Ilias Tachtsidis

The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy.

A major methodological challenge of functional near-infrared spectroscopy (fNIRS) is its high sensitivity to haemodynamic fluctuations in the scalp. Superficial fluctuations contribute on the one hand to the physiological noise of fNIRS, impairing the signal-to-noise ratio, and may on the other hand be erroneously attributed to cerebral changes, leading to false positives in fNIRS experiments. Here we explore the localisation, time course and physiological origin of task-evoked superficial signals in fNIRS and present a method to separate them from cortical signals. We used complementary fNIRS, fMRI, MR-angiography and peripheral physiological measurements (blood pressure, heart rate, skin conductance and skin blood flow) to study activation in the frontal lobe during a continuous performance task. The General Linear Model (GLM) was applied to analyse the fNIRS data, which included an additional predictor to account for systemic changes in the skin. We found that skin blood volume strongly depends on the cognitive state and that sources of task-evoked systemic signals in fNIRS are co-localized with veins draining the scalp. Task-evoked superficial artefacts were mainly observed in concentration changes of oxygenated haemoglobin and could be effectively separated from cerebral signals by GLM analysis. Based on temporal correlation of fNIRS and fMRI signals with peripheral physiological measurements we conclude that the physiological origin of the systemic artefact is a task-evoked sympathetic arterial vasoconstriction followed by a decrease in venous volume. Since changes in sympathetic outflow accompany almost any cognitive and emotional process, we expect scalp vessel artefacts to be present in a wide range of fNIRS settings used in neurocognitive research. Therefore a careful separation of fNIRS signals originating from activated brain and from scalp is a necessary precondition for unbiased fNIRS brain activation maps.

Long-Term Enhancement of Brain Function and Cognition Using Cognitive Training and Brain Stimulation

Summary Noninvasive brain stimulation has shown considerable promise for enhancing cognitive functions by the long-term manipulation of neuroplasticity [1–3]. However, the observation of such improvements has been focused at the behavioral level, and enhancements largely restricted to the performance of basic tasks. Here, we investigate whether transcranial random noise stimulation (TRNS) can improve learning and subsequent performance on complex arithmetic tasks. TRNS of the bilateral dorsolateral prefrontal cortex (DLPFC), a key area in arithmetic [4, 5], was uniquely coupled with near-infrared spectroscopy (NIRS) to measure online hemodynamic responses within the prefrontal cortex. Five consecutive days of TRNS-accompanied cognitive training enhanced the speed of both calculation- and memory-recall-based arithmetic learning. These behavioral improvements were associated with defined hemodynamic responses consistent with more efficient neurovascular coupling within the left DLPFC. Testing 6 months after training revealed long-lasting behavioral and physiological modifications in the stimulated group relative to sham controls for trained and nontrained calculation material. These results demonstrate that, depending on the learning regime, TRNS can induce long-term enhancement of cognitive and brain functions. Such findings have significant implications for basic and translational neuroscience, highlighting TRNS as a viable approach to enhancing learning and high-level cognition by the long-term modulation of neuroplasticity.

Synchronization between arterial blood pressure and cerebral oxyhaemoglobin concentration investigated by wavelet cross-correlation

Wavelet cross-correlation (WCC) is used to analyse the relationship between low-frequency oscillations in near-infrared spectroscopy (NIRS) measured cerebral oxyhaemoglobin (O(2)Hb) and mean arterial blood pressure (MAP) in patients suffering from autonomic failure and age-matched controls. Statistically significant differences are found in the wavelet scale of maximum cross-correlation upon posture change in patients, but not in controls. We propose that WCC analysis of the relationship between O(2)Hb and MAP provides a useful method of investigating the dynamics of cerebral autoregulation using the spontaneous low-frequency oscillations that are typically observed in both variables without having to make the assumption of stationarity of the time series. It is suggested that for a short-duration clinical test previous transfer-function-based approaches to analyse this relationship may suffer due to the inherent nonstationarity of low-frequency oscillations that are observed in the resting brain.

Increase in cerebral aerobic metabolism by normobaric hyperoxia after traumatic brain injury.

