Original Paper Neuropsychobiology 2006;53:77–82 DOI: 10.1159/000091723
Received: November 8, 2004 Accepted after revision: October 4, 2005 Published online: February 23, 2006
Event-Related Visual versus Blocked Motor Task: Detection of Specific Cortical Activation Patterns with Functional Near-Infrared Spectroscopy M.M. Plichta M.J. Herrmann A.-C. Ehlis C.G. Baehne M.M. Richter A.J. Fallgatter Laboratory for Psychophysiology and Functional Imaging, University Hospital of Psychiatry and Psychotherapy Würzburg, Würzburg, Germany
Key Words Multi-channel functional near-infrared spectroscopy Event-related visual stimulation Motor stimulation Optical topography
Abstract The purpose of this study was to investigate the regional specificity of multi-channel functional near-infrared spectroscopy (fNIRS) in the detection of cortical activation in humans. Therefore, brain activation evoked by a visual as well as a motor task was examined using 52channel fNIRS. Analyses demonstrated an isolated activation in the occipital area during visual stimulation, whereas other regions exhibited little or no activation. Analyses of the motor task data clearly identified a differential activation pattern. The observation of an extensive cortical area by multi-channel measurement during two different tasks made it possible to examine the extent to which fNIRS measurements detect regional specific activations. We conclude that fNIRS measurements can detect regionally isolated cortical activation. Copyright © 2006 S. Karger AG, Basel
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Introduction
Functional near-infrared spectroscopy (fNIRS) is a well-established method of observing the ‘brain at work’. Based on the tight coupling of neural activity and oxygen delivery, changes in the concentration of oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin are quantified and taken as indicators for cortical activation. Therefore, near-infrared light is transmitted through the skull and cortical tissue. This easily penetrating light is absorbed mainly by two chromophores (O2Hb and HHb) and is partially reflected to the skull surface where it is detected. From the ratio of emitted/detected light the amount of chromophores is derived. By using different wavelengths of near-infrared light it is possible to calculate concentration changes of O2Hb and HHb separately. Compared with other techniques like positron emission tomography or functional magnetic resonance imaging (fMRI), fNIRS has the advantage of its straightforward application. No contrast agency application or complex technical arrangements are necessary. Additionally, the data collection is comfortable for the subjects because of less constrictive measurement circumstances (e.g. less movement restrictions, no noise disturbance). Applications of fNIRS range from 1-channel [1] to 172-channel [2] measurements. Research objectives vary from physiologically orientated questions such as visual
M.M. Plichta, Laboratory for Psychophysiology and Functional Imaging Department of Psychiatry and Psychotherapy, University Hospital Würzburg Füchsleinstrasse 15, DE–97080 Würzburg (Germany) Tel. +49 931 201 77 440, Fax +49 931 201 77 550 E-Mail
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[3], auditory [4] and motor evoked responses [5] to neuropsychologically orientated questions such as the application of the verbal fluency test [6], the continuous performance test [7], the Stroop task [8, 9] or emotional induction [10]. Considering the development of experimental designs, blocked task paradigms as used in the past are supplemented by recently accomplished eventrelated study designs [5, 9, 11–14]. Despite the variety of fNIRS applications, little is known about the regional specificity of cortical activation detection (which is different from spatial resolution of NIRS). Regional specificity can be addressed by applying two different tasks. These tasks should reliably evoke brain activity in spatially different regions (e.g. known from preceding fNIRS studies or results from other neuroimaging methods). In an early study [15], activation beneath the prefrontally located 2-channel fNIRS sensors (one channel on each side) during a language processing task was described. To ensure that this activation is taskspecific the authors also monitored the prefrontal region during a nonverbal control task (picture observation). Based on the fact that no activation was detectable during the control task, the authors concluded that their main finding of activation evoked by language processing in prefrontal regions was regional specific. However, it remains unclear if the control task actually evoked any activation since no sensors could be placed over areas which were assumed to be specific for the control task. Furthermore, it was not investigated if the assumed language-related activation is detectable at different locations. Consequently, the explanation of a regionally unspecific global activation could not be refuted. This is a common hypothesis since in many fNIRS studies the activation exceeds the border of small probe sets [e.g. 14, 16–18], or the borders are even not identifiable because single (or one per side) channel systems are used. The lack of knowledge about the regional specificity of fNIRS measurements is limiting the explanatory power of conclusions about the origins and/or the extent of cortical activation. Thus, probe sets may be placed suboptimally (i.e. leading to a failure to detect the centre of activation) or may even be too small to detect the whole extent of activation (i.e. leading to an incomplete interpretation of functionally involved cortical areas). Even when an appropriately sized probe set is perfectly placed for the detection of one centre of activation, misinterpretations can occur in case of undetected other ‘hot spots’. Independent of the localization and the extent of the used probe set, the question of false alarms in activation detection is another limiting factor in conclusions drawn from fNIRS data.
