Variability Of Hemodynamic Responses Research Articles

Evaluation of Cardiovascular Response to Isometric Handgrip Exercise in Obese Individuals.

Background The variability in hemodynamic responses to isometric handgrip exercise in people with different body mass indices (BMIs) is noteworthy due to the frequent incidence of hypertension, obesity, and related cardiovascular illnesses in India. This investigation may be necessary to anticipate and prevent excessive heart strain during static activities. Therefore, this study aimed to evaluate the impact of isometric handgrip exercise on cardiorespiratory responses in an Indian population with varying BMI levels. The objective was to compare the cardiovascular responses of obese and non-obese individuals to an isometric handgrip exercise test (heart rate, systolic blood pressure, diastolic blood pressure, rate pressure product, and mean arterial pressure). Methodology This study was conducted from April 2021 to October 2022. Measurements were obtained using a pedestal-style weighing scale with a maximum capacity of 120 kg and an accuracy of 100 g at the Department of Physiology, Indira Gandhi Institute of Medical Sciences, Patna. Sphygmomanometer was used for measuring blood pressure, and a stopwatch was used to time the duration of each prolonged isometric contraction performed by the participants using a handgrip dynamometer. Baseline measurements of heart rate, blood pressure, cardiac output, and heart rate variability were done during the final three minutes of the rest phase and once more throughout the 10-minute recovery period that followed the isometric handgrip exercise. Results The average heart rate increased during the isometric handgrip exercise in the obese group (13.02 ± 1.88 beats per minute). Systolic blood pressure increased by 16.40 ± 2.65 mmHg and 23.66 ± 3.14 mmHg in the obese group and the normal weight group, respectively. The diastolic blood pressure increased similarly in the overweight and normal weight groups, measuring 18.64 ± 3.63 mmHg and 12.14 ± 1.95 mmHg, respectively. Furthermore, the mean blood pressure increased by 20.45 ± 3.13 mmHg and 13.67 ± 1.64 mmHg, respectively, both in the normal and overweight groups. Conclusions Obese individuals had greater resting heart rates, systolic blood pressure, and diastolic blood pressure than non-obese individuals. Following an isometric handgrip workout, non-obese individuals reported greater increases in heart rate, systolic blood pressure, and diastolic blood pressure than obese individuals.

Intersubject Variability in Cerebrovascular Hemodynamics and Systemic Physiology during a Verbal Fluency Task under Colored Light Exposure: Clustering of Subjects by Unsupervised Machine Learning.

There is large intersubject variability in cerebrovascular hemodynamic and systemic physiological responses induced by a verbal fluency task (VFT) under colored light exposure (CLE). We hypothesized that machine learning would enable us to classify the response patterns and provide new insights into the common response patterns between subjects. In total, 32 healthy subjects (15 men and 17 women, age: 25.5 ± 4.3 years) were exposed to two different light colors (red vs. blue) in a randomized cross-over study design for 9 min while performing a VFT. We used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach to measure cerebrovascular hemodynamics and oxygenation at the prefrontal cortex (PFC) and visual cortex (VC) concurrently with systemic physiological parameters. We found that subjects were suitably classified by unsupervised machine learning into different groups according to the changes in the following parameters: end-tidal carbon dioxide, arterial oxygen saturation, skin conductance, oxygenated hemoglobin in the VC, and deoxygenated hemoglobin in the PFC. With hard clustering methods, three and five different groups of subjects were found for the blue and red light exposure, respectively. Our results highlight the fact that humans show specific reactivity types to the CLE-VFT experimental paradigm.

The Role of Systemic Physiology in Individual Hemodynamic Responses Measured on the Head Due to Long-Term Stimulation Involving Colored Light Exposure and a Cognitive Task: An SPA-fNIRS Study.

In our previous investigations using systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) neuroimaging, we found larger variability between subjects in changes of cerebral hemodynamics and oxygenation induced by an intricate experimental paradigm involving colored light exposure and a cognitive task. We aimed to investigate the role the activity of the systemic physiology has on individual variations in the fNIRS data. Thirty-two healthy subjects (17 female, 15 male and age: 25.5 ± 4.3 years) were exposed to blue and red light for 9 min (colored light exposure, CLE) while performing a verbal fluency task (VFT). We found that (i), at the group level, the visual cortex showed a stronger deoxyhemoglobin concentration response during blue light exposure than during red light exposure, and (ii) this relationship was influenced by individually different baseline blood pressure values. Furthermore, we found other correlations between changes in fNIRS signals and changes in systemic physiology. Our study demonstrates the usefulness and necessity of the SPA-fNIRS approach to gain insights into the individual variability of hemodynamic responses measured with fNIRS, especially in the case of an intricate experimental paradigm (i.e., CLE-VFT) as used in our study.

