Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.

The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes.

Coupling of cerebral blood flow and oxygen metabolism is conserved for chromatic and luminance stimuli in human visual cortex.

The ratio of the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation is a critical determinant of the magnitude of the blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). Cytochrome oxidase (CO), a key component of oxidative metabolism in the mitochondria, is non-uniformly distributed in visual area V1 in distinct blob and interblob regions, suggesting significant spatial variation in the capacity for oxygen metabolism. The goal of this study was to test whether CBF/CMRO(2) coupling differed when these subpopulations of neurons were preferentially stimulated, using chromatic and luminance stimuli to preferentially stimulate either the blob or interblob regions. A dual-echo spiral arterial spin labeling (ASL) technique was used to measure CBF and BOLD responses simultaneously in 7 healthy human subjects. When the stimulus contrast levels were adjusted to evoke similar CBF responses (mean 65.4% ± 19.0% and 64.6% ± 19.9%, respectively for chromatic and luminance contrast), the BOLD responses were remarkably similar (1.57% ± 0.39% and 1.59% ± 0.35%) for both types of stimuli. We conclude that CBF-CMRO(2) coupling is conserved for the chromatic and luminance stimuli used, suggesting a consistent coupling for blob and inter-blob neuronal populations despite the difference in CO concentration.

High efficiency multishot interleaved spiral-in/out: acquisition for high-resolution BOLD fMRI.

Growing demand for high spatial resolution blood oxygenation level dependent (BOLD) functional magnetic resonance imaging faces a challenge of the spatial resolution versus coverage or temporal resolution tradeoff, which can be addressed by methods that afford increased acquisition efficiency. Spiral acquisition trajectories have been shown to be superior to currently prevalent echo-planar imaging in terms of acquisition efficiency, and high spatial resolution can be achieved by employing multiple-shot spiral acquisition. The interleaved spiral in/out trajectory is preferred over spiral-in due to increased BOLD signal contrast-to-noise ratio (CNR) and higher acquisition efficiency than that of spiral-out or noninterleaved spiral in/out trajectories (Law & Glover. Magn Reson Med 2009; 62:829-834.), but to date applicability of the multishot interleaved spiral in/out for high spatial resolution imaging has not been studied. Herein we propose multishot interleaved spiral in/out acquisition and investigate its applicability for high spatial resolution BOLD functional magnetic resonance imaging. Images reconstructed from interleaved spiral-in and -out trajectories possess artifacts caused by differences in T2 decay, off-resonance, and k-space errors associated with the two trajectories. We analyze the associated errors and demonstrate that application of conjugate phase reconstruction and spectral filtering can substantially mitigate these image artifacts. After applying these processing steps, the multishot interleaved spiral in/out pulse sequence yields high BOLD CNR images at in-plane resolution below 1 × 1 mm while preserving acceptable temporal resolution (4 s) and brain coverage (15 slices of 2 mm thickness). Moreover, this method yields sufficient BOLD CNR at 1.5 mm isotropic resolution for detection of activation in hippocampus associated with cognitive tasks (Stern memory task). The multishot interleaved spiral in/out acquisition is a promising technique for high spatial resolution BOLD functional magnetic resonance imaging applications.

Attention strongly increases oxygen metabolic response to stimulus in primary visual cortex.

Top-down attention enhances neural processing, but its effect on metabolic activity in primary visual cortex (V1) is unclear. Combined blood flow and oxygenation measurements provide the best tool for investigating modulations of oxidative metabolism. We measured the human V1 response to a peripheral low contrast stimulus using fMRI and found a larger fractional modulation of blood flow with attention compared to the blood oxygenation level dependent (BOLD) response, thus indicating a much larger modulation of oxygen metabolism than was previously thought. These findings point to different aspects of neural activity driving flow and metabolic changes to different degrees. We propose that V1 flow is driven strongly but not exclusively by the initial sensory-driven neural activity, which dominates the response in the unattended condition, while V1 oxygen metabolism is driven strongly by the overall neural activity, which is modulated by top-down signals related to attention.

On multiple alternating steady states induced by periodic spin phase perturbation waveforms.

Direct measurement of neural currents by means of MRI can potentially open a high temporal resolution (10-100 ms) window applicable for monitoring dynamics of neuronal activity without loss of the high spatial resolution afforded by MRI. Previously, we have shown that the alternating balanced steady state imaging affords high sensitivity to weak periodic currents owing to its amplification of periodic spin phase perturbations. This technique, however, requires precise synchronization of such perturbations to the radiofrequency pulses. Herein, we extend alternating balanced steady state imaging to multiple balanced alternating steady states for estimation of neural current waveforms. Simulations and phantom experiments show that the off-resonance profile of the multiple alternating steady state signal carries information about the frequency content of driving waveforms. In addition, the method is less sensitive than alternating balanced steady state to precise waveform timing relative to radiofrequency pulses. Thus, multiple alternating steady state technique is potentially applicable to MR imaging of the waveforms of periodic neuronal activity.