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In the present study, 52-channel fNIRS was used to detect functional activity in very well defined and established cortical areas. Firstly, visual evoked activation in the occipital region was examined using an event-related test design. Concordant with fMRI studies [e.g. 19], the aim was to demonstrate isolated activation in the well established occipital region [20]. Secondly, the sensorimotor region was examined using the same probe set without changing the optode positions. Therefore, an auditorily paced tapping task was chosen. The tapping task was performed in a blocked design to reduce the confounding effect of the auditory signal at the beginning and at the end of the motor task. Our interest was focused on the detection of spatially distinguishable activation patterns caused by the different tasks. Herein, using a largefield probe set enabled us to observe brain areas usually not monitored during the applied tasks in order to evaluate the amount of unexpected activation.
Materials and Methods Subjects Eighteen healthy volunteers (9 female and 9 male, mean age 29.5 8 6.2 years) participated in the present study. All subjects had normal or corrected to normal vision. One subject was left-handed. No subject had a history of any (neurologic) disorder potentially significant for the present study tasks. All subjects were informed about the nature of the experiment as well as the operating mode of the NIRS instrument. A brief instruction to remain relaxed and to avoid any major body movement was given. Procedure For the visual task, subjects were seated in a comfortable chair facing a 21-inch monitor in a distance of approximately 70 cm in a totally dark room. The visual stimulation was performed in an event-related paradigm by presenting an empty white screen flashing up for 1,000 ms followed by 12 s of a black screen presentation. The number of trials was set to 20. The hands were alternated in the tapping task. Subjects performed auditorily paced finger tapping (using sequentially all fingers and thumbs) of approximately 2 Hz for 10 s. After the auditory ‘stop’-signal, a 20-second resting period followed. Three blocks of left hand and three blocks of right hand tapping were performed. To prevent visual stimulation eyes remained closed during the whole tapping task. Near-Infrared Spectroscopy. Relative changes of O2Hb and HHb were measured by the ETG-4000 (Hitachi Medical Co., Japan) using a 3 ! 11 optode probe set (consisting of 16 photodetectors and 17 light emitters) resulting in a total of 52 channels (fig. 1a). Each laser diode emits light onto the subject’s scalp. The emitted light is of two different wavelengths (695 8 20 nm and 830 8 20 nm), and its frequency is modulated in wavelengths and channels to prevent crosstalk. The reflected light leaving the tissue is received by the photodetectors and transmitted into a set of lock-in amplifiers which are limited to the particular frequencies of inter-
Plichta/Herrmann/Ehlis/Baehne/Richter/ Fallgatter
Fig. 1. a Representation of the channel scheme (red squares are emitters; blue squares are detectors; numbers represent the channels). b Statistical activation maps (t values) of cerebral O2Hb concentration during event-related visual stimulation compared with the baseline condition. c, d Activation during the left and the right hand
performance, respectively. Significant channels are labeled. Note that the activation maps are approximately superimposed on a standard anatomical brain. The scales of t values are different for the visual and the motor task.
