[Study patients recover better from stroke. L-dopa: doping for the apolpexy brain? (interview by Waldtraud Paukstadt].
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Clinical Trials as Topic↗
Biomedical subjects
A Villringer
Publications and source records attributed to A Villringer.
Linear aspects of changes in deoxygenated hemoglobin concentration and cytochrome oxidase oxidation during brain activation.
We used near infrared spectroscopy (NIRS) to investigate the vascular and metabolic response to brain activation in human primary and adjacent secondary visual cortex. NIRS is able to measure concentration changes in deoxygenated hemoglobin ([deoxy-Hb]) (which mainly contribute to the blood oxygenation level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI)) as well as concentration changes of oxygenated hemoglobin ([oxy-Hb]) and corpuscular blood volume ([total-Hb] = [oxy-Hb] + [deoxy-Hb]) and changes in the redox status of the cytochrome c oxidase ([Cyt-Ox]), a putative parameter for cellular oxygenation. A sound understanding of the transfer functions between stimulus parameters, neuronal activity, and vascular/metabolic parameters is important for interpretation of data acquired with indirect neuroimaging techniques like fMRI, especially in event-related design studies. In the present study we tested whether the vascular/metabolic response to stimulation can be described as a linear and time invariant system. Since linearity is a property attributed to systems that satisfy the scaling and superposition properties, as a first simple test, superposition of the responses obtained from short duration visual stimuli was used to predict the responses of longer duration stimuli. Our results showed that the predictions of [deoxy-Hb] and [Cyt-Ox] responses to stimuli of 6- to 24-s duration were satisfactory whereas predictions of [oxy-Hb] and [total-Hb] were insufficient. In a second step, a calculated convolution function of an assumed impulse response function and the stimulus function was fitted with the measured [deoxy-Hb] and [Cyt-Ox] curves to obtain amplitude, time delay, and time constant parameters. We show that predictions of cellular and vascular oxygenation responses to visual stimulation are good for 6- to 24-s stimuli duration under the assumption of a linear transfer characteristic. This model is not valid for corpuscular volume changes which affect mainly the [oxy-Hb] response. Noninvasive NIRS is shown to be a suitable method to get more direct information about neuronal-activity-associated changes in cerebral parameters which are partly reflected in BOLD signal but are not fully understood yet.
Adult↗
No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation.
Using optical methods through a closed cranial window over the rat primary sensory cortex in chloralose/urethane-anesthetized rats we evaluated the time course of oxygen delivery and consumption in response to a physiological stimulus (whisker deflection). Independent methodological approaches (optical imaging spectroscopy, single fiber spectroscopy, oxygen-dependent phosphorescence quenching) were applied to different modes of whisker deflection (single whisker, full whisker pad). Spectroscopic data were evaluated using different algorithms (constant pathlength, differential pathlength correction). We found that whisker deflection is accompanied by a significant increase of oxygenated hemoglobin (oxy-Hb), followed by an undershoot. An early increase in deoxygenated hemoglobin (deoxy-Hb) proceeded hyperoxygenation when spectroscopic data were analyzed by constant pathlength analysis. However, correcting for the wavelength dependence of photon pathlength in brain tissue (differential pathlength correction) completely eliminated the increase in deoxy-Hb. Oxygen-dependent phosphorescence quenching did not reproducibly detect early deoxygenation. Together with recent fMRI data, our results argue against significant early deoxygenation as a universal phenomenon in functionally activated mammalian brain. Interpreted with a diffusion-limited model of oxygen delivery to brain tissue our results are compatible with coupling between neuronal activity and cerebral blood flow throughout stimulation, as postulated 110 years ago by C. Roy and C. Sherrington (1890, J. Physiol. 11:85--108).
Animals↗
In vivo assessment of human visual system connectivity with transcranial electrical stimulation during functional magnetic resonance imaging.
Functional magnetic resonance imaging (fMRI) was used to investigate local and distant cerebral activation induced by transcranial electrical stimulation in order to noninvasively map functional connectivity in the human visual system. Stimulation with lateromedially directed currents and the anode 4.5 cm dorsally to the inion over the right visual cortex induced phosphenes extending into the contralateral lower quadrant of the visual field. fMRI showed a focal hemodynamic response underneath the anode in extrastriate cortex and distant coactivation in subcortical (lateral geniculate nucleus), cortical visual (striate and extrastriate), and visuomotor areas (frontal and supplementary eye fields). This pattern of activation resembles a network of presumably interconnected visual and visuomotor areas. Analysis of activation sites supplies new information about cerebral correlates of phosphenes and shows that the cortical region underneath the cranial stimulation site is not necessarily the origin of behavioral and/or perceptual effects of transcranial stimulation. We conclude that combining transcranial electrical stimulation of neural tissue with simultaneous fMRI offers the possibility to study noninvasively cerebral connectivity in the human brain.
