locally: oscillations in a retinal model encode large visual features.

We show that coherent oscillations among neighboring ganglion cells in a retinal model encode global topological properties, such as size, that cannot be deduced unambiguously from their local, time-averaged firing rates. Whereas ganglion cells may fire similar numbers of spikes in response to both small and large spots, only large spots evoke coherent high frequency oscillations, potentially allowing downstream neurons to infer global stimulus properties from their local afferents. To determine whether such information might be extracted over physiologically realistic spatial and temporal scales, we analyzed artificial spike trains whose oscillatory correlations were similar to those measured experimentally. Oscillatory power in the upper gamma band, extracted on single-trials from multi-unit spike trains, supported good to excellent size discrimination between small and large spots, with performance improving as the number of cells and/or duration of the analysis window was increased. By using Poisson distributed spikes to normalize the firing rate across stimulus conditions, we further found that coincidence detection, or synchrony, yielded substantially poorer performance on identical size discrimination tasks. To determine whether size encoding depended on contiguity independent of object shape, we examined the total oscillatory activity across the entire model retina in response to random binary images. As the ON-pixel probability crossed the percolation threshold, which marks the sudden emergence of large connected clusters, the total gamma-band activity exhibited a sharp transition, a phenomena that may be experimentally observable. Finally, a reanalysis of previously published oscillatory responses from cat ganglion cells revealed size encoding consistent with that predicted by the retinal model.

Action Potentials↗

PubMed2006

Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia.

Recent theoretical and empirical research on schizophrenia converges on the notion that core aspects of the pathophysiology of the disorder may arise from a dysfunction in the coordination of distributed neural activity. Synchronization of neural responses in the beta-band (15-30 Hz) and gamma-band range (30-80 Hz) has been implicated as a possible neural substrate for dysfunctional coordination in schizophrenia. To test this hypothesis, we examined the electroencephalography (EEG) activity in 19 patients with a Diagnostic and Statistical Manual of Mental Disorder, edition IV criteria, diagnosis of schizophrenia and 19 healthy control subjects during a Gestalt perception task. EEG data were analyzed for phase synchrony and induced spectral power as an index of neural synchronization. Schizophrenia patients were impaired significantly in the detection of images that required the grouping of stimulus elements into coherent object representations. This deficit was accompanied by longer reaction times in schizophrenia patients. Deficits in Gestalt perception in schizophrenia patients were associated with reduced phase synchrony in the beta-band (20-30 Hz), whereas induced spectral power in the gamma-band (40-70 Hz) was mainly intact. Our findings suggest that schizophrenia patients are impaired in the long-range synchronization of neural responses, which may reflect a core deficit in the coordination of neural activity and underlie the specific cognitive dysfunctions associated with the disorder.

Action Potentials↗

PubMed2006

Gap junctions among dendrites of cortical GABAergic neurons establish a dense and widespread intercolumnar network.

Gap junctions are common between cortical GABAergic interneurons but little is known about their quantitative distribution along dendritic profiles. Here, we provide direct morphological evidence that parvalbumin-containing GABAergic neurons in layer 2/3 of the cat visual cortex form dense and far-ranging networks through dendritic gap junctions. Gap junction-coupled networks of parvalbumin neurons were visualized using connexin36 immunohistochemistry and confocal laser-scanning microscopy (CLSM). The direct correspondence of connexin36-immunopositve puncta and gap junctions was confirmed by examining the same structures in both CLSM and electron microscopy. Single parvalbumin neurons with large somata (> or =200 microm2) formed 60.3 +/- 12.2 (mean +/- SD) gap junctions with other cells whereby these contacts were not restricted to proximal dendrites but occurred at distances of up to 380 microm from the soma. In a Sholl analysis of large-type parvalbumin neurons, 21.9 +/- 7.9 gap junctions were within 50 microm of the soma, 21.7 +/- 7.6 gap junctions in a segment between 50 and 100 microm, 11.2 +/- 4.7 junctions between 100 and 150 microm, and 5.6 +/- 3.6 junctions were in more distal segments. Serially interconnected neurons could be traced laterally in a boundless manner through multiple gap junctions. Comparison to the orientation-preference columns revealed that parvalbumin-immunoreactive cells distribute randomly whereby their large dendritic fields overlap considerably and cover different orientation columns. It is proposed that this dense and homogeneous electrical coupling of interneurons supports the precise synchronization of neuronal populations with differing feature preferences thereby providing a temporal frame for the generation of distributed representations.