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est. Signals are then analyzed and transformed according to their wavelength and location, resulting in quantifications of the changes in the concentration of O2Hb and HHb for every NIRS channel. The unit of measurement is mmol ! mm because the exact path length is not measured by the ETG-4000. The probe set of 52-channel fNIRS was placed on the scalp with its lowest-row centre optode at position Oz according to the extended 10–20 system, expanding symmetrically to positions T7 and T8. The interoptode distance was 30 mm, which resulted in measuring approximately 30 mm beneath the scalp. Sampling rate was set to 10 Hz. Analysis of Data Visual Task. Each trial of 13-second duration was separated into baseline and activation periods. The interval of 1,000 ms preceding the visual stimulation was defined as the baseline period. The interval of 6–12 s was defined as the activation period. Typically, the hemodynamic response is inside this time window (e.g. in a study by Jasdzewski et al. [5] the peak time is around 7.5 s after visual stimulation and turns to zero after approx 15 s). Averaged values of O2Hb and HHb concentration during the baseline and activation periods were taken as the basis for statistical analyses. Data remained unfiltered due to the absence of any serious artefacts. Paired t tests were calculated to identify the activated channels. Activation was defined as a significant signal change between the baseline and the activation period1. An uncorrected alpha level of 0.05 was used. Motor Task. Each of the three blocks of 10-second right hand and left hand performance, was divided into baseline and activation periods. The interval of 10 s preceding the task period was defined as the baseline period. Task period (10 s) and the succeeding 10 s were defined as the activation period. As in the visual task, the averaged concentration of O2Hb and HHb during these periods was the basis for statistical analyses. Considering the blocked design of the tapping task, a higher statistical power was assumed. Thus, the channel-wise paired t tests were based on an alpha level of 0.01 (uncorrected). In order to compare the three different activation patterns (visual evoked, left and right hand performance) a rank order correlation matrix was computed using Spearman rho coefficients.
Results
Visual Task Significant increase in activation (p ! 0.05) could be demonstrated in 11 channels (channels 17, 18, 28, 36–39 and 46–49). As expected, the detected activation was distinctly localized in occipital regions (fig. 1b).
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A justified interpretation of t values as indicators for activation requires a constant path length factor during the baseline and activation periods. Wobst et al. [21] demonstrated that the change of the path length is negligible and fNIRS parameters mainly reflect changes in hemoglobin concentration. Thus it seems to be reasonable to interpret the order of the derived t values. However, in the present study our aim was not to evaluate or compare the degree of activation but solely investigate distinguishable activation patterns evoked by different tasks.
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Regarding HHb data, we failed to detect any specific task-related pattern of activated and nonactivated channels. Forty-nine out of the 52 channels showed a significant decrement in HHb during the activation period (p ! 0.05). The remaining 3 nonsignificant channels were solely located in the left area of the probe set (channels 32, 33 and 43). Motor Tapping Task Analyses of O2Hb changes resulting from the right hand performance demonstrated a significant (p ! 0.01) activation in channels 1, 2, 11, 12 and 16 (fig. 1d) located over the contralateral motor region (except channel 16). No ipsilateral activation was detectable. Examining the left hand performance, significant activations were found in channels 1, 10, 12, 20, 21 and 31 (fig. 1c), demonstrating both contra- and ipsilateral activation in motoric regions. Analyses of HHb failed to detect a systematic pattern of activated and of nonactivated channels (20 channels exhibited a significant decrement in HHb). Regarding the right hand performance, the analyses of HHb demonstrated 2 channels exhibiting a significant decrement (channels 1 and 21) and 3 channels which showed a significant increase in HHb (channels 32, 43 and 52). All these channels were (as expected) solely located in the lateral areas of the probe set, whereas the channels associated with a significant increase were located in the lowest two rows of the probe set. Correlation of the Three Activation Patterns We descriptively examined the correlation of the three different activation patterns (visual, left and right hand performance) to quantify their similarity and dissimilarity. Therefore, the averaged concentrations of O2Hb per channel were transformed into rank orders to prevent biased correlation coefficients due to the smaller variances obtained under the visual task. For the quantification of the similarity/dissimilarity, Spearman rho coefficients were used. Regarding the tapping tasks (left vs. right), analyses revealed a highly similar activation pattern across the channels (rho = 0.76), whereas the visual task exhibited dissimilarity to both tapping tasks (left: rho = 0.20; right: rho = 0.10). Regarding HHb, similarity analysis was not performed due to the less specific findings. Note that the reported results do not change substantially when the left-handed subject is removed from the analyses.