OBJECT Traumatic brain injury (TBI) is associated with depressed aerobic metabolism and mitochondrial dysfunction. Normobaric hyperoxia (NBH) has been suggested as a treatment for TBI, but studies in humans have produced equivocal results. In this study the authors used brain tissue O(2) tension measurement, cerebral microdialysis, and near-infrared spectroscopy to study the effects of NBH after TBI. They investigated the effects on cellular and mitochondrial redox states measured by the brain tissue lactate/pyruvate ratio (LPR) and the change in oxidized cytochrome c oxidase (CCO) concentration, respectively. METHODS The authors studied 8 adults with TBI within the first 48 hours postinjury. Inspired oxygen percentage at normobaric pressure was increased from baseline to 60% for 60 minutes and then to 100% for 60 minutes before being returned to baseline for 30 minutes. RESULTS The results are presented as the median with the interquartile range in parentheses. During the 100% inspired oxygen percentage phase, brain tissue O2 tension increased by 7.2 kPa (range 4.5-9.6 kPa) (p < 0.0001), microdialysate lactate concentration decreased by 0.26 mmol/L (range 0.0-0.45 mmol/L) (p = 0.01), microdialysate LPR decreased by 1.6 (range 1.0-2.3) (p = 0.02), and change in oxidized CCO concentration increased by 0.21 mumol/L (0.13-0.38 micromol/L) (p = 0.0003). There were no significant changes in intracranial pressure or arterial or microdialysate glucose concentration. The change in oxidized CCO concentration correlated with changes in brain tissue O(2) tension (r(s)= 0.57, p = 0.005) and in LPR (r(s)= -0.53, p = 0.006). CONCLUSIONS The authors have demonstrated oxidation in cerebral cellular and mitochondrial redox states during NBH in adults with TBI. These findings are consistent with increased aerobic metabolism and suggest that NBH has the potential to improve outcome after TBI. Further studies are warranted.

Investigation of cerebral haemodynamics by near-infrared spectroscopy in young healthy volunteers reveals posture-dependent spontaneous oscillations

Autonomic reflexes enable the cardiovascular system to respond to gravitational displacement of blood during changes in posture. Spontaneous oscillations present in the cerebral and systemic circulation of healthy subjects have demonstrated a regulatory role. This study assessed the dynamic responses of the cerebral and systemic circulation upon standing up and the posture dependence of spontaneous oscillations. In ten young healthy volunteers, blood pressure and cerebral haemodynamics were continuously monitored non-invasively using the Portapres and near-infrared spectroscopy (NIRS), respectively. Oscillatory changes in the cerebral NIRS signals and the diastolic blood pressure (DBP) signal have been identified by the fast Fourier analysis. Blood pressure increased during standing and returned to basal level when volunteers sat on a chair. The mean value of cerebral tissue oxygen index (TOI) as measured by NIRS did not demonstrate any significant changes. Oscillatory changes in DBP, oxyhaemoglobin concentration [O2Hb] and TOI showed a significant increase when subjects were standing. Investigation of the low frequency component (approximately 0.1 Hz) of these fluctuations revealed posture dependence associated with activation of autonomic reflexes. Systemic and cerebral changes appeared to preserve adequate blood flow and cerebral perfusion during standing in healthy volunteers. Oscillatory changes in [O2Hb] and TOI, which may be related to the degree of cerebral sympathetic stimulation, are posture dependent in healthy subjects.

False positives and false negatives in functional near-infrared spectroscopy: issues, challenges, and the way forward

Abstract. We highlight a significant problem that needs to be considered and addressed when performing functional near-infrared spectroscopy (fNIRS) studies, namely the possibility of inadvertently measuring fNIRS hemodynamic responses that are not due to neurovascular coupling. These can be misinterpreted as brain activity, i.e., “false positives” (errors caused by wrongly assigning a detected hemodynamic response to functional brain activity), or mask brain activity, i.e., “false negatives” (errors caused by wrongly assigning a not observed hemodynamic response in the presence of functional brain activity). Here, we summarize the possible physiological origins of these issues and suggest ways to avoid and remove them.

FALSE POSITIVES IN FUNCTIONAL NEAR-INFRARED TOPOGRAPHY

Functional cranial near-infrared spectroscopy (NIRS) has been widely used to investigate the haemodynamic changes which occur in response to functional activation. The technique exploits the different absorption spectra of oxy- and deoxy-haemoglobin ([HbO2] [HHb]) in the near-infrared region to measure the changes in oxygenation and haemodynamics in the cortical tissue. The aim of this study was to use an optical topography system to produce topographic maps of the haemodynamic response of both frontal cortex (FC) and motor cortex (MC) during anagram solving while simultaneously monitoring the systemic physiology (mean blood pressure, heart rate, scalp flux). A total of 22 young healthy adults were studied. The activation paradigm comprised of 4-, 6- and 8- letter anagrams. 12 channels of the optical topography system were positioned over the FC and 12 channels over the MC. During the task 12 subjects demonstrated a significant change in at least one systemic variable (p < or = 0.05). Statistical analysis of task-related changes in [HbO2] and [HHb], based on a Students t-test was insufficient to distinguish between cortical haemodynamic activation and systemic interference. This lead to false positive haemodynamic maps of activation. It is therefore necessary to use statistical testing that incorporates the systemic changes that occur during brain activation.

