Non-neural BOLD variability in block and event-related paradigms

Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen level-dependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability.     

Direct measurement of oxygen extraction with fMRI using 6% CO2 inhalation

The blood-oxygenation-level-dependent (BOLD) signal is an indirect hemodynamic signal that is sensitive to cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen. Therefore, the BOLD signal amplitude and dynamics cannot be interpreted unambiguously without additional physiological measurements, and thus, there remains a need for a functional magnetic resonance imaging (fMRI) signal, which is more closely related to the underlying neuronal activity. In this study, we measured CBF with continuous arterial spin labeling, CBV with an exogenous contrast agent and BOLD combined with intracortical electrophysiological recording in the primary visual cortex of the anesthetized monkey. During inhalation of 6% CO2, it was observed that CBF and CBV are not further increased by a visual stimulus, although baseline CBF for 6% CO2 is below the maximal value of CBF. In contrast, the electrophysiological response to the stimulation was found to be preserved during hypercapnia. As a consequence, the simultaneously measured BOLD signal responds negatively to a visual stimulation for 6% CO2 inhalation in the same voxels responding positively during normocapnia. These observations suggest that the fMRI response to a sensory stimulus for 6% CO2 inhalation occurs in the absence of a hemodynamic response, and it therefore directly reflects oxygen extraction into the tissue.     

Regional homogeneity of resting-state fMRI contributes to both neurovascular and task activation variations

The task induced blood oxygenation level dependent signal changes observed using functional magnetic resonance imaging (fMRI) are critically dependent on the relationship between neuronal activity and hemodynamic response. Therefore, understanding the nature of neurovascular coupling is important when interpreting fMRI signal changes evoked via task. In this study, we used regional homogeneity (ReHo), a measure of local synchronization of the BOLD time series, to investigate whether the similarities of one voxel with the surrounding voxels are a property of neurovascular coupling. FMRI scans were obtained from fourteen subjects during bilateral finger tapping (FTAP), digit–symbol substitution (DSST) and periodic breath holding (BH) paradigm. A resting-state scan was also obtained for each of the subjects for 4 min using identical imaging parameters. Inter-voxel correlation analyses were conducted between the resting-state ReHo, resting-state amplitude of low frequency fluctuations (ALFF), BH responses and task activations within the masks related to task activations. There was a reliable mean voxel-wise spatial correlation between ReHo and other neurovascular variables (BH responses and ALFF). We observed a moderate correlation between ReHo and task activations (FTAP: r = 0.32; DSST: r = 0.22) within the task positive network and a small yet reliable correlation within the default mode network (DSST: r = − 0.08). Subsequently, a linear regression was used to estimate the contribution of ReHo, ALFF and BH responses to the task activated voxels. The unique contribution of ReHo was minimal. The results suggest that regional synchrony of the BOLD activity is a property that can explain the variance of neurovascular coupling and task activations; but its contribution to task activations can be accounted for by other neurovascular factors such as the ALFF.     

Simultaneous BOLD/perfusion measurement using dual-echo FAIR and UNFAIR: sequence comparison at 1.5T and 3.0T.

Functional MRI (fMRI) studies designed for simultaneously measuring Blood Oxygenation Level Dependent (BOLD) and Cerebral Blood Flow (CBF) signal often employ the standard Flow Alternating Inversion Recovery (FAIR) technique. However, some sensitivity is lost in the BOLD data due to inherent T1 relaxation. We sought to minimize the preceding problem by employing a modified UN-inverted FAIR (UNFAIR) technique, which (in theory) should provide identical CBF signal as FAIR with minimal degradation of the BOLD signal. UNFAIR BOLD maps acquired from human subjects (n = 8) showed significantly higher mean z-score of approximately 17% (p < 0.001), and number of activated voxels at 1.5T. On the other hand, the corresponding FAIR perfusion maps were superior to the UNFAIR perfusion maps as reflected in a higher mean z-score of approximately 8% (p = 0.013), and number of activated voxels. The reduction in UNFAIR sensitivity for perfusion is attributed to increased motion sensitivity related to its higher background signal, and, T2 related losses from the use of an extra inversion pulse. Data acquired at 3.0T demonstrating similar trends are also presented.     

Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T

Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (P<10(-7)) and area (P<10(-8)) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties.     