Individual Differences in Hemodynamic Responses Measured on the Head Due to a Long-Term Stimulation Involving Colored Light Exposure and a Cognitive Task: A SPA-fNIRS Study.

When brain activity is measured by neuroimaging, the canonical hemodynamic response (increase in oxygenated hemoglobin ([O2Hb]) and decrease in deoxygenated hemoglobin ([HHb]) is not always seen in every subject. The reason for this intersubject-variability of the responses is still not completely understood. This study is performed with 32 healthy subjects, using the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. We investigate the intersubject variability of hemodynamic and systemic physiological responses, due to a verbal fluency task (VFT) under colored light exposure (CLE; blue and red). Five and seven different hemodynamic response patterns were detected in the subgroup analysis of the blue and red light exposure, respectively. We also found that arterial oxygen saturation and mean arterial pressure were positively correlated with [O2Hb] at the prefrontal cortex during the CLE-VFT independent of the color of light and classification of the subjects. Our study finds that there is substantial intersubject-variability of cerebral hemodynamic responses, which is partially explained by subject-specific systemic physiological changes induced by the CLE-VFT. This means that both subgroup analyses and the additional assessment of systemic physiology are of crucial importance to achieve a comprehensive understanding of the effects of a CLE-VFT on human subjects.

Athlete-Specific Neural Strategies under Pressure: A fNIRS Pilot Study.

(1) Background: Stress and pressure during competition and training impair athletes’ performance in sports. However, the influence of mental stress on the prefrontal cortex (PFC) functioning in an athlete during the visual simulation task is unknown. The purpose of this pilot study was to investigate hemodynamic responses during the visual-simulation task that induces pressure and stress using functional near-infrared spectroscopy. (2) Methods: Ten archers and ten non-athlete collegiate students performed a visual-simulation task. Participants’ current stress levels were collected using a visual analog scale before and after the task. Average oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (HbT) levels and their variability (standard deviation (SD) HbO, SD HbR, and SD HbT) were computed to compare the neural efficiency between athlete and non-athlete. (3) Results: In general, both groups exhibited increased stress levels after the simulation task, and there was no group difference in overall average hemodynamic response from PFC and dorsolateral prefrontal cortex (DLPFC). While the average hemodynamic response level did not differ between groups, variability in hemodynamic responses from the archer group showed a more stable pattern than the non-athlete group. (4) Conclusion: Under this experimental setting, decreasing the variability in hemodynamic responses during the visual simulation, potentially via stabilizing the fluctuation of PFC, was characterized by the stress-related compensatory neural strategy of elite archers.

White Matter Neuroplasticity: Motor Learning Activates the Internal Capsule and Reduces Hemodynamic Response Variability.

Numerous studies have noted the importance of white matter changes in motor learning, but existing literature only focuses on structural and microstructural MRI changes, as there are limited tools available for in vivo investigations of white matter function. One method that has gained recent prominence is the application of blood oxygen level dependent (BOLD) fMRI to white matter, with high-field scanners now being able to better detect the smaller hemodynamic changes present in this tissue type compared to those in the gray matter. However, fMRI techniques have yet to be applied to investigations of neuroplastic change with motor learning in white matter. White matter function represents an unexplored component of neuroplasticity and is essential for gaining a complete understanding of learning-based changes occurring throughout the whole brain. Twelve healthy, right-handed participants completed fine motor and gross motor tasks with both hands, using an MRI compatible computer mouse. Using a crossover design along with a prior analysis approach to establish WM activation, participants received a baseline scan followed by 2 weeks of training, returning for a midpoint and endpoint scan. The motor tasks were designed to be selectively difficult for the left hand, leading to a training effect only in that condition. Analysis targeted the comparison and detection of training-associated right vs left hand changes. A statistically significant improvement in motor task score was only noted for the left-hand motor condition. A corresponding change in the temporal characteristics of the white matter hemodynamic response was shown within only the right corticospinal tract. The hemodynamic response exhibited a reduction in the dispersion characteristics after the training period. To our knowledge, this is the first report of MRI detectable functional neuroplasticity in white matter, suggesting that modifications in temporal characteristics of white matter hemodynamics may underlie functional neuroplasticity in this tissue.

