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Hellmuth Obrig

Publications and source records attributed to Hellmuth Obrig.

18 recordsLinked to original sources
PubMed2006

The processing of prosody: Evidence of interhemispheric specialization at the age of four.

Beyond its multiple functions in language comprehension and emotional shaping, prosodic cues play a pivotal role for the infant's amazingly rapid acquisition of language. However, cortical correlates of prosodic processing are largely controversial, even in adults, and functional imaging data in children are sparse. We here use an approach which allows to experimentally determine brain activations correlating to the perception and processing of sentence prosody during childhood. In 4-year-olds, we measured focal brain activation using near-infrared spectroscopy and demonstrate that processing prosody in isolation elicits a larger right fronto-temporal activation whereas a larger left hemispheric activation is elicited by the perception of normal language with full linguistic content. Hypothesized by the dual-pathway-model, the present data provide experimental evidence that in children specific language processes rely on interhemispheric specialization with a left hemispheric dominance for processing segmental (i.e. phonological) and a right hemispheric dominance for processing suprasegmental (i.e. prosodic) information. Generally in accordance with the imaging data reported in adults, our finding underlines the notion that interhemispheric specialization is a continuous process during the development of language.

Brain↗
PubMed2006

Synchronization between background activity and visually evoked potential is not mirrored by focal hyperoxygenation: implications for the interpretation of vascular brain imaging.

We performed an electroencephalography and optical topography study simultaneously exploring electrophysiological and vascular response magnitude as a function of stimulus frequency. To elicit a response in the visual cortex, subjects were exposed to flicker frequencies varying from 1 to 25 Hz (1 Hz steps, eyes closed). Extending the standard view to compare magnitudes of the evoked neuronal to the evoked vascular response, we additionally investigated modulations of alpha-power, a marker of "background" EEG activity. The results show two discrepancies between the electrophysiological and vascular response: (1) VEP and alpha-power exhibit a discontinuous peak when stimulating at the individual alpha-frequency (IAF) (approximately 10-11 Hz), indicating resonance between background oscillations and evoked response; this is not mirrored by the vascular response. (2) The vascular response, in contrast, steadily increases up to a maximum at 7-8 Hz and slightly decreases with higher frequencies. This continuous frequency dependence is partly reflected by the decrease in alpha-power up to frequencies of 8-9 Hz and a slight increase in alpha-power beyond the IAF resonance. Although indicating an inverse relationship between alpha-power and vascular response, the frequency dependence of the evoked response does not show such a correlation. Thus, electrophysiological resonance between an individual's alpha-frequency and isofrequent stimulation is not mirrored by the vascular response. Also, spontaneous background EEG activity is an important modulator of the vascular response magnitude. We discuss these deviations from a simple one-to-one translation between evoked potential and vascular response amplitude in the light of questions concerning synchronization, attenuation, and induction of background oscillations such as the alpha-rhythm.

Adolescent↗
PubMed2006

Illuminating the BOLD signal: combined fMRI-fNIRS studies.

Functional magnetic resonance imaging (fMRI) is currently combined with electrophysiological methods to identify the relationship between neuronal activity and the blood oxygenation level-dependent (BOLD) signal. Several processes like neuronal activity, synaptic activity, vascular dilation, blood volume and oxygenation changes underlie both response modalities, that is, the electrophysiological signal and the vascular response. However, accessing single process relationships is absolutely mandatory when aiming at a deeper understanding of neurovascular coupling and necessitates studies on the individual building blocks of the vascular response. Combined fMRI and functional near-infrared spectroscopy studies have been performed to validate the correlation of the BOLD signal to the hemodynamic changes in the brain. Here we review the current status of the integration of both technologies and judge these studies in the light of recent findings on neurovascular coupling.

Blood Volume↗
PubMed2006

Relevance of depth resolution for cerebral blood flow monitoring by near-infrared spectroscopic bolus tracking during cardiopulmonary bypass.