Component structure of event-related fMRI responses in the different neurovascular compartments

In most functional magnetic resonance imaging (fMRI) studies, brain activity is localized by observing changes in the blood oxygenation level-dependent (BOLD) signal that are believed to arise from capillaries, venules and veins in and around the active neuronal population. However, the contribution from veins can be relatively far downstream from active neurons, thereby limiting the ability of BOLD imaging methods to precisely pinpoint neural generators. Hemodynamic measures based on apparent diffusion coefficients (ADCs) have recently been used to identify more upstream functional blood flow changes in the capillaries, arterioles and arteries. In particular, we recently showed that, due to the complementary vascular sensitivities of ADC and BOLD signals, the voxels conjointly activated by both measures may identify the capillary networks of the active neuronal areas. In this study, we first used simultaneously acquired ADC and BOLD functional imaging signals to identify brain voxels activated by ADC only, by both ADC and BOLD and by BOLD only, thereby delineating voxels relatively dominated by the arterial, capillary, and draining venous neurovascular compartments, respectively. We then examined the event-related fMRI BOLD responses in each of these delineated neurovascular compartments, hypothesizing that their event-related responses would show different temporal componentries. In the regions activated by both the BOLD and ADC contrasts, but not in the BOLD-only areas, we observed an initial transient signal reduction (an initial dip), consistent with the local production of deoxyhemoglobin by the active neuronal population. In addition, the BOLD-ADC overlap areas and the BOLD-only areas showed a clear poststimulus undershoot, whereas the compartment activated by only ADC did not show this component. These results indicate that using ADC contrast in conjunction with BOLD imaging can help delineate the various neurovascular compartments, improve the localization of active neural populations, and provide insight into the physiological mechanisms underlying the hemodynamic signals.     

Neonatal auditory activation detected by functional magnetic resonance imaging

The objective of this study was to detect auditory cortical activation in non-sedated neonates employing functional magnetic resonance imaging (fMRI). Using echo-planar functional brain imaging, subjects were presented with a frequency-modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices running parallel to the superior temporal gyrus. Twenty healthy neonates (13 term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level-dependent (BOLD) signal in response to auditory stimulus was detected in all 4 adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated increased signal in the superior temporal regions during auditory stimulation. In contrast, signal decreases were detected during auditory stimulation in 9 of 14 newborns with BOLD response. fMRI can be used to detect brain activation with auditory stimulation in human infants.     

Post-stimulus response in hemodynamics observed by functional magnetic resonance imaging--difference between the primary sensorimotor area and the supplementary motor area

The blood oxygen level dependency (BOLD) contrast is a useful tool for functional neuroimaging based on the hemodynamic response to neuronal activation. We observed different hemodynamic responses in the BOLD signal between the primary sensorimotor area (SM1) and the supplementary motor area (SMA) in the sequential finger movement task. In the SMA, a stronger initial overshoot and a post-stimulus overshoot were observed. It was hypothesized from the time course analysis that the stronger initial overshoot reflected the activation of the SMA for motor control programming in the initial phase. Although the post-stimulus overshoot may be partially explained by cerebral blood flow (CBF) cerebral blood volume (CBV) uncoupling, its mechanism remained unknown. In the SM1, only the initial overshoot was observed and the level of BOLD signal was almost constant after the initial overshoot during the task period. These observations suggested that the BOLD signal is characterized by both CBF-CBV uncoupling and the neuronal activation characteristics in each region.     

Dynamics and nonlinearities of the BOLD response at very short stimulus durations