Adult↗
Perfusion and diffusion magnetic resonance imaging in human cerebral venous thrombosis.
BACKGROUND: Diagnosis of cerebral venous thrombosis (CVT) is usually achieved by digital subtraction angiography or magnetic resonance angiography, while structural brain tissue damage can be assessed by computed tomography or magnetic resonance imaging (MRI). Using perfusion and diffusion weighted imaging (PWI, DWI) we aimed in this study to identify pathophysiological patterns corresponding to only functional and hence reversible tissue involvement. METHODS: PWI, DWI, and conventional MRI were performed in six CVT patients acutely and after 16-26 days when their clinical condition had improved. All patients were treated with partial thromboplastin time-effective intravenous heparin. After intravenous administration of a paramagnetic contrast agent, bolus track PWI allows pixel based determination of mean transit time (MTT) and cerebral blood volume (CBV). DWI was performed with two different b values (0, 1000 s/mm2) for calculation of apparent diffusion coefficient (ADC) maps. RESULTS: In five of six cases increased MTT values were observed initially, whereas the CBV was normal, indicating a reduction of cerebral blood flow. ADC values were normal. On follow up after clinical recovery MTT prolongations had resolved. Areas with prolonged MTT did not evolve into structural lesions. CONCLUSION: In patients with CVT, prolongations of MTT in the absence of changes in CBV and ADC seem to indicate reversible involvement of brain tissue, a situation corresponding to the ischaemic penumbra.
Adult↗
Simultaneous near-infrared spectroscopy monitoring of left and right occipital areas reveals contra-lateral hemodynamic changes upon hemi-field paradigm.
In this study we have shown that in humans it is possible to monitor non-invasively and simultaneously both hemispheres revealing cortical oxygenation changes in the occipital area in response to a contra-lateral hemi-field paradigm. A novel multi-channel near infrared spectroscopy approach with a high temporal resolution was used. The results confirm previous findings obtained by functional magnetic resonance imaging and positron emission tomography with the advantage to measure directly not only concentration changes in deoxyhemoglobin as measured by functional magnetic resonance imaging (MRI), but also in oxyhemoglobin with low cost instrumentation potentially useful to investigate the pathophysiology of vision.
Adult↗
Determining changes in NIR absorption using a layered model of the human head.
A theoretical approach is presented to determine absorption changes in different compartments of a layered structure from distributions of times of flight of photons. In addition resulting changes in spatial profiles of time-integrated intensity and mean time of flight are calculated. The capability of a single-distance, time-domain method to determine absorption changes with depth resolution is tested on a layered phantom. We apply this method to in vivo measurements on the human head (motor stimulation, Valsalva manoeuvre) and introduce a small-sized time-domain experimental set-up suitable for bedside monitoring.
Brain↗
Somatotopic organization of human secondary somatosensory cortex.
This fMRI study investigated the human somatosensory system, especially the secondary somatosensory cortex (SII), with respect to its potential somatotopic organization. Eight subjects received electrical stimulation on their right second finger, fifth finger and hallux. Within SII, the typical finding for both fingers was a representation site within the contralateral parietal operculum roughly halfway between the lip of the lateral sulcus and its fundus, whereas the representation site of the hallux was found more medially to this position at the fundus of the lateral sulcus, near the posterior pole of the insula. Somatotopy in SII seems to be less fine-grained than in primary somatosensory cortex (SI), as, in contrast to SI, no separate representations of the two fingers in SII were observed. A similar somatotopic representation pattern between fingers and the hallux was also observed within ipsilateral SII, indicating somatotopy of contra- as well as ipsilateral SII using unilateral stimulation. Further areas exhibiting activation were found in the superior and inferior parietal lobule, in the supplementary and cingulate motor area, and in the insula.
Adult↗
Coagulopathies in ischemic stroke.
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Blood Coagulation Disorders↗
Behavioural relevance modulates access to spatial working memory in humans.
