Arno Villringer

Human vestibular cortex as identified with caloric stimulation in functional magnetic resonance imaging.

Anatomic and electrophysiological studies in monkeys have yielded a detailed map of cortex areas receiving vestibular afferents. In contrast, comparatively little is known about the cortical representation of the human vestibular system. In this study we applied caloric stimulation and fMRI to further characterize human cortical vestibular areas and to test for hemispheric dominance of vestibular information processing. For caloric vestibular stimulation we used cold nitrogen to avoid susceptibility artifacts induced by water calorics. Right and left side vestibular stimulation was repetitively performed inducing a nystagmus for at least 90 s after the end of the stimulation in all subjects. Only the first 60 s of this nystagmus period was included for statistical analysis and compared with the baseline condition. Activation maps revealed a cortical network with right hemispheric dominance, which in all subjects comprised the temporoparietal junction extending into the posterior insula and, furthermore, the anterior insula, pre- and postcentral gyrus, areas in the parietal lobe, the ventrolateral portion of the occipital lobe, and the inferior frontal gyrus extending into the inferior part of the precentral sulcus. In conclusion, caloric stimulation in fMRI reveals a widespread cortical network involved in vestibular signal processing corresponding to the findings from animal experiments and previous functional imaging studies in humans. Furthermore, this study demonstrates a strong right hemispheric dominance of vestibular cortex areas regardless of the stimulated side, consistent with the current view of a rightward asymmetrical cortical network for spatial orientation.

Assessment of Local Brain Activation

In five healthy human subjects, near-infrared spectroscopy (NIRS) and positron emission tomography (PET) examinations were performed simultaneously. Changes in [oxy-Hb], [deoxy-Hb] and [total-Hb] as measured by NIRS over the left forehead were compared to measurements of cerebral blood flow by PET during rest and during performance of a calculation task and a Stroop task. When a penetration depth of near-infrared light 0.9 cm into the brain cortex was assumed, a statistically significant correlation between changes in CBF and changes in [total-Hb] was found. These data confirm the validity of NIRS measurements in human adults.

Imaging of leukocytes within the rat brain cortex in vivo

Confocal laser scanning microscopy was used in a rat closed cranial window preparation in order to study rhodamin 6G-labeled leukocytes within the brain cortex in vivo. Leukocytes were visualized up to 150 microns beneath the rat brain surface in noninvasive optical sections. In pial venules, leukocytes were seen flowing with the blood stream, rolling along or sticking to the endothelium, and migrating through the vessel wall. Within cerebral capillaries, leukocyte flux, velocities, and leukocyte plugging were measured. After additional intravenous administration of fluorescein, the plasma, leukocytes, and erythrocytes were visualized simultaneously. Based on stacks of optical sections of fluorescein-labeled capillaries, the individual capillaries were localized within the three-dimensional microvascular network. The usefulness of this technique was illustrated in a feasibility study in which leukocyte sticking to the vascular walls of venules, leukocyte extravasation, and intracapillary leukocyte plugging were monitored in a model of global cerebral ischemia.

In-vivo confocal scanning laser microscopy of the cerebral microcirculation

Confocal scanning laser microscopy (CSLM) was used to study the microcirculation of the brain neocortex in anaesthetized rats. After removal of the dura mater, implantation of a closed cranial window, and intravenous injection of fluorescein, three‐dimensional reconstructions of cortical capillaries were performed down to a depth of 250 μm below the pial surface. Using a one‐dimensional approach (single line scanning), erythrocyte (negative contrast in fluorescently labelled plasma) and leucocyte (labelled with rhodamine 6 G) velocity and supply rate in cortical capillaries were measured. The effect of CO2‐inhalation on capillary blood flow dynamics was studied. Capillaries were imaged continuously for up to 1 h without changes in flow or fluorescence pattern. However, by increasing the laser power 10–100‐fold, aggregate formation was induced and capillaries were occluded, possibly due to damage to vascular endothelium. We conclude that CSLM can be used to study morphological and dynamic aspects of fluorescently labelled subsurface structures in organs of experimental animals.

Noninvasive Assessment of Cerebral Hemodynamics and Tissue Oxygenation during Activation of Brain Cell Function in Human Adults Using Near Infrared Spectroscopy

Near Infrared Spectroscopy (NIRS) was employed to noninvasively and continuously (temporal resolution 0.5 s) assess changes in cerebral hemodynamics and oxygenation during various functional states of the adult human brain. During cognitive stimulation (performing calculations) a frontal increase in local cerebral blood volume and oxygenated hemoglobin concentration was observed in most (10 of 12) subjects. During visual stimulation (observing a picture) this was demonstrated in the occipital region in all three subjects. Deoxygenated hemoglobin either decreased, remained unchanged or slightly increased during these procedures. Epileptic patients were examined during spontaneously occurring complex-partial seizures. During these seizures extremely large increases in blood volume and oxygenated hemoglobin concentration were measured. In conclusion, this feasibility study indicates that NIRS might become a useful and simple bedside tool to assess brain function.