Optical measurement of microvascular oxygenation and blood flow responses in awake mouse cortex during functional activation

The cerebral cortex has a number of conserved morphological and functional characteristics across brain regions and species. Among them, the laminar differences in microvascular density and mitochondrial cytochrome c oxidase staining suggest potential laminar variability in the baseline O2 metabolism and/or laminar variability in both O2 demand and hemodynamic response. Here, we investigate the laminar profile of stimulus-induced intravascular partial pressure of O2 (pO2) transients to stimulus-induced neuronal activation in fully awake mice using two-photon phosphorescence lifetime microscopy. Our results demonstrate that stimulus-induced changes in intravascular pO2 are conserved across cortical layers I–IV, suggesting a tightly controlled neurovascular response to provide adequate O2 supply across cortical depth. In addition, we observed a larger change in venular O2 saturation (ΔsO2) compared to arterioles, a gradual increase in venular ΔsO2 response towards the cortical surface, and absence of the intravascular “initial dip” previously reported under anesthesia. This study paves the way for quantification of layer-specific cerebral O2 metabolic responses, facilitating investigation of brain energetics in health and disease and informed interpretation of laminar blood oxygen level dependent functional magnetic resonance imaging signals.

Sustained versus instantaneous connectivity differentiates cognitive functions of processing speed and episodic memory.

Synchrony of brain activity over time describes the functional connectivity between brain regions but does not address the temporal component of this relationship. We propose a complementary method of analysis by introducing the width of cross-correlation curves between functional MRI (fMRI) time series as a metric of the relative duration of synchronous activity between brain regions, or "sustained connectivity". Using resting-state fMRI, cognitive, and demographics data from 1,003 subjects included in the Human Connectome Project, we find that sustained connectivity is a reproducible trait in individuals, heritable, more transient in females, and shows changes with age in early adulthood. Sustained connectivity in sensory brain regions is specifically associated with differences in processing speed across subjects, particularly in men. In contrast, traditional functional connectivity was correlated with a measure of episodic memory, but not with processing speed. Individual differences in hemodynamic response function (HRF) are closely approximated by sustained connectivity and width of the HRF is also correlated with processing speed across individuals, suggesting that variability in hemodynamic response may be influenced by transient versus sustained neural activity rather than simply differences in vascularity and signal transduction. Sustained connectivity may provide new opportunities to study brain dynamics in clinical populations.

Neurobiology, not artifacts: Challenges and guidelines for imaging the high risk infant

The search for the brain-basis of atypical development in human infants is challenging because the process of imaging and the generation of the MR signal itself relies on assumptions that reflect biophysical properties of the brain tissue. These assumptions are not inviolate, have been questioned by recent empirical evidence from high risk infant-sibling studies, and to date remain largely underexamined at the between-group level. In particular, I consider recent work showing that infants at High vs. Low familial risk (HR vs. LR, respectively) for developing Autism Spectrum Disorders (ASD) have atypical patterns of head movements during an MR scan that are functionally important—they are linked to future learning trajectories in toddlerhood. Addressing head movement issues in neuroimaging analyses in infant research as well as understanding the causes of these movements from a developmental perspective requires acknowledging the complexity of this endeavor. For example, head movement signatures in infants can interact with experimental task conditions (such as listening to language compared to sleeping), autism risk, and age. How can new knowledge about newborns' individual, subject-specific behavioral differences which may impact MR signal acquisition and statistical inference ignite critical thinking for the field of infant brain imaging across the spectrum of typical and atypical development? Early behavioral differences between HR and LR infant cohorts that are often examples of “artifactual” confounds in MR work provide insight into nascent neurobiological differences, including biophysical tissue properties and hemodynamic response variability, in these and related populations at risk for atypical development. Are these neurobiological drivers of atypical development? This work identifies important knowledge gaps and suggests guidelines at the leading edge of baby imaging science to transform our understanding of atypical brain development in humans. The precise study of the neurobiological underpinnings of atypical development in humans calls for approaches including quantitative MRI (qMRI) pulse sequences, multi-modal imaging (including DTI, MRS, as well as MEG), and infant-specific HRF shapes when modeling BOLD signal.

Common genetic polymorphisms of adenosine A2A receptor do not influence response to regadenoson.