Neurophysiological studies in monkeys suggest selective representation of behaviourally relevant information in working memory. So far, no behavioural evidence for this has been reported for humans. Here, we investigated the role of behavioural relevance for access to human visuospatial working memory by using delayed oculomotor response tasks. Subjects were presented two successive visual cues in different and unpredictable locations while fixating on a central fixation point. After a delay, an unpredictable auditory signal (one beep or two beeps) sounded and the central fixation point was turned off, initiating the oculomotor response (i.e. memory-guided saccade) phase. Two groups of 10 subjects each were studied in two conditions: in the 'relevant' condition, subjects were instructed to memorize both visual cues and to move the eyes to the remembered position of the first cue (one beep) or the second cue (two beeps). The same stimuli were used in the 'irrelevant' condition, but subjects were instructed to memorize and move the eyes to the position of the first cue only, regardless of the second cue and the auditory signal. In the 'relevant' condition, we found a significant increase in errors of memory-guided saccades to the first cue, when the second cue was located between central fixation point and first cue. This spatially selective interference effect disappeared in the 'irrelevant' condition, despite identical stimuli. On a behavioural level, these results show for the first time the significance of behavioural relevance for access to human spatial working memory. These findings complement recent single-neuron studies in monkeys, showing that the neuronal substrates of working memory selectively represent behaviourally relevant perceptual information.
Adult↗
Somatosensory evoked fast optical intensity changes detected non-invasively in the adult human head.
This work is the first to report optical intensity changes (DeltaI/I approximately 0.05%) with a latency between 60 and 160ms after electrical median nerve stimulation at 5Hz detected non-invasively through the intact adult human skull in volunteers. The signal is localised and reproducible when measuring at the same position on successive examinations. Compared to previous reports of fast optical changes in the human adult by a single group (Psychophysiology, 32 (1995) 505) the here reported changes are much smaller. They are in line with results from a photon transport calculation on a head model employing data from exposed cortical tissue. The origin of the signal found here is still unclear, however, they might be the non-invasive equivalent to the scattering changes found in exposed cortical tissue studies (J. Neurophysiol., 78 (1997) 1707).
Adult↗
MRI of small human stroke shows reversible diffusion changes in subcortical gray matter.
Six patients who had suffered small cerebral ischemia affecting subcortical gray matter were examined with diffusion weighted imaging (DWI) and T2-weighted imaging within the first 8 h, during the next 2 days and after 5-16 days. Areas of apparent diffusion coefficient (ADC) decreases were observed acutely and reached the maximum size during the subsequent 2 days. Noticeably, in all subjects, a large portion of the ADC lesion was reversible as judged from the lesion size on final T2 image. The regular reversibility of the ADC decreases in this setting may indicate a hitherto not understood pathophysiological process occurring in small ischemic stroke.
Adult↗
fMRI shows multiple somatotopic digit representations in human primary somatosensory cortex.
Using electrical finger nerve stimulation in normal human subjects, fMRI detected separate representations for all 5 fingers in the primary somatosensory cortex. Responses were located in the posterior wall of the deep central sulcus (most likely corresponding to Brodmann Area (BA) 3b), and the anterior (BA 1) or posterior crown of the postcentral gyrus (BA 2) with rare activations in BA 3a and 4. In BA 3b we found a regular somatotopic mediolateral digit arrangement for fingers 5 to 1 with a mean Euclidean distance of 16 mm between fingers 1 and 5. In contrast BA 1/2 showed a greater number of adjacent activation foci with significantly more overlap and partly even reversed ordering of neighbouring fingers.
Adult↗
Spontaneous low frequency oscillations of cerebral hemodynamics and metabolism in human adults.
UNLABELLED: We investigated slow spontaneous oscillations in cerebral oxygenation in the human adult's visual cortex. The rationale was (1) to demonstrate their detectability by near infrared spectroscopy (NIRS); (2) to analyze the spectral power of as well as the phase relationship between the different NIRS parameters (oxygenated and deoxygenated hemoglobin and cytochrome-oxidase; oxy-Hb/deoxy-Hb/Cyt-ox). Also (3) influences of functional stimulation and hypercapnia on power and phase shifts were investigated. The results show that-in line with the literature-low frequency oscillations (LFO) centred around 0.1 s(-1) and even slower oscillations at about 0.04 s(-1) (very low frequency, VLFO) can be distinguished. Their respective power differs between oxy-Hb, deoxy-Hb, and Cyt-ox. Either frequency (LFO and VLFO) is altered in magnitude by functional stimulation of the cortical area examined. Also we find a change of the phase shift between the vascular parameters (oxy-Hb, tot-Hb) and the metabolic parameter (Cyt-ox) evoked by the stimulation. It is shown that hypercapnia attenuates the LFO in oxy-Hb and deoxy-Hb. CONCLUSIONS: (1) spontaneous vascular and metabolic LFO and VLFO can be reproducibly detected by NIRS in the human adult. (2) Their spectral characteristics and their response to hypercapnia are in line with those described in exposed cortex (for review see (Hudetz et al., 1998)) and correspond to findings with transcranial doppler sonography (TCD) (Diehl et al., 1995) and fMRI (Biswal et al., 1997). (3) The magnitude of and phase relation between NIRS-parameters at the LFO may allow for a local noninvasive assessment of autoregulatory mechanisms in the adult brain.
