Hellmuth Obrig

Publications of Hellmuth Obrig

• Somatosensory activation of two fingers can be discriminated with ultrahigh-density diffuse optical tomography.

  Authors: Christina Habermehl, Susanne Holtze, Jens Steinbrink, Stefan P Koch, Hellmuth Obrig, Jan Mehnert, Christoph H Schmitz

  NeuroImage. 12/2011; 59(4):3201-11.

  Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving aTopographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a spatial resolution in the centimeter range. This resolution is poor compared to other functional imaging tools. However, recently it was shown that diffuse optical tomography (DOT) as an extension of NIRS based on high-density (HD) probe arrays and supplemented by an advanced image reconstruction procedure allows describing activation patterns with a spatial resolution in the millimeter range. Building on these findings, we hypothesize that HD-DOT may render very focal activations accessible which would be missed by the traditionally used sparse arrays. We examined activation patterns in the primary somatosensory cortex, since its somatotopic organization is very fine-grained. We performed a vibrotactile stimulation study of the first and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT imaging system for achieving a higher resolution than conventional topographic NIRS. To compare the results to a well-established high-resolution imaging technique, the same paradigm was investigated in the same subjects by means of functional magnetic resonance imaging (fMRI). In this work, we tested the advantage of ultrahigh-density probe arrays and show that highly focal activations would be missed by classical next-nearest neighbor NIRS approach, but also by DOT, when using a sparse probe array. Distinct activation patterns for both fingers correlated well with the expected neuroanatomy in five of eight subjects. Additionally we show that activation for different fingers is projected to different tissue depths in the DOT image. Comparison to the fMRI data yielded similar activation foci in seven out of ten finger representations in these five subjects when comparing the lateral localization of DOT and fMRI results.

• Non-invasive optical imaging of stroke.

  Authors: Hellmuth Obrig, Jens Steinbrink

  Philosophical transactions. Series A, Mathematical, physical, and engineering sciences. 11/2011; 369(1955):4470-94.

  The acute onset of a neurological deficit is the key clinical feature of stroke. In most cases, however, pathophysiological changes in the cerebral vasculature precede the event, often by many years.The acute onset of a neurological deficit is the key clinical feature of stroke. In most cases, however, pathophysiological changes in the cerebral vasculature precede the event, often by many years. Persisting neurological deficits may also require long-term rehabilitation. Hence, stroke may be considered a chronic disease, and diagnostic and therapeutic efforts must include identification of specific risk factors, and the monitoring of and interventions in the acute and subacute stages, and should aim at a pathophysiologically based approach to optimize the rehabilitative effort. Non-invasive optical techniques have been experimentally used in all three stages of the disease and may complement the established diagnostic and monitoring tools. Here, we provide an overview of studies using the methodology in the context of stroke, and we sketch perspectives of how they may be integrated into the assessment of the highly dynamic pathophysiological processes during the acute and subacute stages of the disease and also during rehabilitation and (secondary) prevention of stroke.

• Dreamed movement elicits activation in the sensorimotor cortex.

  Authors: Martin Dresler, Stefan P Koch, Renate Wehrle, Victor I Spoormaker, Florian Holsboer, Axel Steiger, Philipp G Sämann, Hellmuth Obrig, Michael Czisch

  Current biology : CB. 11/2011; 21(21):1833-7.

  Since the discovery of the close association between rapid eye movement (REM) sleep and dreaming, much effort has been devoted to link physiological signatures of REM sleep to the contents ofSince the discovery of the close association between rapid eye movement (REM) sleep and dreaming, much effort has been devoted to link physiological signatures of REM sleep to the contents of associated dreams [1-4]. Due to the impossibility of experimentally controlling spontaneous dream activity, however, a direct demonstration of dream contents by neuroimaging methods is lacking. By combining brain imaging with polysomnography and exploiting the state of "lucid dreaming," we show here that a predefined motor task performed during dreaming elicits neuronal activation in the sensorimotor cortex. In lucid dreams, the subject is aware of the dreaming state and capable of performing predefined actions while all standard polysomnographic criteria of REM sleep are fulfilled [5, 6]. Using eye signals as temporal markers, neural activity measured by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) was related to dreamed hand movements during lucid REM sleep. Though preliminary, we provide first evidence that specific contents of REM-associated dreaming can be visualized by neuroimaging.

• Implicit processing of phonotactic cues: evidence from electrophysiological and vascular responses.

  Authors: Sonja Rossi, Ina B Jürgenson, Adriana Hanulíková, Silke Telkemeyer, Isabell Wartenburger, Hellmuth Obrig

  Journal of cognitive neuroscience. 07/2011; 23(7):1752-64.