Animals↗

PubMed2006

Cerebral correlates of impaired grating perception in individual, psychophysically assessed human amblyopes.

We investigated neuronal correlates of amblyopic deficits resulting from early onset strabismus or anisometropia by monitoring individual responses in retinotopically mapped cortical visual areas with functional magnetic resonance imaging (fMRI) in eight psychophysically assessed adult amblyopes. In lower visual areas (V1/V2), grating stimuli presented to the normal and the amblyopic eye evoked strong cortical responses, while responses to the amblyopic eye were progressively reduced in higher areas on the central visual pathway (V3a/VP; V4/V8; lateral occipital complex, LOC). Selective reduction for high spatial frequency gratings was especially obvious in LOC. This suggests that transmission of activity from the amblyopic eye is increasingly impaired while it is relayed towards higher processing levels. Elevated responses in parts of areas V1 and V2 to monocular stimulation of the amblyopic eye might be related to the spatial and temporal distortions experienced by some amblyopic subjects.

Adult↗

PubMed2006

Neuronal correlates of colour-graphemic synaesthesia: a fMRI study.

Synaesthesia is a perceptual phenomenon in which specific events in one sensory modality induce experiences in another. In colour-graphemic synaesthesia, subjects report colour experiences induced by written letters. Our subjects displayed this type of synaesthesia, as verified by a test of the consistency of the perceptual associations over time, and had no history of neurological or psychiatric disorders. We investigated the hypothesis that the synaesthetic colour experience is accompanied by an activation of the human colour area (V4/V8) using functional magnetic resonance imaging (fMRI). With retinotopic and colour mapping we could confirm that colour stimuli specifically activate area V4/V8. For the study of colour-graphemic synaesthesia we used an AB boxcar design with blocks of letters that elicited a synaesthetic colour experience (condition A) alternating with blocks of letters that did not (condition B). In both hemispheres condition A led to a significantly higher activation of V4/V8 than condition B. These findings support the hypothesis that the grapheme-induced colour perception in synaesthesia is caused by an activation of the colour areas of the human visual cortex.

Association↗

PubMed2006

Tight covariation of BOLD signal changes and slow ERPs in the parietal cortex in a parametric spatial imagery task with haptic acquisition.

The present study investigated the relation of brain activity patterns measured with functional magnetic resonance imaging (fMRI) and slow event-related potentials (ERPs) associated with a complex cognitive task. A second goal was to examine the neural correlates of spatial imagery of haptically--instead of visually--acquired representations. Using a mental image scanning task, spatial imagery requirements were systematically manipulated by parametrically varying the distance between haptically acquired landmarks. Results showed a close relation between slow ERPs and the blood oxygenation level dependent (BOLD) signal in human parietal lobe. Reaction times of mental scanning correlated with the distances between landmarks on the learned display. In parallel, duration and amplitude of slow ERPs and duration of the haemodynamic response systematically varied as a function of mental scanning distance. Source analysis confirmed that the ERP imagery effect likely originated from the same cortical substrate as the corresponding BOLD effect. This covariation of the BOLD signal with slow ERPs is in line with recent findings in animals demonstrating a tight link between local field potentials and the BOLD signal. The parietal location of the imagery effect is consistent with the idea that externally triggered (perceptual) and mentally driven (imagery) spatial processes are both mediated by the same supramodal brain areas.