In designing a functional imaging experiment or analyzing data, it is typically assumed that task duration and hemodynamic response are linearly related to each other. However, numerous human and animal studies have previously reported a deviation from linearity for short stimulus durations (<4 s). Here, we investigated nonlinearities of blood-oxygenation-level-dependent (BOLD) signals following visual stimulation of 5 to 1000 ms duration at two different luminance levels in human subjects. It was found that (a) a BOLD response to stimulus durations as short as 5 ms can be reliably detected; this stimulus duration is shorter than employed in any previous study investigating BOLD signal time courses; (b) the responses are more nonlinear than in any other previous study: the BOLD response to 1000 ms stimulation is only twice as large as the BOLD response to 5 ms stimulation although 200 times more photons were projected onto the retina; (c) the degree of nonlinearity depends on stimulus intensity; that is, nonlinearities have to be characterized not only by stimulus duration but also by stimulus features like luminance. These findings are especially of most practical importance in rapid event-related functional magnetic resonance imaging (fMRI) experimental designs. In addition, an 'initial dip' response--thought to be generated by a rapid increase in cerebral metabolic rate of oxygen metabolism (CMRO2) relative to cerebral blood flow--was observed and shown to colocalize well with the positive BOLD response. Highly intense stimulation, better tolerated by human subjects for short stimulus durations, causes early CMRO2 increase, and thus, the experimental design utilized in this study is better for detecting the initial dip than standard fMRI designs. These results and those from other groups suggest that short stimulation combined with appropriate experimental designs allows neuronal events and interactions to be examined by BOLD signal analysis, despite its slow evolution.     

An investigation of the relationship between BOLD and perfusion signal changes during epileptic generalised spike wave activity

In pathological conditions interpretation of functional magnetic resonance imaging (fMRI) results can be difficult. This is due to a reliance on the assumed coupling between neuronal activity and changes in cerebral blood flow (CBF) and oxygenation. We wanted to investigate the coupling between blood oxygen level dependant contrast (BOLD) and CBF time courses in epilepsy patients with generalised spike wave activity (GSW) to better understand the underlying mechanisms behind the EEG-fMRI signal changes observed, especially in regions of negative BOLD response (NBR). Four patients with frequent GSW were scanned with simultaneous electroencephalographic (EEG)-fMRI with BOLD and arterial spin labeling (ASL) sequences. We examined the relationship between simultaneous CBF and BOLD measurements by looking at the correlation of the two signals in terms of percentage signal change on a voxel-by-voxel basis. This method is not reliant on coincident activation. BOLD and CBF were positively correlated in patients with epilepsy during background EEG activity and GSW. The subject average value of the Delta CBF/Delta BOLD slope lay between +19 and +36 and also showed spatial variation which could indicate areas with altered vascular response. There was not a significant difference between Delta CBF/Delta BOLD during GSW, suggesting that neurovascular coupling to BOLD signal is generally maintained between states and, in particular, within areas of NBR.     

Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity

Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses.     

Comparison between end-tidal CO₂ and respiration volume per time for detecting BOLD signal fluctuations during paced hyperventilation

Respiratory motion and capnometry monitoring were performed during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) of the brain while a series of paced hyperventilation tasks were performed that caused significant hypocapnia. Respiration volume per time (RVT) and end-tidal carbon dioxide (ETCO(2)) were determined and compared for their ability to explain BOLD contrast changes in the data. A 35% decrease in ETCO(2) was observed along with corresponding changes in RVT. A best-fit ETCO(2) response function, with an average initial peak delay time of 12 s, was empirically determined. ETCO(2) data convolved with this response function was more strongly and prevalently correlated to BOLD signal changes than RVT data convolved with the corresponding respiration response function. The results suggest that ETCO(2) better models BOLD signal fluctuations in fMRI experiments with significant transient hypocapnia. This is due to hysteresis in the ETCO(2) response when moving from hypocapnia to normocapnia, compared to moving from normocapnia to hypocapnia.     

Neural and vascular variability and the fMRI-BOLD response in normal aging

Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19–27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55–71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response.     

Functional magnetic resonance imaging based on SEEP contrast: response function and anatomical specificity

Functional magnetic resonance imaging based on a non-BOLD-contrast mechanism, which we have termed "SEEP" (Signal Enhancement by Extravascular water Protons), has previously been demonstrated. Here the reproducibility of areas of activity identified with both SEEP and BOLD contrast is assessed in duplicate experiments in healthy volunteers, with relatively high resolution (1.6 mm) image data at 1.5 T. These areas of activity are equally well localized to voxels containing primarily gray matter with the two contrast mechanisms. As in previous studies, areas of SEEP activity are observed to be immediately adjacent to areas of BOLD activity, with very little overlap. The response functions were estimated for both SEEP and BOLD contrast, and are observed to be distinct. The peak SEEP response is observed to lag the BOLD response by approximately 1 s and to decay more slowly with no poststimulus undershoot. Average BOLD signal changes (GE-EPI, TE=50 ms) were observed to be 3.4+/-1.2% (mean+/-S.D.), whereas SEEP signal changes (SE-EPI, TE=23 ms) were 1.9+/-0.5%, consistent with previous studies carried out at 0.2 and 3 T. These observations provide further support for the existence of a non-BOLD-contrast mechanism for fMRI, based on changes in extravascular spin density.     