Near-infrared spectroscopic quantification of changes in the concentration of oxidized cytochrome c oxidase in the healthy human brain during hypoxemia

The near-IR cytochrome c oxidase (CCO) signal has potential as a clinical marker of changes in mitochondrial oxygen utilization. We examine the CCO signal response to reduced oxygen delivery in the healthy human brain. We induced a reduction in arterial oxygen saturation from baseline levels to 80% in eight healthy adult humans, while minimizing changes in end tidal carbon dioxide tension. We measured changes in the cerebral concentrations of oxidized CCO (Delta[oxCCO]), oxyhemoglobin (Delta[HbO(2)]), and deoxyhemoglobin (Delta[HHb]) using broadband near-IR spectroscopy (NIRS), and estimated changes in cerebral oxygen delivery (ecDO(2)) using pulse oximetry and transcranial Doppler ultrasonography. Results are presented as median (interquartile range). At the nadir of hypoxemia ecDO(2) decreased by 9.2 (5.4 to 12.1)% (p<0.0001), Delta[oxCCO] decreased by 0.24 (0.06 to 0.28) micromoles/l (p<0.01), total hemoglobin concentration increased by 2.83 (2.27 to 4.46) micromoles/l (p<0.0001), and change in hemoglobin difference concentration (Delta[Hbdiff]=Delta[HbO(2)]-Delta[HHb]) decreased by 12.72 (11.32 to 16.34) micromoles/l (p<0.0001). Change in ecDO(2) correlated with Delta[oxCCO] (r=0.78, p<0.001), but not with either change in total hemoglobin concentration or Delta[Hbdiff]. This is the first description of cerebral Delta[oxCCO] during hypoxemia in healthy adults. Studies are ongoing to investigate the clinical relevance of this signal in patients with traumatic brain injury.

The effect on cerebral tissue oxygenation index of changes in the concentrations of inspired oxygen and end-tidal carbon dioxide in healthy adult volunteers.

BACKGROUND:A variety of near-infrared spectroscopy devices can be used to make noninvasive measurements of cerebral tissue oxygen saturation (ScO2). The ScO2 measured by the NIRO 300 spectrometer (Hamamatsu Photonics, Japan) is called the cerebral tissue oxygenation index (TOI) and is an assessment of the balance between cerebral oxygen delivery and utilization. We designed this study to investigate the effect of systemic and intracranial physiological changes on TOI. METHODS:Fifteen healthy volunteers were studied during isocapneic hyperoxia and hypoxemia, and normoxic hypercapnea and hypocapnea. Absolute cerebral TOI and changes in oxy- and deoxyhemoglobin concentrations were measured using a NIRO 300 spectrometer. Changes in arterial oxygen saturation (Sao2), ETco2, heart rate, mean arterial blood pressure (MBP), and middle cerebral artery blood flow velocity (Vmca) were also measured during these physiological challenges. Changes in cerebral blood volume (CBV) were subsequently calculated from changes in total cerebral hemoglobin concentration. RESULTS:Baseline TOI was 67.3% with an interquartile range (IQR) of 65.2%–71.9%. Hypoxemia was associated with a median decrease in TOI of 7.1% (IQR −9.1% to −5.4%) from baseline (P < 0.0001) and hyperoxia with a median increase of 2.3% (IQR 2.0%–2.5%) (P < 0.0001). Hypocapnea caused a reduction in TOI of 2.1% (IQR −3.3% to −1.3%) from baseline (P < 0.0001) and hypercapnea an increase of 2.6% (IQR 1.4%–3.7%) (P < 0.0001). Changes in Sao2 (P < 0.0001), ETco2 (P < 0.0001), CBV (P = 0.0003), and MBP (P = 0.03) were significant variables affecting TOI. Changes in Vmca (P = 0.7) and heart rate (P = 0.2) were not significant factors. CONCLUSION:TOI is an easy-to-monitor variable that provides real-time, multisite, and noninvasive assessment of the balance between cerebral oxygen delivery and utilization. However, TOI is a complex variable that is affected by Sao2 and ETco2, and, to a lesser extent, by MBP and CBV. Clinicians need to be aware of the systemic and cerebral physiological changes that can affect TOI to interpret changes in this variable during clinical monitoring.

Measurement of Frontal Lobe Functional Activation and Related Systemic Effects: A Near-Infrared Spectroscopy Investigation

Near-infrared spectroscopy (NIRS) has been used to measure changes in cerebral oxy- and deoxy- haemoglobin (delta[HbO2], delta[HHb]) in response to functional activation. It has been previously reported that during functional activation of the motor cortex heart rate increases. The aim of this study was to investigate systemic changes during functional activation of the frontal cortex. The responses to anagram presentations with varying difficulty (4-Letters and 7-Letters) over a 6 minute period were recorded. A Hamamatsu NIRO 200 NIRS system recorded delta[HbO2] and delta[HHb] using the modified Beer Lambert law (MBL) and tissue oxygenation index (TOI) employing spatial resolved spectroscopy (SRS) over the left and right frontal hemisphere. Mean blood pressure (MBP) and heart rate (HR) were measured continuously. Nine young healthy volunteers (mean age 23) were included in the analysis. Significant task related changes were observed in both the NIRS and systemic signals during the anagram solving with increases in [HbO2] and [HHb] accompanied by changes in MBP and HR. The [HbO2] and [HHb] signals measured over the frontal region were found to have a varying association with the MBP signal across different volunteers. The effect of these systemic changes on measured NIRS signals must be considered