Modulation of neuronal responses during covert search for visual feature conjunctions.

While searching for an object in a visual scene, an observer's attentional focus and eye movements are often guided by information about object features and spatial locations. Both spatial and feature-specific attention are known to modulate neuronal responses in visual cortex, but little is known of the dynamics and interplay of these mechanisms as visual search progresses. To address this issue, we recorded from directionally selective cells in visual area MT of monkeys trained to covertly search for targets defined by a unique conjunction of color and motion features and to signal target detection with an eye movement to the putative target. Two patterns of response modulation were observed. One pattern consisted of enhanced responses to targets presented in the receptive field (RF). These modulations occurred at the end-stage of search and were more potent during correct target identification than during erroneous saccades to a distractor in RF, thus suggesting that this modulation is not a mere presaccadic enhancement. A second pattern of modulation was observed when RF stimuli were nontargets that shared a feature with the target. The latter effect was observed during early stages of search and is consistent with a global feature-specific mechanism. This effect often terminated before target identification, thus suggesting that it interacts with spatial attention. This modulation was exhibited not only for motion but also for color cue, although MT neurons are known to be insensitive to color. Such cue-invariant attentional effects may contribute to a feature binding mechanism acting across visual dimensions.

The effect of spatial attention on contrast response functions in human visual cortex.

Previous electrophysiology data suggests that the modulation of neuronal firing by spatial attention depends on stimulus contrast, which has been described using either a multiplicative gain or a contrast-gain model. Here we measured the effect of spatial attention on contrast responses in humans using functional MRI. To our surprise, we found that the modulation of blood oxygenation level-dependent (BOLD) responses by spatial attention does not greatly depend on stimulus contrast in visual cortical areas tested [V1, V2, V3, and MT+ (middle temporal area)]. An additive model, rather than a multiplicative or contrast-gain model best describes the attentional modulations in V1. This inconsistency with previous single-unit electrophysiological data has implications for the population-based neuronal source of the BOLD signal.

Global effects of feature-based attention in human visual cortex.

The content of visual experience depends on how selective attention is distributed in the visual field. We used functional magnetic resonance imaging (fMRI) in humans to test whether feature-based attention can globally influence visual cortical responses to stimuli outside the attended location. Attention to a stimulus feature (color or direction of motion) increased the response of cortical visual areas to a spatially distant, ignored stimulus that shared the same feature.

The relationship between task performance and functional magnetic resonance imaging response.

We compared psychophysical and functional magnetic resonance imaging (fMRI) responses within areas V1-V3 and MT+ during both a speed and a contrast discrimination task. We found that fMRI responses did not depend significantly on task in any of these areas. Moreover, responses in V1-V3 were larger than those in MT+ for both the speed and the contrast discrimination tasks across a wide range of contrasts. This pattern of results demonstrates that localizing function based on finding those regions of cortex that show greater activity to a given task-stimulus combination than to other tasks and stimuli may, under certain conditions, be misleading. However, a simple ideal observer model assuming that perceptual thresholds are dependent on neuronal population responses does successfully show that V1 has neuronal properties consistent with our subjects' contrast discrimination performance, and that MT+ has neuronal properties consistent with subjects' performance on a speed discrimination task.

Global feature-based attention for motion and color.

We used a divided attention psychophysical task to test the hypothesis that visual attention to a stimulus feature(1) facilitates the processing of other stimuli sharing the same feature. Performance on a dual-task was significantly better when human observers divided attention across two spatially separate stimuli sharing a common feature (same direction of motion or same color) compared to opposing features. This attentional effect was dependent upon the presence of competing stimuli. These results are consistent with a spatially global feature-based mechanism of attention that increases the response of cortical neurons tuned to an attended feature throughout the visual field.

Imaging periodic currents using alternating balanced steady-state free precession.

Existing functional brain MR imaging methods detect neuronal activity only indirectly via a surrogate signal such as deoxyhemoglobin concentration in the vascular bed of cerebral parenchyma. It has been recently proposed that neuronal currents may be measurable directly using MRI (ncMRI). However, limited success has been reported in neuronal current detection studies that used standard gradient or spin echo pulse sequences. The balanced steady-state free precession (bSSFP) pulse sequence is unique in that it can afford the highest known SNR efficiency and is exquisitely sensitive to perturbations in free precession phase. It is reported herein that when a spin phase-perturbing periodic current is locked to an RF pulse train, phase perturbations are accumulated across multiple RF excitations and the spin magnetization reaches an alternating balanced steady state (ABSS) that effectively amplifies the phase perturbations due to the current. The alternation of the ABSS signal therefore is highly sensitive to weak periodic currents. Current phantom experiments employing ABSS imaging resulted in detection of magnetic field variations as small as 0.15nT in scans lasting for 36 sec, which is more sensitive than using gradient-recalled echo imaging.