Integration of EEG source imaging and fMRI during continuous viewing of natural movies

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are noninvasive neuroimaging tools which can be used to measure brain activity with excellent temporal and spatial resolution, respectively. By combining the neural and hemodynamic recordings from these modalities, we can gain better insight into how and where the brain processes complex stimuli, which may be especially useful in patients with different neural diseases. However, due to their vastly different spatial and temporal resolutions, the integration of EEG and fMRI recordings is not always straightforward. One fundamental obstacle has been that paradigms used for EEG experiments usually rely on event-related paradigms, while fMRI is not limited in this regard. Therefore, here we ask whether one can reliably localize stimulus-driven EEG activity using the continuously varying feature intensities occurring in natural movie stimuli presented over relatively long periods of time. Specifically, we asked whether stimulus-driven aspects in the EEG signal would be co-localized with the corresponding stimulus-driven BOLD signal during free viewing of a movie. Secondly, we wanted to integrate the EEG signal directly with the BOLD signal, by estimating the underlying impulse response function (IRF) that relates the BOLD signal to the underlying current density in the primary visual area (V1). We made sequential fMRI and 64-channel EEG recordings in seven subjects who passively watched 2-min-long segments of a James Bond movie. To analyze EEG data in this natural setting, we developed a method based on independent component analysis (ICA) to reject EEG artifacts due to blinks, subject movement, etc., in a way unbiased by human judgment. We then calculated the EEG source strength of this artifact-free data at each time point of the movie within the entire brain volume using low-resolution electromagnetic tomography (LORETA). This provided for every voxel in the brain (i.e., in 3D space) an estimate of the current density at every time point. We then carried out a correlation between the time series of visual contrast changes in the movie with that of EEG voxels. We found the most significant correlations in visual area V1, just as seen in previous fMRI studies (Bartels A, Zeki, S, Logothetis NK. Natural vision reveals regional specialization to local motion and to contrast-invariant, global flow in the human brain. Cereb Cortex 2008;18(3):705–717), but on the time scale of milliseconds rather than of seconds. To obtain an estimate of how the EEG signal relates to the BOLD signal, we calculated the IRF between the BOLD signal and the estimated current density in area V1. We found that this IRF was very similar to that observed using combined intracortical recordings and fMRI experiments in nonhuman primates. Taken together, these findings open a new approach to noninvasive mapping of the brain. It allows, firstly, the localization of feature-selective brain areas during natural viewing conditions with the temporal resolution of EEG. Secondly, it provides a tool to assess EEG/BOLD transfer functions during processing of more natural stimuli. This is especially useful in combined EEG/fMRI experiments, where one can now potentially study neural-hemodynamic relationships across the whole brain volume in a noninvasive manner.     

Influence of speech stimuli intensity on the activation of auditory cortex investigated with functional magnetic resonance imaging.

Understanding the impact of variations in the acoustic signal is critical for the development of auditory and language fMRI as an experimental tool. We describe the dependence of the BOLD signal and speech intelligibility on the intensity of auditory stimuli. Eighteen subjects were imaged on a 1.5-T MRI scanner. Speech stimuli were English monosyllabic words played at five intensity levels. Intrasubject reproducibility was measured on one subject by presenting the stimulus five times at the same intensity level. Intelligibility was measured during data acquisition as subjects signaled when hearing two targets. Each functional trial consisted of four cycles (30 s off-30 s on). Five oblique slices covering primary and association auditory areas were imaged. Activated voxels were identified by cross-correlation analysis and their percent signal change (delta S) was measured. Intersubject differences in activation extent, asymmetry, and dependence on intensity were striking. Volume of activation was significantly greater in the left than in the right hemisphere. Intrasubject reproducibility for delta S was higher than for volume of activation. delta S and intelligibility showed a similar dependence on intensity suggesting that not only intensity but also intelligibility affect the fMRI signal.     