Hemodynamic response to regadenoson varies greatly, and underlying mechanisms for variability are poorly understood. We hypothesized that five common variants of adenosine A2A receptor (ADORA2A) are associated with altered response to regadenoson. Consecutive subjects (n = 357) undergoing resting regadenoson nuclear stress imaging were enrolled. Genotyping was performed using Taqman-based assays for rs5751862, rs2298383, rs3761422, rs2267076 and rs5751876. There was no significant difference in heart rate or blood pressure between different genotypes following regadenoson administration. There was also no significant difference in myocardial ischemia detected by nuclear perfusion imaging as defined by summed difference score, or in self-reported side effects among the genotypes tested. The common A2A variants studied are not associated with variability in hemodynamic response to regadenoson or variability in detection of ischemia with nuclear perfusion stress imaging.

Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex

The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.

Cortical Sensorimotor Processing of Painful Pressure in Patients with Chronic Lower Back Pain-An Optical Neuroimaging Study using fNIRS.

In this study we investigated sensorimotor processing of painful pressure stimulation on the lower back of patients with chronic lower back pain (CLBP) by using functional near-infrared spectroscopy (fNIRS) to measure changes in cerebral hemodynamics and oxygenation. The main objectives were whether patients with CLBP show different relative changes in oxy- and deoxyhemoglobin ([O2Hb] and [HHb]) in the supplementary motor area (SMA) and primary somatosensory cortex (S1) compared to healthy controls (HC). Twelve patients with CLBP (32 ± 6.1 years; range: 24–44 years; nine women) and 20 HCs (33.5 ± 10.7 years; range 22–61 years; eight women) participated in the study. Painful and non-painful pressure stimulation was exerted with a thumb grip perpendicularly to the spinous process of the lumbar spine. A force sensor was attached at the spinous process in order to control pressure forces. Tactile stimulation was realized by a one-finger brushing. Hemodynamic changes in the SMA and S1 were measured bilaterally using a multi-channel continuous wave fNIRS imaging system and a multi-distant probe array. Patients with CLBP showed significant stimulus-evoked hemodynamic responses in [O2Hb] only in the right S1, while the HC exhibited significant [O2Hb] changes bilaterally in both, SMA and S1. However, the group comparisons revealed no significant different hemodynamic responses in [O2Hb] and [HHb] in the SMA and S1 after both pressure stimulations. This non-significant result might be driven by the high inter-subject variability of hemodynamic responses that has been observed within the patients group. In conclusion, we could not find different stimulus-evoked hemodynamic responses in patients with CLBP compared to HCs. This indicates that neither S1 nor the SMA show a specificity for CLBP during pressure stimulation on the lower back. However, the results point to a potential subgrouping regarding task-related cortical activity within the CLBP group; a finding worth further research.

Pros and Cons of Using the Informed Basis Set to Account for Hemodynamic Response Variability with Developmental Data.

Conventional analysis of functional magnetic resonance imaging (fMRI) data using the general linear model (GLM) employs a neural model convolved with a canonical hemodynamic response function (HRF) peaking 5 s after stimulation. Incorporation of a further basis function, namely the canonical HRF temporal derivative, accounts for delays in the hemodynamic response to neural activity. A population that may benefit from this flexible approach is children whose hemodynamic response is not yet mature. Here, we examined the effects of using the set based on the canonical HRF plus its temporal derivative on both first- and second-level GLM analyses, through simulations and using developmental data (an fMRI dataset on proprioceptive mapping in children and adults). Simulations of delayed fMRI first-level data emphasized the benefit of carrying forward to the second-level a derivative boost that combines derivative and nonderivative beta estimates. In the experimental data, second-level analysis using a paired t-test showed increased mean amplitude estimate (i.e., increased group contrast mean) in several brain regions related to proprioceptive processing when using the derivative boost compared to using only the nonderivative term. This was true especially in children. However, carrying forward to the second-level the individual derivative boosts had adverse consequences on random-effects analysis that implemented one-sample t-test, yielding increased between-subject variance, thus affecting group-level statistic. Boosted data also presented a lower level of smoothness that had implication for the detection of group average activation. Imposing soft constraints on the derivative boost by limiting the time-to-peak range of the modeled response within a specified range (i.e., 4–6 s) mitigated these issues. These findings support the notion that there are pros and cons to using the informed basis set with developmental data.

Amplitude variability over trials in hemodynamic responses in adolescents with ADHD: The role of the anterior default mode network and the non-specific role of the striatum.