OBJECTIVE: Noninvasive near-infrared spectroscopy (NIRS) is increasingly used to monitor cerebral oxygenation and blood flow status, which is also of high relevance during cardiovascular surgical interventions with cardiopulmonary bypass. Contamination of the cerebral signal by contamination from overlaying extracerebral tissue, however, has been proposed to reduce sensitivity and cerebral selectivity of this promising technique. METHODS: We evaluated a novel depth-resolved approach for the determination of cerebral hemodynamics by near-infrared spectroscopic tracking of intravenously administered indocyanine green boluses. A frequency domain technique was applied, allowing simultaneous determination of light absorption changes and time of flight of single photons and enabling the differentiation between extracerebral and intracerebral tracer kinetics. Depth-resolved near-infrared spectroscopy was tested in 4 patients undergoing cardiopulmonary bypass and compared with data derived by conventional continuous-wave near-infrared spectroscopy. RESULTS: Depth resolution extracted the differential responses of extracerebral and intracerebral blood vessels from near-infrared bolus tracking signals. Postoperative blood flow indices derived from the intracerebral time course exceeded preoperative values by 1.5 +/- 0.2 times, indicating a significant increase of cerebral blood flow not detectable by conventional near-infrared spectroscopy. CONCLUSION: The depth-resolved approach provides additional and relevant data for the interpretation of intraoperative cerebral perfusion during cardiothoracic surgery. The validity of this approach for patients with preexisting risk factors for cerebral hypoperfusion remains to be determined in larger clinical trials.

Aged↗
PubMed2005

The fast optical signal--robust or elusive when non-invasively measured in the human adult?

Near infrared spectroscopy (NIRS) can detect vascular changes in cerebral cortical tissue elicited by functional stimulation. For some 10 years, another optical signal has been reported to be accessible by NIRS. This signal has been reported to correlate to the electrophysiological response rendering NIRS an exquisite non-invasive approach to investigate neurovascular coupling in the human adult. Due to their typical latency of up to hundreds of milliseconds, these signals have been termed "fast" optical signals and have been postulated to stem from scatter changes in neuronal tissue, as a fingerprint of the electrophysiological response. Here, we utter a less optimistic view on the non-invasive detectability of these changes in the human, motivated by an upper limit signal size estimation, predicting a signal size by orders of magnitude smaller than those previously reported. Also, we discuss the influence of small stimulus correlated movement artifacts potentially mimicking a fast optical signal. Based on invasive studies, we perform an upper limit estimation for changes in intensity and mean time of flight, which can be expected assuming a scatter change in the cerebral cortex while measuring on the surface of the head of an adult subject. Since the resulting numbers are far below those previously reported, we constructed a simple system, which minimizes technical noise. The system allows us to detect rather small intensity changes (2 x 10(-3)%) when averaging over approximately 3000 stimuli. Despite this outstandingly low noise level of the system, we find a reliable change in response to a sub-motor-threshold steady state median nerve stimulation in just one single subject (8 subjects examined, 4 subjects twice). Exceeding the motor threshold leads to large stimulus related artifacts, on a similar time scale and with comparable amplitude as previously reported signals. To check for potential modality specific problems, we next performed a visual stimulation study, avoiding potential motor artifacts. For the steady state visually evoked response, no subject yielded a reliable result (11 subjects examined, 4 subjects twice). The paper discusses these findings by a review of the literature on fast optical signals and their being accessible in the adult human.

Adult↗
PubMed2004

Time-resolved multidistance near-infrared spectroscopy of the adult head: intracerebral and extracerebral absorption changes from moments of distribution of times of flight of photons.

We report on multidistance time-resolved diffuse reflectance spectroscopy of the head of a healthy adult after intravenous administration of a bolus of indocyanine green. Intracerebral and extracerebral changes in absorption are deduced from moments (integral, mean time of flight, and variance) of the distributions of times of flight of photons (DTOFs), recorded simultaneously at four different source-detector separations. We calculate the sensitivity factors converting depth-dependent changes in absorption into changes of moments of DTOFs by Monte Carlo simulations by using a layered model of the head. We validate our method by analyzing moments of DTOFs simulated for the assumed changes in absorption in different layers of the head model.

Algorithms↗
PubMed2004

Neurovascular coupling analyzed non-invasively in the human brain.

Most functional brain imaging methods detect neuronal activations indirectly through the accompanying neurovascular response. Here, we demonstrate that a novel methodological approach, the combination of DC-magnetoencephalography (DC-MEG) and near-infrared spectroscopy (NIRS), allows non-invasive assessment of the dynamics of neurovascular coupling in the human brain: detecting directly slow neuronal processes (with time constants of 30s), DC-MEG revealed, even in unaveraged recordings, sustained neuronal activations at pericentral hand cortices contralateral to repetitive finger movements; these were accompanied by the ensuing local vascular response showing similar dynamical features as quantified by simultaneously recorded NIRS. This non-invasive approach opens a new avenue for the understanding of neurovascular coupling during physiological tasks as well as in diseases involving slow neuronal depolarization shifts and alterations of blood flow, such as stroke or migraine.