Functional phantom for fMRI: a feasibility study

Functional magnetic resonance imaging (fMRI) reveals changes in blood oxygen level-dependent (BOLD) signal after considerable processing. This paper describes the implementation and testing of an fMRI phantom where electric current applied to a thin wire within a proton-rich medium substituted BOLD distortion of the magnetic field; the scanner detects these two distortions as practically identical signal changes. The magnitude of the change depended on the current strength. The phantom has a number of possible applications. Signal changes across sessions, days, instruments and individuals could be monitored. Placing the phantom close to a subject during an fMRI experiment could allow differentiating sensitivity changes in the scanner due to instrumentation from changes in the subject's state and performance during the experiment. The spatial extent of brain activations and effects of various changes in the chain of image formation could be analyzed using current-induced "activations". Furthermore, the phantom could expedite fMRI sequence development by reducing the need to scan human subjects, who introduce uncertainty to the signal. Thus, this fMRI phantom could be useful for both cognitive fMRI studies and scanner calibration.     

Characterization of BOLD-fMRI signal during a verbal fluency paradigm in patients with intracerebral tumors affecting the frontal lobe

Previous studies have indicated that the BOLD-fMRI signal can be modified by tumor processes in close vicinity to functional brain areas. This effect has been investigated primarily for the perirolandic area but there is only a limited number of studies concerning frontal cortical regions. Therefore, the aim of the current study was to characterize BOLD-fMRI signal and activation patterns in patients with frontal brain tumors while performing a verbal fluency task. Six patients (ages 31-56 years) suffering from frontal (5 left sided and 1 right sided) intracerebral tumors were examined with fMRI while performing a verbal fluency task in a blocked paradigm design. Eight healthy volunteers served as the control group. The patients (5 right and 1 left handed) demonstrated left frontal activation which could be clearly located outside the tumor area and adjacent edema with varying degrees of additional right frontal activation. In the predominant left frontal activation cluster, the mean voxel based z-score and cluster size were not statistically different between patients and controls. The present fMRI study is indicating that language related BOLD signal changes in the frontal cortex of patients with tumors close to functional areas were comparable to the signal in normal controls. Additionally, the temporal hemodynamic response characteristic was comparable in both groups. This is an important finding consistent with PET results and corroborates the feasibility of functional mapping approaches in patients with tumors affecting the frontal lobe. Additional studies investigating alterations of the hemodynamic response depending on tumor location and histology are required in order to further elucidate the association between pathophysiology and BOLD fMRI signal.     

Effects of hypoglycemia on human brain activation measured with fMRI

Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory stimulation on brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast, which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 +/- 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects: the fractional signal change was reduced by 28 +/- 12% (P < .05). These changes were reversed when euglycemia was restored. These data provide a basis of comparison for studies that quantify hypoglycemia-related changes in fMRI activity during cognitive tasks based on visual stimuli and demonstrate that variations in blood glucose levels may modulate BOLD signals in the healthy brain.     

What the little differences between men and women tells us about the BOLD response

We analyzed the functional MRI signal of 15 men and 15 women. All had been presented with a flashed and a reversing, radial checkerboard stimulus. We investigated both positive and negative blood oxygenation level-dependent (BOLD) responses. The extent of activation and the change in the neuronal activity were examined. The former, by counting the number of activated voxels, the latter by using deltaR2* as an indicator of the change in the local deoxyhemoglobin (HbR) concentration. We examined both the positive and the negative BOLD response. Positive BOLD response: The flashed checkerboard gave rise to a larger number of activated voxels than for the reversing checkerboard. The mean number of activated pixels did not differ between men and women. The peak deltaR2* was significantly larger to the flashed than the reversing checkerboard, but did not reveal a gender-related difference. We noted an attenuation of the BOLD signal amplitude with time. This attenuation was larger in women than in men. Negative BOLD response: The attenuation was also larger for the flashed than the reversing stimulus and more pronounced in the chromatic contrast compared to the luminance contrast stimulus. The extent of activation was larger for the flashed than the reversing checkerboard, but did not differ between the sexes. The deltaR2* for the chromatic contrast checkerboard was larger in men than in women. No other significant differences were found. We conclude that the difference in the extent of activation between men and women is the result of our ability to detect activated pixels using statistical methods and not the result of a difference in the processing between the sexes.