Acoustic Stimulation↗

PubMed2005

Hemodynamic signals correlate tightly with synchronized gamma oscillations.

Functional imaging methods monitor neural activity by measuring hemodynamic signals. These are more closely related to local field potentials (LFPs) than to action potentials. We simultaneously recorded electrical and hemodynamic responses in the cat visual cortex. Increasing stimulus strength enhanced spiking activity, high-frequency LFP oscillations, and hemodynamic responses. With constant stimulus intensity, the hemodynamic response fluctuated; these fluctuations were only loosely related to action potential frequency but tightly correlated to the power of LFP oscillations in the gamma range. These oscillations increase with the synchrony of synaptic events, which suggests a close correlation between hemodynamic responses and neuronal synchronization.

Action Potentials↗

PubMed2005

Primary visual cortex activity along the apparent-motion trace reflects illusory perception.

The illusion of apparent motion can be induced when visual stimuli are successively presented at different locations. It has been shown in previous studies that motion-sensitive regions in extrastriate cortex are relevant for the processing of apparent motion, but it is unclear whether primary visual cortex (V1) is also involved in the representation of the illusory motion path. We investigated, in human subjects, apparent-motion-related activity in patches of V1 representing locations along the path of illusory stimulus motion using functional magnetic resonance imaging. Here we show that apparent motion caused a blood-oxygenation-level-dependent response along the V1 representations of the apparent-motion path, including regions that were not directly activated by the apparent-motion-inducing stimuli. This response was unaltered when participants had to perform an attention-demanding task that diverted their attention away from the stimulus. With a bistable motion quartet, we confirmed that the activity was related to the conscious perception of movement. Our data suggest that V1 is part of the network that represents the illusory path of apparent motion. The activation in V1 can be explained either by lateral interactions within V1 or by feedback mechanisms from higher visual areas, especially the motion-sensitive human MT/V5 complex.

Adult↗

PubMed2005

Phase dependent sign changes of GABAergic synaptic input explored in-silicio and in-vitro.

Inhibitory interactions play a crucial role in the synchronization of neuronal activity. Here we investigate the effect of GABAergic PSPs on spike timing in cortical neurons that exhibit an oscillatory modulation of their membrane potential. To this end we combined numerical simulations with in-vitro patch-clamp recordings from layer II/III pyramidal cells of the rat visual cortex. Special emphasis was placed on exploring how the reversal potential of the GABAergic synaptic currents (EGABA) and the phase relations of the PSPs relative to the oscillation cycles affect the timing of spikes riding on the depolarizing peaks of the oscillations. The simulations predicted: (1) With EGABA more negative than the oscillation minima PSPs are hyperpolarizing at all phases and thus delay or prevent spikes. (2) With EGABA being more positive than the oscillation maxima PSPs are depolarizing in a phase-independent way and lead to a phase advance of spikes. (3) In the intermediate case where EGABA lies within oscillation maxima and minima PSPs are either hyper- or depolarizing depending on their phase relations to the V(m) oscillations and can therefore either delay or advance spikes. Experiments conducted in this most interesting last configuration with biphasic PSPs agreed with the model predictions. Additional theoretical investigations revealed the effect of these PSP induced shifts in spike timing on synchronization in neuronal circuits. The results suggest that GABAergic mechanisms can assume highly specific timing functions in oscillatory networks.

Animals↗

PubMed2005

Synaptic plasticity in the absence of backpropagating spikes of layer II inputs to layer V pyramidal cells in rat visual cortex.

Use-dependent changes of synaptic transmission are thought to depend on the evaluation of temporal correlations between pre- and postsynaptic excitatory activity. Previous studies have demonstrated long-term potentiation (LTP) in layer V pyramidal cells after coincident pairing of presynaptic excitatory input with postsynaptic depolarizations, evoking backpropagating action potentials (BAPs). Here we paired excitatory layer II input with somatic hyperpolarization, which blocked BAPs in layer V pyramidal cells of rat visual cortex and induced reliable long-term depression (LTD). Upon cholinergic receptor activation, this BAP-independent protocol also induced LTP, which was not dependent on N-methyl-d-aspartate receptor activation, but blocked by metabotropic glutamate receptor (mGluR) antagonists.