Adult↗
Near-infrared spectroscopy: does it function in functional activation studies of the adult brain?
Changes in optical properties of biological tissue can be examined by near-infrared spectroscopy (NIRS). The relative transparency of tissues including the skull to near-infrared light is the prerequisite to apply the method to brain research. We describe the methodology with respect to its applicability in non-invasive functional research of the adult cortex. A summary of studies establishing the 'typical' response in NIRS vascular parameters, i.e. changes in the concentration of oxygenated and deoxygenated haemoglobin, over an activated area is followed by the validation of changes in the cytochrome-oxidase redox state in response to a visual stimulus. Proceeding from these findings a rough mapping of this metabolic response over the motion-sensitive extrastriate visual area is demonstrated. NIRS measures concentration changes in deoxygenated haemoglobin [deoxy-Hb] which are assumed to be the basis of fMRI BOLD contrast (blood oxygenation level-dependent). The method is therefore an excellent tool to validate assumptions on the physiological basis underlying the fMRI signal, due to its high specificity as to the parameters measured. Questions concerning the concept of 'activation'/'deactivation' and that of the linearity of the vascular response are discussed. To challenge the method we finally present results from a complex single-trial motor paradigm study testing the hypothesis, that premotor potentials (contingent negative variation) can be examined by functional techniques relying on the vascular response. Some of the work described here has been published elsewhere.
Adult↗
Involvement of the human frontal eye field and multiple parietal areas in covert visual selection during conjunction search.
Searching for a target object in a cluttered visual scene requires active visual attention if the target differs from distractors not by elementary visual features but rather by a feature conjunction. We used functional magnetic resonance imaging (fMRI) in human subjects to investigate the functional neuroanatomy of attentional mechanisms employed during conjunction search. In the experimental condition, subjects searched for a target defined by a conjunction of colour and orientation. In the baseline condition, subjects searched for a uniquely coloured target, regardless of its orientation. Eye movement recordings outside the scanner verified subjects' ability to maintain fixation during search. Reaction times indicated that the experimental condition was attentionally more demanding than the baseline condition. Differential activations between conditions were therefore ascribed to top-down modulation of neural activity. The frontal eye field, the ventral precentral sulcus and the following posterior parietal regions were consistently activated: (i) the postcentral sulcus; (ii) the posterior; and (iii) the anterior part of the intraparietal sulcus; and (iv) the junction of the intraparietal with the transverse occipital sulcus. Parietal regions were spatially distinct and displayed differential amplitudes of signal increase with a maximal amplitude in the posterior intraparietal sulcus. Less consistent activation was found in the lateral fusiform gyrus. These results suggest an involvement of the human frontal eye field in covert visual selection of potential targets during search. These results also provide evidence for a subdivision of posterior parietal cortex in multiple areas participating in covert visual selection, with a major contribution of the posterior intraparietal sulcus.
Adult↗
Physical model for the spectroscopic analysis of cortical intrinsic optical signals.
We used Monte Carlo simulations and the diffusion approximation to estimate correction terms for the analysis of reflectance spectra of cortical intrinsic optical signals. These corrections depend on scattering and absorption properties, i.e. they are dependent on assumptions on the tissue blood content and oxygen saturation. The analysis was applied to reflectance spectra acquired during whisker barrel stimulation in the rat where attenuation spectra were converted to changes in oxygenated and deoxygenated haemoglobin concentration. The description of the experimental data as judged by the residual and sensitivity to variations of wavelength was considerably improved when the correction terms were included. Inclusion of the correction does have a considerable impact on the time course of deoxyhaemoglobin concentration changes. In contrast to the calculation without correction terms, there is no indication for an early increase in deoxyhaemoglobin ('early dip'). This finding might further current interpretation of the coupling between neuronal activation and oxygen extraction and supply.
Absorption↗
Noninvasive functional imaging of human brain using light.
Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatio-temporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring.
Adult↗