  Spoken word recognition is achieved via competition between activated lexical candidates that match the incoming speech input. The competition is modulated by prelexical cues that are important forSpoken word recognition is achieved via competition between activated lexical candidates that match the incoming speech input. The competition is modulated by prelexical cues that are important for segmenting the auditory speech stream into linguistic units. One such prelexical cue that listeners rely on in spoken word recognition is phonotactics. Phonotactics defines possible combinations of phonemes within syllables or words in a given language. The present study aimed at investigating both temporal and topographical aspects of the neuronal correlates of phonotactic processing by simultaneously applying ERPs and functional near-infrared spectroscopy (fNIRS). Pseudowords, either phonotactically legal or illegal with respect to the participants' native language, were acoustically presented to passively listening adult native German speakers. ERPs showed a larger N400 effect for phonotactically legal compared to illegal pseudowords, suggesting stronger lexical activation mechanisms in phonotactically legal material. fNIRS revealed a left hemispheric network including fronto-temporal regions with greater response to phonotactically legal pseudowords than to illegal pseudowords. This confirms earlier hypotheses on a left hemispheric dominance of phonotactic processing most likely due to the fact that phonotactics is related to phonological processing and represents a segmental feature of language comprehension. These segmental linguistic properties of a stimulus are predominantly processed in the left hemisphere. Thus, our study provides first insights into temporal and topographical characteristics of phonotactic processing mechanisms in a passive listening task. Differential brain responses between known and unknown phonotactic rules thus supply evidence for an implicit use of phonotactic cues to guide lexical activation mechanisms.

• Shedding light on words and sentences: Near-infrared spectroscopy in language research.

  Authors: Sonja Rossi, Silke Telkemeyer, Isabell Wartenburger, Hellmuth Obrig

  Brain and language. 05/2011;

  Investigating the neuronal network underlying language processing may contribute to a better understanding of how the brain masters this complex cognitive function with surprising ease and howInvestigating the neuronal network underlying language processing may contribute to a better understanding of how the brain masters this complex cognitive function with surprising ease and how language is acquired at a fast pace in infancy. Modern neuroimaging methods permit to visualize the evolvement and the function of the language network. The present paper focuses on a specific methodology, functional near-infrared spectroscopy (fNIRS), providing an overview over studies on auditory language processing and acquisition. The methodology detects oxygenation changes elicited by functional activation of the cerebral cortex. The main advantages for research on auditory language processing and its development during infancy are an undemanding application, the lack of instrumental noise, and its potential to simultaneously register electrophysiological responses. Also it constitutes an innovative approach for studying developmental issues in infants and children. The review will focus on studies on word and sentence processing including research in infants and adults.

• Focal retrograde amnesia: voxel-based morphometry findings in a case without MRI lesions.

  Authors: Bernhard Sehm, Stefan Frisch, Angelika Thöne-Otto, Annette Horstmann, Arno Villringer, Hellmuth Obrig

  PloS one. 01/2011; 6(10):e26538.

  Focal retrograde amnesia (FRA) is a rare neurocognitive disorder presenting with an isolated loss of retrograde memory. In the absence of detectable brain lesions, a differentiation of FRA fromFocal retrograde amnesia (FRA) is a rare neurocognitive disorder presenting with an isolated loss of retrograde memory. In the absence of detectable brain lesions, a differentiation of FRA from psychogenic causes is difficult. Here we report a case study of persisting FRA after an epileptic seizure. A thorough neuropsychological assessment confirmed severe retrograde memory deficits while anterograde memory abilities were completely normal. Neurological and psychiatric examination were unremarkable and high-resolution MRI showed no neuroradiologically apparent lesion. However, voxel-based morphometry (VBM)-comparing the MRI to an education-, age-and sex-matched control group (n = 20) disclosed distinct gray matter decreases in left temporopolar cortex and a region between right posterior parahippocampal and lingual cortex. Although the results of VBM-based comparisons between a single case and a healthy control group are generally susceptible to differences unrelated to the specific symptoms of the case, we believe that our data suggest a causal role of the cortical areas detected since the retrograde memory deficit is the preeminent neuropsychological difference between patient and controls. This was paralleled by grey matter differences in central nodes of the retrograde memory network. We therefore suggest that these subtle alterations represent structural correlates of the focal retrograde amnesia in our patient. Beyond the implications for the diagnosis and etiology of FRA, our results advocate the use of VBM in conditions that do not show abnormalities in clinical radiological assessment, but show distinct neuropsychological deficits.

• Acoustic processing of temporally modulated sounds in infants: evidence from a combined near-infrared spectroscopy and EEG study.