Confocal laser microscopy to study microcirculation on the rat brain surface in vivo

We demonstrate the feasibility of using confocal laser microscopy (CLM) to study the microcirculation on the rat brain surface. Using a closed cranial window model in vivo, microvessels in the size range of capillaries (8 microns) and dynamic events were observed through an intact dura. This study is the first step in the development of a system which simultaneously monitors vascular and metabolic processes using CLM.

Cerebral blood oxygenation changes induced by visual stimulation in humans

We examined local changes of cerebral oxygenation in response to visual stimuli by means of near infrared spectroscopy. A sharply outlined colored moving stimulus which is expected to evoke a broad activation of the striate and prestriate cortex was presented to sixteen healthy subjects. Six of these subjects were also exposed to a colored stationary and a gray stationary stimulus. In two subjects the colored moving stimulus was tested against the colored stationary with an optode position presumably over area V5/MT. As a control condition, subjects performed a simple finger opposition task. Since the calcarine fissure varies greatly with respect to bony landmarks, optodes were positioned individually according to 3-D reconstructed magnetic resonance imaging (MRI). Concentration changes in oxyhemoglobin ([oxy-Hb]) and deoxyhemoglobin ([deoxy-Hb]) were continuously monitored with a temporal resolution of 1 s, using an NIRO 500 (Hamamatsu Photonics, KK, Japan). In response to the visual stimulus, the grand average across all sixteen subjects resulted in a significant increase in [oxy-Hb] of 0.3360.09 arbitrary units (mean6S.E.M.) mirrored by a significant decrease in [deoxy-Hb] of −0.1860.02 arbitrary units, while the motor control condition elicited no significant changes in any parameters. When the near infrared spectroscopy probes were positioned over area V5/MT, the drop of [deoxy-Hb] associated with the moving stimulus was significantly more pronounced than with the stationary stimulus in both subjects examined. No significant differences between the visual stimuli were observed at the optode position close to the calcarine fissure. The oxygenation changes observed in this study are consistent with the pattern we have reported for motor activation. They are in line with physiological considerations and functional MRI studies relying on blood oxygenation level-dependent contrast.

Near-Infrared Spectroscopy in Functional Activation Studies

Near infrared spectroscopy (NIRS) has recently been used in functional activation studies as a non-invasive tool to monitor changes in cerebral oxygenation in human adults1–6. If NIRS is to establish its place in functional brain research it must be proven that the changes monitored reflect the activation state of the cortex in response to a stimulus. This article gives an overview of the studies performed. On the basis of the reported findings and results from two studies by our own group7,8 a description of the typical NIRS response pattern over an activated cortical area is attempted.

A software tool for interactive exploration of intrinsic functional connectivity opens new perspectives for brain surgery

BackgroundFunctional connectivity analysis of resting-state functional magnetic resonance imaging data (fcrs-fMRI) has been shown to be a robust non-invasive method for localization of functional networks (without using specific tasks) and to be promising for presurgical planning. However, in order to transfer the approach to everyday clinical practice, fcrs-fMRI needs to be further validated and made easily accessible to neurosurgeons. This paper addresses the latter by presenting a software tool designed for neurosurgeons for analyzing and visualizing fcrs-fMRI data.MethodsA prototypical interactive visualization tool was developed to enable neurosurgeons to explore functional connectivity data and evaluate its usability. The implementation builds upon LIPSIA, an established software package for the assessment of functional neuroimaging data, and integrates the selection of a region-of-interest with the computation and visualization of functionally connected areas. The tool was used to explore data from a healthy participant and eight brain lesion patients. The usability of the software was evaluated with four neurosurgeons previously unacquainted with the methodology, who were asked to identify prominent, large-scale cortical networks.FindingsWith this novel tool, previously published findings, such as tumor displacement of the sensorimotor cortex and other disturbances of functional networks, were reproduced. The neurosurgeons were able to consistently obtain results similar to the results of an expert, with the exception of the language network. Immediate feedback helped to pinpoint functional networks quickly and intuitively, with even inexperienced users requiring less than 3 min per network.ConclusionsAlthough fcrs-fMRI is a nascent method still undergoing evaluation with respect to established standards, the interactive software is nonetheless a promising tool for non-invasive exploration of individual functional connectivity networks in neurosurgical practice, both for well-known networks and for those less typically addressed.

Applicability of Laser-Doppler Flowmetry for Cerebral Blood Flow Monitoring in Neurological Intensive Care

Laser Doppler flowmetry (LDF) is a technique for real-time assessment of cerebral blood flow (CBF) changes with potential clinical applicability. Experimental studies have validated that LDF allows accurate measurement of changes in CBF due to physiological and pathophysiological stimuli. Absolute quantitation of flow in ml/100 g min by LDF is not possible. The technique may be used in patients during open brain surgery and postoperatively for bedside CBF monitoring. Disadvantages of the technique are that the flow measurement is highly localized (about 1 mm3) and artifacts may be produced by movement, light or probe placement over large surface vessels. The fibre optic probes for LDF are small enough to be introduced into routinely used intraventricular pressure catheters. We suggest that simultaneous monitoring of CBF and intracranial pressure by such a device holds promise for improved management of patients with critical brain injury.