It has been suggested that intra-individual variability (IIV) in performance on attention and other cognitive tasks might be a cognitive endophenotype in individuals with ADHD. Despite robust IIV findings in behavioral data, only sparse data exist on how what type of brain dysfunction underlies variable response times. In this study, we asked whether ADHD IIV in reaction time on a commonly-used test of attention might be related to variation in hemodynamic responses (HRs) observed trial-to-trial. Based on previous studies linking IIV to regions within the “default mode” network (DMN), we predicted that adolescents with ADHD would have higher HR variability in the DMN compared with controls, and this in turn would be related to behavioral IIV. We also explored the influence of social anxiety on HR variability in ADHD as means to test whether higher arousal associated with high trait anxiety would affect the neural abnormalities. We assessed single-trial variability of HRs, estimated from fMRI event-related responses elicited during an auditory oddball paradigm in adolescents with ADHD and healthy controls (11–18 years old; N = 46). Adolescents with ADHD had higher HR variability compared with controls in anterior regions of the DMN. This effect was specific to ADHD and not associated with traits of age, IQ and anxiety. However, an ADHD effect of higher HR variability also appeared in a basal ganglia network, but for these brain regions the relationships of HR variability and social anxiety levels were more complex. Performance IIV correlated significantly with variability of HRs in both networks. These results suggest that assessment of trial-to-trial HR variability in ADHD provides information beyond that detectable through analysis of behavioral data and average brain activation levels, revealing specific neural correlates of a possible ADHD IIV endophenotype.

Variability in prefrontal hemodynamic response during exposure to repeated self-selected music excerpts, a near-infrared spectroscopy study.

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes.

Abstract 17254: Adenosine A2A Receptor Polymorphisms and Response to Regadenoson

Introduction: Activation of adenosine A2A receptors induces coronary vasodilation and sympathetic activation. Regadenoson is an A2A agonist used in pharmacologic cardiac nuclear stress testing, and exhibits large variability in hemodynamic response and incidence of side effects. Common genetic variants of A2A have been associated with functional differences in neurological phenotypes. Hypothesis: We hypothesized that common polymorphisms of A2A may influence response to regadenoson during cardiac stress testing. Methods: We prospectively enrolled 268 patients undergoing resting regadenoson stress testing. Five common A2A receptor variants were analyzed by Taqman genotyping assay. SPECT technetium nuclear stress tests were performed and analyzed using the 17-segment model. Blood pressure and heart rate changes were recorded prospectively after administration of regadenoson. Results: Variants of A2A were associated with significant differences in heart rate (HR), peak systolic blood pressure (SBP), and summed stress score (Table). The association of rs2298383 (minor allele frequency (MAF)=0.49), rs5751876 (MAF=0.39), and rs3761422 (MAF=0.4) with heart rate and blood pressure at rest and peak remained significant after multivariate adjustment for demographics, race, and clinical variables. Similarly, carrier status of rs2298383, rs5751876, rs3761422, and rs2267076 (MAF=0.37) remained significantly associated with summed stress score (SSS) after multivariate adjustment. Conclusion: Common genetic variants of A2A may be associated with variability in heart rate and blood pressure response to regadenoson and extent of ischemia on nuclear myocardial perfusion imaging. Further studies are necessary to examine the influence of A2A receptor variants on diagnostic sensitivity of regadenoson nuclear stress testing.

Increased sensitivity of fast BOLD fMRI with a subject-specific hemodynamic response function and application to epilepsy

Activation detection in functional Magnetic Resonance Imaging (fMRI) typically assumes the hemodynamic response to neuronal activity to be invariant across brain regions and subjects. Reports of substantial variability of the morphology of blood-oxygenation-level-dependent (BOLD) responses are accumulating, suggesting that the use of a single generic model of the expected response in general linear model (GLM) analyses does not provide optimal sensitivity due to model misspecification. Relaxing assumptions of the model can limit the impact of hemodynamic response function (HRF) variability, but at a cost on model parsimony. Alternatively, better specification of the model could be obtained from a priori knowledge of the HRF of a given subject, but the effectiveness of this approach has only been tested on simulation data. Using fast BOLD fMRI, we characterized the variability of hemodynamic responses to a simple event-related auditory-motor task, as well as its effect on activation detection with GLM analyses. We show the variability to be higher between subjects than between regions and variation in different regions to correlate from one subject to the other. Accounting for subject-related variability by deriving subject-specific models from responses to the task in some regions lead to more sensitive detection of responses in other regions. We applied the approach to epilepsy patients, where task-derived patient-specific models provided additional information compared to the use of a generic model for the detection of BOLD responses to epileptiform activity identified on scalp electro-encephalogram (EEG). This work highlights the importance of improving the accuracy of the model for detecting neuronal activation with fMRI, and the fact that it can be done at no cost to model parsimony through the acquisition of independent a priori information about the hemodynamic response.