Action Potentials↗

PubMed2004

Short- and long-term effects of cholinergic modulation on gamma oscillations and response synchronization in the visual cortex.

Neurons can engage in synchronized oscillatory activity in the gamma-frequency range when responding to sensory stimuli. Both the oscillatory patterning and the synchronization of responses are enhanced with arousal and attention or when the electroencephalogram is activated by electrical stimulation of the mesencephalic reticular formation. Here we show with intracortical application of cholinergic antagonists that the enhancement of gamma oscillations and response synchronization is mediated by acetylcholine and muscarinic receptors. We demonstrate further that coapplication of cholinergic agonists with synchrony-inducing light stimuli causes a lasting increase in the probability that the stimulated cells engage in gamma oscillations and response synchronization. These changes develop slowly over tens of minutes and then persist for many hours. Thus, cholinergic modulation plays a crucial role both in the fast, state-dependent facilitation of gamma oscillations and response synchronization and in use-dependent long-term modifications of cortical dynamics that favor synchronization of responses in the gamma-frequency range.

Action Potentials↗

PubMed2004

Phase sensitivity of synaptic modifications in oscillating cells of rat visual cortex.

Synaptic modifications depend on the amplitude and temporal relations of presynaptic and postsynaptic activation. The interactions among these variables are complex and hard to predict when neurons engage in synchronized high-frequency oscillations in the beta and gamma frequency range, as is often observed during signal processing in the cerebral cortex. Here we investigate in layer II/III pyramidal cells of rat visual cortex slices how synapses change when synchronized, oscillatory multifiber activity impinges on postsynaptic neurons during membrane potential (V(m)) oscillations at 20 and 40 Hz. Synapses underwent long-term potentiation (LTP) when EPSPs coincided with the peaks of the V(m) oscillations but exhibited long-term depression (LTD) when EPSPs coincided with the troughs. The induction of LTP but not of LTD was NMDA receptor dependent, required additional activation of muscarinic receptors in older animals, and persisted in a kainate-driven increased conductance state. Thus, even when neuronal networks engage in high-frequency oscillations, synaptic plasticity remains exquisitely sensitive to the timing of discharges. This is an essential prerequisite for theories which assume that precise synchronization of discharges serves as signature of relatedness in distributed processing.

Age Factors↗

PubMed2004

Amplitude and direction of saccadic eye movements depend on the synchronicity of collicular population activity.

Synchronization of neuronal discharges has been observed in numerous brain structures, but opinions diverge regarding its significance in neuronal processing. Here we investigate whether the motion vectors of saccadic eye movements evoked by electrical multisite stimulation of the cat superior colliculus (SC) are influenced by varying the degree of synchrony between the stimulus trains. With synchronous activation of SC sites, the vectors of the resulting saccades correspond approximately to the averages of the vectors of saccades evoked from each site alone. In contrast, when the pulses of trains applied to the different sites are temporally offset by as little as 5-10 ms, the vectors of the resulting saccades come close to the sum of the individual vectors. Thus saccade vectors depend not only on the site and amplitude of collicular activation but also on the precise temporal relations among the respective spike trains. These data indicate that networks within or downstream from the SC discriminate with high temporal resolution between synchronous and asynchronous population responses. This supports the hypothesis that information is encoded not only in the rate of neuronal responses but also in the precise temporal relations between discharges.

Action Potentials↗

PubMed2003

Processing deficits in primary visual cortex of amblyopic cats.