Adult↗
PubMed2004

Decrease in haemoglobin oxygenation during absence seizures in adult humans.

Near-infrared spectroscopy (NIRS) is a noninvasive method that allows the assessment of activation-induced cortical oxygenation changes in humans. It has been demonstrated that an increase in oxygenated and a decrease in deoxygenated haemoglobin can be expected over an area activated by functional stimulation. Likewise, an inverse oxygenation pattern has been shown to be associated with cortical deactivation. The aim of the current study was to determine the oxygenation changes that occur during absence seizures. We performed ictal NIRS simultaneously with video-EEG telemetry in three adult patients with typical absence seizures. NIRS probes were placed over the frontal cortex below the F1/F2 leads. During all absence seizures studied, pronounced changes in cerebral Hb-oxygenation were noted and there were no changes in the interval. We observed a reproducible decrease in [oxy-Hb] and an increase in [deoxy-Hb] during absence seizures indicating a reduction of cortical activity. Oxygenation changes started several seconds after the EEG-defined absence onset and outlasted the clinically defined event by 20-30 s.

Adult↗
PubMed2004

Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact.

The detection of redox changes in cytochrome-c-oxidase ([Cyt-ox]) in response to cerebral activation by non-invasive NIRS is hampered by methodological spectroscopic issues related to the modification of the Beer-Lambert law. Also, the question whether a change in the enzyme's redox-state is elicited by functional stimulation is unresolved. In a previous study, we found physiological evidence in favour of an activation-induced increase in oxidation of the enzyme [J. Cereb. Blood Flow Metab. 19 (1999) 592], while in a second study on spectroscopic cross talk, we found that the [Cyt-ox] changes to potentially be an artefact of the spectroscopic approach [J. Biomed. Opt. 7 (2002) 51]. Here, we use two different stimuli which differentially activate areas either rich or poor in [Cyt-ox] content (blob/interblob in visual cortex V1 and pale/thin stripes in V2) to further clarify this apparent discrepancy. In a first experiment, two stimuli were presented in an alternating fashion for 20 s and all stimulation periods were separated by resting periods of 40 s. We observed similar changes in [Cyt-ox] for both stimuli. To become more sensitive to the potentially very small optical changes related to changes in [Cyt-ox], we tried to minimise global haemodynamic and metabolic effects in a second experiment by omitting the resting periods. Our hypothesis was that [Cyt-ox] changes could be fully explained by cross talk as it is predicted from our last study [J. Biomed. Opt. 7 (2002) 51]. However, in more than half of the experiments, we were not able to model the changes in Cyt-ox calculated from measured attenuation spectra as a cross talk artefact. We interpret this finding as an argument in favour of the existence of [Cyt-ox] changes in response to functional stimulation. This finding, however, does not lessen the liability of the [Cyt-ox] changes to cross talk and calls for great caution when [Cyt-ox] changes are derived from NIRS measurements based on the modified Beer-Lambert approach. Further (invasive) validation studies are required.

Adult↗
PubMed2004

Towards a standard analysis for functional near-infrared imaging.

Functional near-infrared spectroscopy (fNIRS) allows the ability to monitor brain activation by measuring changes in the concentration of oxy- and deoxy-hemoglobin. Until now no standardized approach for fNIRS data analysis has been established, although this has to be regarded as a precondition for future application. Hence, we applied the well-established general linear model to optical imaging data. Further, fNIRS data were analyzed in the frequency domain. Two visual tasks were investigated with optical imaging: a checkerboard paradigm supposed to activate the primary and secondary visual cortex, and a paradigm consisting of moving colored stimuli (rotating 'L's) additionally involving the motion area V5. Analysis with the general linear model detected the activation focus in the primary and secondary visual cortex during the first paradigm. For the second paradigm, a second laterally localized activated brain region was found, most likely representing V5. Spatially resolved spectral analysis confirmed the results by showing maxima of power spectral density and coherence in the same respective brain regions. Moreover, it demonstrated a delay of the hemodynamic response in the motion area. In summary, the present study suggests that the general linear model and spatially resolved spectral analysis can be used as standard statistical approaches for optical imaging data, particularly because they are almost independent of the assumed differential path length factors.

Adult↗
PubMed2004

Separability and cross talk: optimizing dual wavelength combinations for near-infrared spectroscopy of the adult head.