A reference-channel based methodology to improve estimation of event-related hemodynamic response from fNIRS measurements

Functional near-infrared spectroscopy (fNIRS) uses near-infrared light to measure cortical concentration changes in oxygenated (HbO) and deoxygenated hemoglobin (HbR) held to be correlated with cognitive activity. Providing a parametric depiction of such changes in the classic form of stimulus-evoked hemodynamic responses (HRs) can be attained with this technique only by solving two problems. One problem concerns the separation of informative optical signal from structurally analogous noise generated by a variety of spurious sources, such as heart beat, respiration, and vasomotor waves. Another problem pertains to the inherent variability of HRs, which is notoriously contingent on the type of experiment, brain region monitored, and human phenotype. A novel method was devised in the present context to solve both problems based on a two-step algorithm combining the treatment of noise-only data extrapolated from a reference-channel and a Bayesian filter applied on a per-trial basis. The present method was compared to two current methods based on conventional averaging, namely, a typical averaging method and an averaging method implementing the use of a reference-channel. The result of the comparison, carried out both on artificial and real data, revealed a sensitive accuracy improvement in HR estimation using the present method relative to each of the other methods.

Inter-Trial Variability in Sensory-Evoked Cortical Hemodynamic Responses: The Role of the Magnitude of Pre-Stimulus Fluctuations

Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, stimulus-evoked hemodynamic responses display considerable inter-trial variability and the sources of this variability are poorly understood. One of the sources of this response variation could be ongoing spontaneous hemodynamic fluctuations. We recently investigated this issue by measuring cortical hemodynamics in response to sensory stimuli in anesthetized rodents using 2-dimensional optical imaging spectroscopy. We suggested that sensory-evoked cortical hemodynamics displayed distinctive response characteristics and magnitudes depending on the phase of ongoing fluctuations at stimulus onset due to a linear superposition of evoked and ongoing hemodynamics (Saka et al., 2010). However, the previous analysis neglected to examine the possible influence of variability of the size of ongoing fluctuations. Consequently, data were further analyzed to examine whether the size of pre-stimulus hemodynamic fluctuations also influenced the magnitude of subsequent stimulus-evoked responses. Indeed, in the case of all individual trials, a moderate correlation between the size of the pre-stimulus fluctuations and the magnitudes of the subsequent sensory-evoked responses were observed. However, different correlations between the size of the pre-stimulus fluctuations and magnitudes of the subsequent sensory-evoked cortical hemodynamic responses could be observed depending on their phase at stimulus onset. These analyses suggest that both the size and phase of pre-stimulus fluctuations in cortical hemodynamics contribute to inter-trial variability in sensory-evoked responses.

Nonlinear hemodynamic responses in human epilepsy: A multimodal analysis with fNIRS-EEG and fMRI-EEG

Functional magnetic resonance imaging (fMRI) combined with electroencephalography (fMRI-EEG) is a neuroimaging technique based on the blood oxygenation level dependent (BOLD) signal which has been shown to be useful in the study of epilepsy for the localization of the epileptogenic focus. Functional near-infrared spectroscopy (fNIRS) combined with EEG (fNIRS-EEG) is another imaging technique based on the measurement of oxygenated and deoxygenated hemoglobin with complementary clinical potential in epilepsy, for continuous patient monitoring, language lateralization, and focus localization.In this work fMRI-EEG and fNIRS-EEG are used to quantify nonlinear hemodynamic responses in three cases of human refractory focal epilepsy, by using the Volterra kernel expansion up to second order. Prior to analyzing real data, extensive simulations are carried out to show that nonlinearities are estimable. The Volterra methodology is then applied to multimodal data recorded from 3 epileptic patients selected for their frequent spiking activity. Care is taken to account for variability of hemodynamic responses due to other causes than Volterra nonlinearities. Statistically significant nonlinearities are observed for all patients and all modalities. Good concordance between fNIRS and fMRI is found for both the amplitude of the Volterra responses, and, with limitations, in the localization of the epileptic focus and regions of inverted responses (negative BOLD signals). In one patient, Volterra nonlinearities allowed epileptic focus identification with fMRI, while analyses without nonlinearities failed to see it. In simulations when nonlinearities were included, analysis without Volterra nonlinearities performed poorly. These two observations suggest routinely checking for nonlinearities in functional imaging of patients presenting with frequent spikes.