Rüdiger Wenzel

Spontaneous low frequency oscillations of cerebral hemodynamics and metabolism in human adults.

UNLABELLED We investigated slow spontaneous oscillations in cerebral oxygenation in the human adults 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.

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.

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.

Noninvasive Assessment of Changes in Cytochrome-c Oxidase Oxidation in Human Subjects during Visual Stimulation:

In this study the authors used a whole-spectrum near-infrared spectroscopy approach to noninvasively assess changes in hemoglobin oxygenation and cytochrome-c oxidase redox state (Cyt-Ox) in the occipital cortex during visual stimulation. The system uses a white light source (halogen lamp). The light reflected from the subjects head is spectrally resolved by a spectrograph and dispersed on a cooled charge-coupled device camera. The authors showed the following using this approach: (1) Changes in cerebral hemoglobin oxygenation (increase in concentration of oxygenated hemoglobin, decrease in concentration of deoxygenated hemoglobin) in the human occipital cortex during visual stimulation can be assessed quantitatively. (2) The spectral changes during functional activation cannot be completely explained by changes in hemoglobin oxygenation solely; Cyt-Ox has to be included in the analysis. Only if Cyt-Ox is considered can the spectral changes in response to increased brain activity be explained. (3) Cytochrome-c oxidase in the occipital cortex of human subjects is transiently oxidized during visual stimulation. This allows us to measure vascular and intracellular energy status simultaneously.

Saccadic Suppression Induces Focal Hypooxygenation in the Occipital Cortex

This study investigated how a decrease in neuronal activity affects cerebral blood oxygenation employing a paradigm of acoustically triggered saccades in complete darkness. Known from behavioral evidence as saccadic suppression, electrophysiologically it has been shown in monkeys that during saccades an attenuation of activity occurs in visual cortex neurons (Duffy and Burchfiel, 1975). In study A, using blood oxygen level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI), the authors observed signal intensity decreases bilaterally at the occipital pole during the performance of saccades at 2 Hz. In study B.1, the authors directly measured changes in deoxyhemoglobin [deoxy-Hb] and oxyhemoglobin [oxy-Hb] concentration in the occipital cortex with near-infrared spectroscopy (NIRS). Whereas a rise in [deoxy-Hb] during the performance of saccades occurred, there was a drop in [oxy-Hb]. In a second NIRS study (B.2), subjects performed saccades at different rates (1.6, 2.0, and 2.3 Hz). Here the authors found the increase in deoxy-Hb and the decrease of oxy-Hb to be dependent on the frequency of the saccades. In summary, the authors observed a focal hypooxygenation in the human visual cortex dependent on the saccade-frequency in an acoustically triggered saccades paradigm. This could be interpreted as evidence that corresponding to the focal hyperoxygenation observed in functional brain activation, caused by an excessive increase in cerebral blood flow (CBF) over the increase in CMRO2 during decreased neuronal activity CBF, is more reduced than oxygen delivery.

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.

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.

Proprioceptive head posture-related processing in human polysensory cortical areas.

Besides visual input and vestibular afferents, proprioceptive input from muscle spindle receptors of the neck region contributes to the perception of egocentric space. Using fMRI we performed a neck muscle vibration paradigm in humans in order to detect brain areas involved in processing changes of the head position in relation to the rest of the body. We identified a network of primary and secondary cortical areas: (I) regions that presumably receive direct proprioceptive thalamic input such as areas 3a, 2, S2 and the parieto-insular vestibular cortex (PIVC), (II) foci in the intraparietal sulcus, motor and premotor areas, and the frontal eye field (FEF). Activation of the former reflect early stages of proprioceptive processing, nevertheless these areas contain polysensory subdivisions such as area 3aNv, which also receives vestibular afferents. Together with area PIVC and the vestibular field in area 2 (2v), area 3aNv constitutes the inner vestibular circuit, an interconnected cortical triangle of polysensory areas that project to the posterior parietal cortex (PPC), which is known to be involved in polysensory integration. With respect to possible analogies in the monkey, we speculate that the activation we observed in the PPC is closely related to the LIP and VIP regions of the macaque.

What happens in between? Human oscillatory brain activity related to crossmodal spatial cueing

Previous studies investigated the effects of crossmodal spatial attention by comparing the responses to validly versus invalidly cued target stimuli. Dynamics of cortical rhythms in the time interval between cue and target might contribute to cue effects on performance. Here, we studied the influence of spatial attention on ongoing oscillatory brain activity in the interval between cue and target onset. In a first experiment, subjects underwent periods of tactile stimulation (cue) followed by visual stimulation (target) in a spatial cueing task as well as tactile stimulation as a control. In a second experiment, cue validity was modified to be 50%, 75%, or else 25%, to separate effects of exogenous shifts of attention caused by tactile stimuli from that of endogenous shifts. Tactile stimuli produced: 1) a stronger lateralization of the sensorimotor beta-rhythm rebound (15–22 Hz) after tactile stimuli serving as cues versus not serving as cues; 2) a suppression of the occipital alpha-rhythm (7–13 Hz) appearing only in the cueing task (this suppression was stronger contralateral to the endogenously attended side and was predictive of behavioral success); 3) an increase of prefrontal gamma-activity (25–35 Hz) specifically in the cueing task. We measured cue-related modulations of cortical rhythms which may accompany crossmodal spatial attention, expectation or decision, and therefore contribute to cue validity effects. The clearly lateralized alpha suppression after tactile cues in our data indicates its dependence on endogenous rather than exogenous shifts of visuo-spatial attention following a cue independent of its modality.

Haemoglobin Oxygenation Changes During Visual Stimulation in the Occipital Cortex

It has been shown that near-infrared spectroscopy (NIRS) permits the assessment of functional brain activation.8,9,14,21 Four studies were dedicated to the visual system which partly yielded conflicting results.10,11,13,21 Though all studies showed an increase in [oxy-Hb] during visual stimulation using different stimulation paradigms, the changes observed in [deoxy-Hb] were not uniform. Meek et al.13 reported on a decrease in [deoxy-Hb] in 4 of 10 subjects but an increase in the other 6 subjects, while Kato et al.11 and Hoshi et al.10 using photic stimulation of 8 Hz and 10 Hz found an increase in [deoxy-Hb] in their studies. On the other hand, Villringer et al.21 observed a decrease in [deoxy-Hb] during photic stimulation and picture observation, but this included only 3 subjects lacking therefore statistical evaluation. All NIRS-investigators10,11,13,21 localised the optical probes only with respect to external bony landmarks without knowledge of the exact spatial relation of these landmarks to the anatomy of the brain. This could have led to inaccurate positions of the optical probes over the visual cortex as there is a great variability of the calcarine fissure concerning these external landmarks.18 Localising the optical probes individually according to previously acquired 3D MRI, the aim of the current study was to investigate whether there is a consistent, statistically evident pattern of changes in [oxy-Hb] and [deoxy-Hb] during visual stimulation. Furthermore, we investigated if NIRS is able to detect oxygenation changes due to activation of a secondary or prestriate visual area known from studies both in monkeys and humans as area V5 or MT to be sensitive to the submodality “visual motion”.12,19,22,24