By means of noninvasive near-infrared spectroscopy (NIRS), cerebral concentration changes in oxygenated and deoxygenated hemoglobin ([oxy-Hb] and [deoxy-Hb]) can be determined. The quality of the concentration changes' assessment critically depends on the wavelength combination used. Trying to optimize this combination, two spectroscopic effects must be taken into account: cross talk and separability. Cross talk between [oxy-Hb] and [deoxy-Hb] occurs because the assumption made in the analysis-that there is a homogeneous concentration change-does not hold true for the adult human head. Separability-to be introduced in this paper-is a measure for the degree of physical noise of the measurement that will influence the noise of the concentration changes' assessment. In other words, high separability corresponds to a low noise with respect to the concentration changes assessed. Here, we present analytical expressions for both measures and provide model-based estimates of cross talk and separability for any combination of two wavelengths between 610 and 920 nm. These theoretical considerations allow for two predictions: (a) if both wavelengths used are greater than approximately 780 nm, cross talk is high and separability is low resulting in erroneous and noisy concentration data. (b) If one wavelength is chosen below 720 nm while the other is greater than 730 nm, cross talk is low and separability is high resulting in accurate concentration changes. We show the relevance of these theoretical results for noninvasive NIRS by testing the predictions on experimental data obtained in adults undergoing visual stimulation.

Adult↗
PubMed2003

Functional assessment of Broca's area using near infrared spectroscopy in humans.

We used near-infrared spectroscopy (NIRS) to compare functional hemoglobin concentration changes (delta[oxy-Hb] and delta[deoxy-Hb]) over human language and motor cortices. Eight subjects performed finger opposition, tongue movement, and covert visual object naming in an interleaved block paradigm design. NIRS revealed paradigm specific patterns of delta[oxy-Hb] and delta[deoxy-Hb] providing cortical localization of each function. During each task, significant response overlap was observed when comparing the [oxy-Hb] signals, whereas delta[deoxy-Hb] seemed more localized. Furthermore, by applying magnitude and time to significance measures to the delta[deoxy-Hb] response profile, Broca's area was easily distinguished from neighboring tongue (and hand) motor representation. Delta[oxy-Hb] did not provide this level of specificity. These findings suggest delta[deoxy-Hb] as the preferential NIRS parameter to map language cortices.

Adult↗
PubMed2003

Are VEP correlated fast optical signals detectable in the human adult by non-invasive nearinfrared spectroscopy (NIRS)?

The potential of near infrared spectroscopy (NIRS) to detect vascular changes in cerebral cortical tissue elicited by functional stimulation has been established (1). The vascular response is considered the result of neuronal activity in the investigated area and forms the basis of imaging techniques such as BOLD-contrast fMRI and PET. In the animal optical methods have been shown to detect optical changes in the illuminated tissue which exactly follow the time course of electrical potential changes, thus optical techniques can potentially assess both the 'fast' neuronal and the 'slow' vascular response. Lately a group of investigators has reported data showing that the 'fast optical signal' is detectable in the adult human in response to a visual stimulus ("optical VEP" termed EROS, i.e. event related optical signal). We failed to reproduce these results, with an almost identical instrumentation and experimental protocol. The negative result is reported in this paper. To check the expected magnitude of such changes we performed a simulation based on data reported in the animal and a human head model of optical properties. The result indicates that changes in optical properties to be expected in a non-invasive approach in the human adult are about three orders of magnitude smaller than those reported previously by the group of Gratton and co-workers (2). Also they are so small that they are below the noise level of the presently available NIRS monitors.

Adult↗
PubMed2003

Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy.

We used simultaneous electroencephalogram-functional magnetic resonance imaging (EEG-fMRI) and EEG-near infrared spectroscopy (NIRS) to investigate whether changes of the posterior EEG alpha rhythm are correlated with changes in local cerebral blood oxygenation. Cross-correlation analysis of slowly fluctuating, spontaneous rhythms in the EEG and the fMRI signal revealed an inverse relationship between alpha activity and the fMRI-blood oxygen level dependent signal in the occipital cortex. The NIRS-EEG measurements demonstrated a positive cross-correlation in occipital cortex between alpha activity and concentration changes of deoxygenated hemoglobin, which peaked at a relative shift of about 8 s. Our data suggest that alpha activity in the occipital cortex is associated with metabolic deactivation. Mapping of spontaneously synchronizing distributed neuronal networks is thus shown to be feasible.

Adult↗
PubMed2003

Beyond the visible--imaging the human brain with light.