  Authors: Silke Telkemeyer, Sonja Rossi, Till Nierhaus, Jens Steinbrink, Hellmuth Obrig, Isabell Wartenburger

  Frontiers in psychology. 01/2011; 1:62.

  Speech perception requires rapid extraction of the linguistic content from the acoustic signal. The ability to efficiently process rapid changes in auditory information is important for decodingSpeech perception requires rapid extraction of the linguistic content from the acoustic signal. The ability to efficiently process rapid changes in auditory information is important for decoding speech and thereby crucial during language acquisition. Investigating functional networks of speech perception in infancy might elucidate neuronal ensembles supporting perceptual abilities that gate language acquisition. Interhemispheric specializations for language have been demonstrated in infants. How these asymmetries are shaped by basic temporal acoustic properties is under debate. We recently provided evidence that newborns process non-linguistic sounds sharing temporal features with language in a differential and lateralized fashion. The present study used the same material while measuring brain responses of 6 and 3 month old infants using simultaneous recordings of electroencephalography (EEG) and near-infrared spectroscopy (NIRS). NIRS reveals that the lateralization observed in newborns remains constant over the first months of life. While fast acoustic modulations elicit bilateral neuronal activations, slow modulations lead to right-lateralized responses. Additionally, auditory-evoked potentials and oscillatory EEG responses show differential responses for fast and slow modulations indicating a sensitivity for temporal acoustic variations. Oscillatory responses reveal an effect of development, that is, 6 but not 3 month old infants show stronger theta-band desynchronization for slowly modulated sounds. Whether this developmental effect is due to increasing fine-grained perception for spectrotemporal sounds in general remains speculative. Our findings support the notion that a more general specialization for acoustic properties can be considered the basis for lateralization of speech perception. The results show that concurrent assessment of vascular based imaging and electrophysiological responses have great potential in the research on language acquisition.

• Time-resolved near-infrared spectroscopy and imaging of the adult human brain.

  Authors: Heidrun Wabnitz, Michael Moeller, Adam Liebert, Hellmuth Obrig, Jens Steinbrink, Rainer Macdonald

  Advances in experimental medicine and biology. 01/2010; 662:143-8.

  Near-infrared spectroscopy (NIRS) of the human brain is aiming at the non-invasive determination of concentration changes of oxy- and deoxyhemoglobin in the cortex. However, it usually relies on theNear-infrared spectroscopy (NIRS) of the human brain is aiming at the non-invasive determination of concentration changes of oxy- and deoxyhemoglobin in the cortex. However, it usually relies on the assumption of spatially homogeneous absorption changes. To overcome this limitation we performed instrumental and methodological developments of time-resolved NIRS with the aim to achieve depth resolution. We present our recently developed time-domain near-infrared brain imager based on picosecond diode lasers and time-correlated single photon counting (TCSPC) which can be used at the bedside. To achieve depth localization of absorption changes we analysed statistical moments (integral, mean time of flight and variance) of measured time-of-flight distributions of diffusely reflected photons. In particular, variance has a selective sensitivity to deep absorptions changes and provides a suitable representation of cerebral signals. The separation of cerebral and extracerebral changes of hemoglobin concentrations is demonstrated for a motor stimulation experiment.

• From acoustic segmentation to language processing: evidence from optical imaging.

  Authors: Hellmuth Obrig, Sonja Rossi, Silke Telkemeyer, Isabell Wartenburger

  Frontiers in neuroenergetics. 01/2010; 2.

  During language acquisition in infancy and when learning a foreign language, the segmentation of the auditory stream into words and phrases is a complex process. Intuitively, learners use "anchors"During language acquisition in infancy and when learning a foreign language, the segmentation of the auditory stream into words and phrases is a complex process. Intuitively, learners use "anchors" to segment the acoustic speech stream into meaningful units like words and phrases. Regularities on a segmental (e.g., phonological) or suprasegmental (e.g., prosodic) level can provide such anchors. Regarding the neuronal processing of these two kinds of linguistic cues a left-hemispheric dominance for segmental and a right-hemispheric bias for suprasegmental information has been reported in adults. Though lateralization is common in a number of higher cognitive functions, its prominence in language may also be a key to understanding the rapid emergence of the language network in infants and the ease at which we master our language in adulthood. One question here is whether the hemispheric lateralization is driven by linguistic input per se or whether non-linguistic, especially acoustic factors, "guide" the lateralization process. Methodologically, functional magnetic resonance imaging provides unsurpassed anatomical detail for such an enquiry. However, instrumental noise, experimental constraints and interference with EEG assessment limit its applicability, pointedly in infants and also when investigating the link between auditory and linguistic processing. Optical methods have the potential to fill this gap. Here we review a number of recent studies using optical imaging to investigate hemispheric differences during segmentation and basic auditory feature analysis in language development.