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Discussion
The aim of the present study was to investigate the regional specificity of multi-channel fNIRS in the detection of human cortical activation caused by different tasks. Therefore, we used 52-channel fNIRS measurement. The activation pattern obtained by a visual task was contrasted descriptively with a block-design motor task. In agreement with former fMRI [22, 23] and fNIRS studies [5, 16], our results show that major activation is identifiable in the expected occipital and sensorimotor brain regions. Little to no overlap in the activation patterns was identifiable by the post-hoc procedure and the calculated similarity/dissimilarity indices. Interestingly, our results show a more pronounced activation (i.e. a higher number of channels associated with a significant signal change) during the nondominant than during the dominant hand performance (fig. 1c, d). It has been proposed that the left premotor region is the controlling site for motor tasks when dominance is in the left hemisphere (which was the case in the majority of our subjects) [22]. Since the left hand performance represents a more demanding task, the more pronounced ipsilateral activation could reasonably be explained by the need of more control. Because of the application of a 52-channel large-field observation, it was possible to examine activity in cortical regions usually not monitored. Based on this, it was possible to detect unexpected activity mainly during the right hand performance in channel 16 localized near the interhemispheric fissure (with a t value of 3.15 comparable to the expected amount of O2Hb concentration change in channel 2, which is t = 3.36). Since fNIRS measurement is limited to the cortical surface, the possibility of detecting an interhemispheric interaction between functionally involved cortical areas (corpus callosum) seems highly unlikely. Furthermore, there are no major arteries beneath the position of channel 16 which could explain the detected activation, e.g. by oxygen delivery towards the involved sensorimotor areas. Therefore, the possibility of a false alarm should be taken as most likely, although the sample size and the obtained t value corresponding to channel 16 argue against this possibility. As a consequence, it seems advisable not to interpret isolated significant channels which are not framed by or adjacent to other significant channels. Regarding our conclusions about the similarity/dissimilarity of the different task-related activation patterns, one could argue that the small amount of overlap in the patterns of activation was facilitated by adjusting the alpha level to the value of 0.01 in the motor task analyses.
Detection of Specific Cortical Activation Patterns with fNIRS
However, this adjustment seems reasonable and necessary due to the accumulating nature of concentration changes obtained in the block design motor task. The more lax alpha criterion in the analyses of visual stimulation was chosen to achieve the necessary sensitivity of the fNIRS measurement. Another reason for the more lax alpha criterion is that the chosen ITI of 12 s leads to an overlap of the hemodynamic responses of the trials. As a result, a relatively high level of hemoglobin concentration exists during the baseline period as we defined it. Thus the applied post-hoc tests of the visual task have a lower power compared to those of the motor task. Our analyses of HHb failed to detect regionally specific activation patterns during the visual task and during the left hand performance. These findings stand in contrast to the position that HHb is associated with a higher signal-to-noise ratio [9, 24]. Even a stricter alpha level (0.001) does not emphasize the expected activation in the assumed areas and/or reduce the activation detection in locally unexpected areas of the probe set. This could be due to the application of a novel wavelength for measuring HHb (695 8 20 nm). Indeed, it remains unclear why this ‘hypersensitivity’ is not detected during the right hand performance. The demonstrated regional specificity of multi-channel fNIRS in the detection of cortical activation in humans contributes to the credibility and the adequacy of interpretations drawn from fNIRS measurement. To ensure further quality factors, the reliability of fNIRS measurements (in physiological and psychological tasks) should be examined next. Already existing results obtained from fNIRS will largely benefit from these methodological studies and the role of fNIRS would be underpinned as a remarkable and accurate tool particularly for cognitive research.
Acknowledgments The authors would like to thank Hitachi Medical Corporation for the ETG-4000 equipment and skilled technical support, and Inge Gröbner, Melanie Greutner and Ireen Schaffrath for their proficient technical assistance.
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