Spatial and cross-modal attention alter responses to unattended sensory information in early visual and auditory human cortex.

Attending to a visual or auditory stimulus often requires irrelevant information to be filtered out, both within the modality attended and in other modalities. For example, attentively listening to a phone conversation can diminish our ability to detect visual events. We used functional magnetic resonance imaging (fMRI) to examine brain responses to visual and auditory stimuli while subjects attended visual or auditory information. Although early cortical areas are traditionally considered unimodal, we found that brain responses to the same ignored information depended on the modality attended. In early visual area V1, responses to ignored visual stimuli were weaker when attending to another visual stimulus, compared with attending to an auditory stimulus. The opposite was true in more central visual area MT+, where responses to ignored visual stimuli were weaker when attending to an auditory stimulus. Furthermore, fMRI responses to the same ignored visual information depended on the location of the auditory stimulus, with stronger responses when the attended auditory stimulus shared the same side of space as the ignored visual stimulus. In early auditory cortex, responses to ignored auditory stimuli were weaker when attending a visual stimulus. A simple parameterization of our data can describe the effects of redirecting attention across space within the same modality (spatial attention) or across modalities (cross-modal attention), and the influence of spatial attention across modalities (cross-modal spatial attention). Our results suggest that the representation of unattended information depends on whether attention is directed to another stimulus in the same modality or the same region of space.

Efficient design of event-related fMRI experiments using M-sequences.

Rapid event-related fMRI (erfMRI) allows estimation of the shape of hemodynamic responses (HDR) associated with transient brain activation evoked by various sensory, motor, and cognitive events. Choosing a sequence of events that maximizes efficiency of estimating the HDR is essential for conducting event-related brain imaging experiments, since increasing efficiency is essentially equivalent to reducing scanning time or increasing the strength of the principal magnetic field. The efficiency of an erfMRI design depends critically on the temporal arrangement of the sequence of events and the noise in the fMRI signal. We introduce to erfMRI a simple method for generating efficient event sequences based on maximum-length shift register sequences, or m-sequences. We show that under the assumption of white uncorrelated MRI noise, efficiency of erfMRI experimental designs that employ m-sequences exceeds efficiency of the best randomly generated sequences. This is true for single and multiple event type experiments, which allow either parallel events (overlapping events design) or designs in which only one event occurs at a time (nonoverlapping events design). HDR estimation efficiency afforded by m-sequences grows with the number of event types, and is greatest when event sequences are relatively short, albeit within commonly used scan times (i.e., 63-255 total events per scan). The improvement in efficiency, however, comes at a cost of constraints imposed by m-sequence generation rules, such as predetermined sequence lengths; for nonoverlapping events design m-sequence-based designs are not available for all possible numbers of event types. Nevertheless, designs that are available with m-sequences cover a large subset of commonly used erfMRI experimental designs. Under conditions of characteristic time-correlated fMRI noise, randomly generated sequences may yield efficiencies that exceed those afforded by m-sequences for single event-type designs, since in this case one can generate random sequences that partially decorrelate MRI noise by chance. Our simulations suggest that for designs of realistic sequence lengths that use more than one event type, m-sequence based designs tend to outperform random designs, thus making the knowledge of noise inessential. Finally, within an r-th order m-sequence (generated by a shift register of length r) all possible combinations of subsequences of length r occur, and thus these subsequences are exactly counterbalanced. This property is essential for minimizing effects of psychological and neuronal adaptation and expectation.

Caffeine alters the temporal dynamics of the visual BOLD response.

The blood oxygenation level-dependent (BOLD) responses to visual stimuli, using both a 1-s long single trial stimulus and a 20-s long block stimulus, were measured in a 4-T magnetic field both before and immediately after a 200-mg caffeine dose. In addition, resting levels of cerebral blood flow (CBF) were measured using arterial spin labeling. For the single trial stimulus, the caffeine dose significantly (p<0.05) reduced the time to peak (TTP), the time after the peak at which the response returned to 50% of the peak amplitude (TA50), and the amplitude of the poststimulus undershoot in all subjects (N=5). Other parameters, such as the full-width half-maximum (FWHM) and the peak amplitude, also showed significant changes in the majority of subjects. For the block stimulus, the TTP, TA50, and the time for the response to reach 50% of the peak amplitude (T50) were significantly reduced. In some subjects, oscillations were observed in the poststimulus portion of the response with median peak periods of 9.1 and 9.5 s for the single trial and block responses, respectively. Resting CBF was reduced by an average of 24%. The reproducibility of the results was verified in one subject who was scanned on 3 different days. The dynamic changes are similar to those previously reported for baseline CBF reductions induced by hypocapnia and hyperoxia.