Early esotropic squint frequently results in permanent visual deficits in one eye, referred to as strabismic amblyopia. The neurophysiological substrate corresponding to these deficits is still a matter of investigation. Electrophysiological evidence is available for disturbed neuronal interactions in both V1 and higher cortical areas. In this study, we investigated the modulation of responses in cat V1 to gratings at different orientations and spatial frequencies (SFs; 0.1-2.0 cycles/degrees) with optical imaging of intrinsic signals. Maps evoked by both eyes were well modulated at most spatial frequencies. The layout of the maps resembled that of normal cats, and iso-orientation domains tended to cross adjacent ocular dominance borders preferentially at right angles. Visually evoked potentials (VEPs) were recorded at SFs ranging from 0.1 to 3.5 cycles/degrees and revealed a consistently weaker eye for the majority of squinting cats. At each SF, interocular differences in VEP amplitudes corresponded well with differences in orientation response and selectivity in the maps. At 0.7-1.3 cycles/ degrees, population orientation selectivity was significantly lower for the weaker eye in cats with VEP differences compared with those with no VEP amplitude differences. In addition, the cutoff SF, above which gratings no longer induced orientation maps, was lower for the weaker eye (> or =1.0 cycles/degrees). These data reveal a close correlation between the loss of visual acuity in amblyopia as assessed by VEPs and the modulation of neuronal activation as seen by optical imaging of intrinsic signals. Furthermore, the results indicate that amblyopia is associated with altered intracortical processing already in V1.

Amblyopia↗

PubMed2003

Precise placement of multiple electrodes into functionally predefined cortical locations.

Current research on topics such as effective connectivity, neuronal coding strategy or signal propagation in the central nervous system requires simultaneous recordings from multiple sites within functionally grouped but topologically distributed neuronal clusters. We have addressed this issue by characterization of the cortical functional architecture using optical imaging of intrinsic signals (OI) and subsequent placement of multiple, individually adjustable electrodes into pre-selected domains. In order to achieve maximum precision and flexibility for the positioning of electrodes, a plastic cylinder containing channels of an extremely high aspect ratio (density >20 channels/mm(2)) was fixed above the cortex and individual channel positions were superimposed onto the functional maps of orientation columns obtained previously with OI. Subsequently, channels corresponding to the desired locations in the functional map were used as guide tubes for electrode insertion. The spatial precision of this approach was in the range of 100 microm and experiments in cat primary visual cortex revealed a close correlation between the desired and the actually recorded orientation preferences of the targeted columns. The method is applicable to all cortical areas in which OI is feasible and offers a high degree of flexibility with respect to the number and geometry of applicable probes. It is, thus, an excellent tool for studying distributed codes and interactions between multiple predefined recording sites.

Animals↗

PubMed2003

Features of neuronal synchrony in mouse visual cortex.

Synchronization of neuronal discharges has been hypothesized to play a role in defining cell assemblies representing particular constellations of stimulus features. In many systems and species, synchronization is accompanied by an oscillatory response modulation at frequencies in the gamma-band. The cellular mechanisms underlying these phenomena of synchronization and oscillatory patterning have been studied mainly in vitro due to the difficulty in designing a direct in vivo assay. With the prospect of using conditional genetic manipulations of cortical network components, our objective was to test whether the mouse would meet the criteria to provide a model system for the study of gamma-band synchrony. Multi-unit and local field potential recordings were made from the primary visual cortex of anesthetized C57BL/6J mice. Neuronal responses evoked by moving gratings, bars, and random dot patterns were analyzed with respect to neuronal synchrony and temporal patterning. Oscillations at gamma-frequencies were readily evoked with all types of stimuli used. Oscillation and synchronization strength were largest for gratings and decreased when the noise level was increased in random-dot patterns. The center peak width of cross-correlograms was smallest for bars and increased with noise, yielding a significant difference between coherent random dot patterns versus patterns with 70% noise. Field potential analysis typically revealed increases of power in the gamma-band during response periods. Our findings are compatible with a role for neuronal synchrony in mediating perceptual binding and suggest the usefulness of the mouse model for testing hypotheses concerning both the mechanisms and the functional role of temporal patterning.

Action Potentials↗