• High-resolution optical functional mapping of the human somatosensory cortex.

  Authors: Stefan P Koch, Christina Habermehl, Jan Mehnert, Christoph H Schmitz, Susanne Holtze, Arno Villringer, Jens Steinbrink, Hellmuth Obrig

  Frontiers in neuroenergetics. 01/2010; 2:12.

  Non-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanningNon-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanning environment. Beyond physiological and psychological research, bedside monitoring and neurorehabilitation may be relevant clinical applications that are yet little explored. A major obstacle to advocate the tool in clinical research is insufficient spatial resolution. Based on a multi-distance high-density optical imaging setup, we here demonstrate a dramatic increase in sensitivity of the method. We show that optical imaging allows for the differentiation between activations of single finger representations in the primary somatosensory cortex (SI). Methodologically our findings confirm results in a pioneering study by Zeff et al. (2007) and extend them to the homuncular organization of SI. After performing a motor task, eight subjects underwent vibrotactile stimulation of the little finger and the thumb. We used a high-density diffuse-optical sensing array in conjunction with optical tomographic reconstruction. Optical imaging disclosed three discrete activation foci one for motor and two discrete foci for vibrotactile stimulation of the first and fifth finger, respectively. The results were co-registered to the individual anatomical brain anatomy (MRI) which confirmed the localization in the expected cortical gyri in four subjects. This advance in spatial resolution opens new perspectives to apply optical imaging in the research on plasticity notably in patients undergoing neurorehabilitation.

• Sensitivity of newborn auditory cortex to the temporal structure of sounds.

  Authors: Silke Telkemeyer, Sonja Rossi, Stefan P Koch, Till Nierhaus, Jens Steinbrink, David Poeppel, Hellmuth Obrig, Isabell Wartenburger

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 11/2009; 29(47):14726-33.

  Understanding the rapidly developing building blocks of speech perception in infancy requires a close look at the auditory prerequisites for speech sound processing. Pioneering studies haveUnderstanding the rapidly developing building blocks of speech perception in infancy requires a close look at the auditory prerequisites for speech sound processing. Pioneering studies have demonstrated that hemispheric specializations for language processing are already present in early infancy. However, whether these computational asymmetries can be considered a function of linguistic attributes or a consequence of basic temporal signal properties is under debate. Several studies in adults link hemispheric specialization for certain aspects of speech perception to an asymmetry in cortical tuning and reveal that the auditory cortices are differentially sensitive to spectrotemporal features of speech. Applying concurrent electrophysiological (EEG) and hemodynamic (near-infrared spectroscopy) recording to newborn infants listening to temporally structured nonspeech signals, we provide evidence that newborns process nonlinguistic acoustic stimuli that share critical temporal features with language in a differential manner. The newborn brain preferentially processes temporal modulations especially relevant for phoneme perception. In line with multi-time-resolution conceptions, modulations on the time scale of phonemes elicit strong bilateral cortical responses. Our data furthermore suggest that responses to slow acoustic modulations are lateralized to the right hemisphere. That is, the newborn auditory cortex is sensitive to the temporal structure of the auditory input and shows an emerging tendency for functional asymmetry. Hence, our findings support the hypothesis that development of speech perception is linked to basic capacities in auditory processing. From birth, the brain is tuned to critical temporal properties of linguistic signals to facilitate one of the major needs of humans: to communicate.

• Stimulus-induced and state-dependent sustained gamma activity is tightly coupled to the hemodynamic response in humans.

  Authors: Stefan P Koch, Peter Werner, Jens Steinbrink, Pascal Fries, Hellmuth Obrig

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 11/2009; 29(44):13962-70.

  A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention,A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus-response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35-70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging.

• Individual alpha-frequency correlates with amplitude of visual evoked potential and hemodynamic response.

  Authors: Stefan P Koch, Sophie Koendgen, Riad Bourayou, Jens Steinbrink, Hellmuth Obrig

  NeuroImage. 07/2008; 41(2):233-42.