Optical approaches to investigate cerebral function and metabolism have long been applied in invasive studies. From the neuron cultured to the exposed cortex in the human during neurosurgical procedures, high spatial resolution can be reached and several processes such as membrane potential, cell swelling, metabolism of mitochondrial chromophores, and vascular response can be monitored, depending on the respective preparation. The authors focus on an extension of optical methods to the noninvasive application in the human. Starting with the pioneering work of Jöbsis 25 years ago, near-infrared spectroscopy (NIRS) has been used to investigate functional activation of the human cerebral cortex. Recently, several groups have started to use imaging systems that allow the generation of images of a larger area of the subject's head and, thereby, the production of maps of cortical oxygenation changes. Such images have a much lower spatial resolution compared with the invasively obtained optical images. The noninvasive NIRS images, however, can be obtained in undemanding set-ups that can be easily combined with other functional methods, in particular EEG. Moreover, NIRS is applicable to bedside use. The authors briefly review some of the abundant literature on intrinsic optical signals and the NIRS imaging studies of the past few years. The weaknesses and strengths of the approach are critically discussed. The authors conclude that NIRS imaging has two major advantages: it can address issues concerning neurovascular coupling in the human adult and can extend functional imaging approaches to the investigation of the diseased brain.

Brain↗
PubMed2002

Habituation of the visually evoked potential and its vascular response: implications for neurovascular coupling in the healthy adult.

In the human, visually evoked potentials (VEP) and cerebral oxygenation changes, as measured by near-infrared spectroscopy (NIRS), are assessed to elucidate the relation between electrophysiological and vascular responses to a checkerboard stimulus reversing at 3 Hz. Habituation of either response is analysed on two time scales. Within the 1-min stimulation period we find a decrease in P100N135-component amplitude, closely coupled to a decrease in the amplitude of the oxygenation parameters (concentration changes in oxygenated and deoxygenated haemoglobin, [oxy-Hb] and [deoxy-Hb]). The N75P100-component amplitude exhibits a different behaviour along the 1-min stimulation period. An initial increase is overridden by an overall decrease, the latter not reaching statistical significance. The analysis across the 13 successive stimulation blocks separated by resting periods of equal duration yields a trend for an decrease in the VEP-components' amplitude, not reflected in the vascular response. When calculating a ratio between the amplitude of the P100N135-component and the concentration changes in the haemoglobins a "coupling index" of a 0.2 microM decrease in [deoxy-Hb] and an increase of 0.6 microM in [oxy-Hb] is found per 1 microV increase in VEP-component amplitude. The ratio is the same irrespective of its assessment from the difference stimulation/ rest or from the habituation effect, i.e., the difference between the amplitudes at the beginning and towards the end of the stimulation period. Although supporting the notion that the coupling between neuronal activation and the vascular response exhibits linear aspects, our findings cannot be taken as a proof of such a linearity across all brain regions and activation types. On the contrary, tentatively calculating a coupling index for the data assessed in the visual system, we intend to stress the necessity to assess both neuronal and vascular response to allow for a comparison between different systems and conditions in whom neurovascular coupling is expected to be altered (Miller et al, 2001; Mechelli et al, 2001).

Adult↗
PubMed2002

Noninvasive monitoring of cerebral blood flow by a dye bolus method: separation of brain from skin and skull signals.

Tracking a bolus of contrast agent traveling through the cerebral vasculature provides a measure of the blood flow velocity in the respective cerebral tissue. This principle has been the basis for the first approaches in functional magnetic resonance (MR) imaging and is of great value for investigating patients with vascular disease, especially stroke. While bolus measurements are a standard procedure in MR imaging, optical bolus tracking is as yet not established. Here we study optical absorption changes induced by a bolus of the dye indocyanine-green with near infrared spectroscopy in healthy volunteers. The aim is to assess the latency and shape of the change in absorption. Since application in the adult human critically depends on differentiation between extra- and intracerebral vascular compartments we focus on an approach for such a separation. To do this frequency-domain and multidistance measurements are analyzed by a Monte Carlo based model for photon transport in tissue. Based on measurements of both the photon's mean time of flight (phase) and the intensity, our results allow differentiation between an upper (skin and skull) and a lower layer (brain). The bolus in the deeper tissue layers has a peak of about 10 s width, while the change in absorption in the upper layers shows a much longer recovery time. This is in qualitative agreement with MR imaging results using a gadolinium bolus. This result is promising with respect to the potential of bedside monitoring of mean transit time (MTT) changes in patients with stroke or related vascular disease.

Adult↗