  In a simultaneous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) study, the predictive value of the individual alpha-frequency at rest (IAF) for the amplitude of neuronal andIn a simultaneous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) study, the predictive value of the individual alpha-frequency at rest (IAF) for the amplitude of neuronal and vascular responses to visual stimulation was investigated. Across subjects, we find (i) an inverse relationship between IAF and the amplitude of the alpha-rhythm at rest. The IAF also predicts (ii) the amplitude of the visual evoked potential (VEP), as well as (iii) the amplitude of the alpha-rhythm during stimulation. Most importantly, (iv) IAF correlates with the oxygenation response to visual stimulation: A high IAF predicts a low alpha-amplitude at rest, a small VEP amplitude and a small oxygenation response. Conversely, a low IAF predicts high alpha-amplitude and larger electrophysiological and vascular responses to stimulation. Based on these findings, we assume that the relationship between IAF and neuronal and vascular response stems from the size of the network recruited for visual processing. The relation between IAF, alpha-amplitude, evoked potential and vascular response is discussed in the framework of a simple heuristic model. The results may partly explain the large intersubject variability observed in recently published concurrent EEG-fMRI studies.

• Differential activation of frontal and parietal regions during visual word recognition: an optical topography study.

  Authors: Markus J Hofmann, Martin J Herrmann, Ippeita Dan, Hellmuth Obrig, Markus Conrad, Lars Kuchinke, Arthur M Jacobs, Andreas J Fallgatter

  NeuroImage. 05/2008; 40(3):1340-9.

  The present study examined cortical oxygenation changes during lexical decision on words and pseudowords using functional Near-Infrared Spectroscopy (fNIRS). Focal hyperoxygenation as an indicator ofThe present study examined cortical oxygenation changes during lexical decision on words and pseudowords using functional Near-Infrared Spectroscopy (fNIRS). Focal hyperoxygenation as an indicator of functional activation was compared over three target areas over the left hemisphere. A 52-channel Hitachi ETG-4000 was used covering the superior frontal gyrus (SFG), the left inferior parietal gyrus (IPG) and the left inferior frontal gyrus (IFG). To allow for anatomical inference a recently developed probabilistic mapping method was used to determine the most likely anatomic locations of the changes in cortical activation [Tsuzuki, D., Jurcak, V., Singh, A.K., Okamoto, M., Watanabe, E., Dan, I., 2007. Virtual spatial registration of stand-alone fNIRS data to MNI space. NeuroImage 43 (4), 1506-1518. Subjects made lexical decisions on 50 low and 50 high frequency words and 100 pseudowords. With respect to the lexicality effect, words elicited a larger focal hyperoxygenation in comparison to pseudowords in two regions identified as the SFG and left IPG. The SFG activation difference was interpreted to reflect decision-related mechanisms according to the Multiple Read-Out Model [Grainger, J., Jacobs, A.M., 1996. Orthographic processing in visual word recognition: A multiple read-out model. Psychological Review 103, 518-565]. The greater oxygenation response to words in the left IPG suggests that this region connects orthographic, phonological and semantic representations. A decrease of deoxygenated hemoglobin was observed to low frequency in comparison to high frequency words in a region identified as IFG. This region's sensitivity to word frequency suggests its involvement in grapheme-phoneme conversion, or its role during the selection of pre-activated semantic candidates.

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

  Authors: Isabell Wartenburger, Jens Steinbrink, Silke Telkemeyer, Manuela Friedrich, Angela D. Friederici, Hellmuth Obrig

  NeuroImage. 02/2007; 34(1):416-25.

  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 correlatesBeyond 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.

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

  Authors: Jens Steinbrink, Thomas Fischer, Hermann Kuppe, Roland Hetzer, Kamil Uludag, Hellmuth Obrig, Wolfgang M Kuebler

  The Journal of thoracic and cardiovascular surgery. 12/2006; 132(5):1172-8.

  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 surgicalOBJECTIVE: 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.

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

  Authors: Stefan P Koch, Jens Steinbrink, Arno Villringer, Hellmuth Obrig

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 06/2006; 26(18):4940-8.

  We performed an electroencephalography and optical topography study simultaneously exploring electrophysiological and vascular response magnitude as a function of stimulus frequency. To elicit aWe 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.

• Illuminating the BOLD signal: combined fMRI-fNIRS studies.

  Authors: Jens Steinbrink, Arno Villringer, Florian Kempf, Daniel Haux, Stefanie Boden, Hellmuth Obrig

  Magnetic resonance imaging. 06/2006; 24(4):495-505.

  Functional magnetic resonance imaging (fMRI) is currently combined with electrophysiological methods to identify the relationship between neuronal activity and the blood oxygenation level-dependentFunctional 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.

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

  Authors: Jens Steinbrink, Florian C D Kempf, Arno Villringer, Hellmuth Obrig

  NeuroImage. 08/2005; 26(4):996-1008.

  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 beNear 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.

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

  Authors: Kâmil Uludağ, Jens Steinbrink, Arno Villringer, Hellmuth Obrig

  NeuroImage. 07/2004; 22(2):583-9.

  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 theBy 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.