Investigations on spinal cord fMRI of cats under ketamine.

Functional magnetic resonance imaging (fMRI) of the spinal cord has been the subject of intense research for the last ten years. An important motivation for this technique is its ability to detect non-invasively neuronal activity in the spinal cord related to sensorimotor functions in various conditions, such as after spinal cord lesions. Although promising results of spinal cord fMRI have arisen from previous studies, the poor reproducibility of BOLD activations and their characteristics remain a major drawback. In the present study we investigated the reproducibility of BOLD fMRI in the spinal cord of cats (N=9) by repeating the same stimulation protocol over a long period (approximately 2 h). Cats were anaesthetized with ketamine, and spinal cord activity was induced by electrical stimulation of cutaneous nerves of the hind limbs. As a result, task-related signals were detected in most cats with relatively good spatial specificity. However, BOLD response significantly varied within and between cats. This variability was notably attributed to the moderate intensity of the stimulus producing a low amplitude haemodynamic response, variation in end-tidal CO(2) during the session, low signal-to-noise ratio (SNR) in spinal fMRI time series and animal-specific vascular anatomy. Original contributions of the present study are: (i) first spinal fMRI experiment in ketamine-anaesthetized animals, (ii) extensive study of intra- and inter-subject variability of activation, (iii) characterisation of static and temporal SNR in the spinal cord and (iv) investigation on the impact of CO(2) end-tidal level on the amplitude of BOLD response.

Conflict monitoring in the human anterior cingulate cortex during selective attention to global and local object features.

Parallel processing affords the brain many advantages, but processing multiple bits of information simultaneously presents formidable challenges. For example, while one is listening to a speaker at a noisy social gathering, processing irrelevant conversations may lead to the activation of irrelevant perceptual, semantic, and response representations that conflict with those evoked by the speaker. In these situations, specialized brain systems may be recruited to detect and resolve conflict before it leads to incorrect perception and/or behavior. Consistent with this view, recent findings indicate that dorsal/caudal anterior cingulate cortex (dACC), on the medial walls of the frontal lobes, detects conflict between competing motor responses primed by relevant versus irrelevant stimuli. Here, we used a cued global/local selective attention task to investigate whether the dACC plays a general role in conflict detection that includes monitoring for conflicting perceptual or semantic representations. Using event-related functional magnetic resonance imaging (fMRI), we found that the dACC was activated by response conflict in both the global and the local task, consistent with results from prior studies. However, dACC was also activated by perceptual and semantic conflict arising from global distracters during the local task. The results from the local task have implications for recent theories of attentional control in which the dACC's contribution to conflict monitoring is limited to response stages of processing, as well as for our understanding of clinical disorders in which disruptions of attention are associated with dACC dysfunction.

Neural mechanisms of top-down control during spatial and feature attention.

Theories of visual selective attention posit that both spatial location and nonspatial stimulus features (e.g., color) are elementary dimensions on which top-down attentional control mechanisms can selectively influence visual processing. Neuropsychological and neuroimaging studies have demonstrated that regions of superior frontal and parietal cortex are critically involved in the control of visual-spatial attention. This frontoparietal control network has also been found to be activated when attention is oriented to nonspatial stimulus features (e.g., motion). To test the generality of the frontoparietal network in attentional control, we directly compared spatial and nonspatial attention in a cuing paradigm. Event-related fMRI methods permitted the isolation of attentional control activity during orienting to a location or to a nonspatial stimulus feature (color). Portions of the frontoparietal network were commonly activated to the spatial and nonspatial cues. However, direct statistical comparisons of cue-related activity revealed subregions of the frontoparietal network that were significantly more active during spatial than nonspatial orienting when all other stimulus, task, and attentional factors were equated. No regions of the frontal-parietal network were more active for nonspatial cues in comparison to spatial cues. These findings support models suggesting that subregions of the frontal-parietal network are highly specific for controlling spatial selective attention.

Lorentz effect imaging.

This paper presents a method that can detect minute electrical activity in a strong magnetic field. It uses displacement encoding to detect small spatial displacement induced by Lorentz force on the conducting materials, hence the term Lorentz effect imaging (LEI). With increased sensitivity from improved hardware capabilities or signal averaging, this technique may be used to detect spatial displacements induced by small currents comparable to neuronal electrical current. The initial results using the LEI technique may provide insight in assessing the feasibility of using MRI to non-invasively detect the neuronal electrical activities.

Single-shot EPI with signal recovery from the susceptibility-induced losses.

A major problem in the gradient-recalled echo-planar imaging (EPI) method that also uses a long echo time (TE) is the severe signal loss in regions with large static field inhomogeneities. These regions include the ventral frontal, medial temporal, and inferior temporal lobes, which experience inhomogeneities induced by susceptibility effects commonly found near air/tissue interfaces. For functional magnetic resonance imaging (fMRI) studies that use both gradient-recalled EPI at relatively long TE and high-field scanners, this signal loss is severe, preventing investigation of certain human cognitive processes that involve these regions, such as memory and attention. Methods have been developed to recover this signal loss; however, most of them require multiple excitations and thus compromise temporal resolution. In this report, a new technique is described which achieves good signal recovery within a single excitation. It is anticipated that this technique will prove useful for fMRI studies in inhomogeneous areas that require high temporal resolution.

Linking sight and sound: fMRI evidence of primary auditory cortex activation during visual word recognition.

We describe two studies that used repetition priming paradigms to investigate brain activity during the reading of single words. Functional magnetic resonance images were collected during a visual lexical decision task in which nonword stimuli were manipulated with regard to phonological properties and compared to genuine English words. We observed a region in left-hemisphere primary auditory cortex linked to a repetition priming effect. The priming effect activity was observed only for stimuli that sound like known words; moreover, this region was sensitive to strategic task differences. Thus, a brain region involved in the most basic aspects of auditory processing appears to be engaged in reading even when there is no environmental oral or auditory component.

Segmented spin-echo pulses to increase fMRI signal: repeated intrinsic diffusional enhancement.

Since its inception, functional magnetic resonance imaging (fMRI) has seen rapid progress in the application to neuroscience. Common gradient-recalled acquisition methods are susceptible to static field inhomogeneities, resulting in signal loss at the medial temporal area important for memory function or at the basal ganglia area for motor control. In addition, they are susceptible to the contaminating signals of large vein origin, such as the signals from its surrounding cerebrospinal fluid (CSF) leading to false-positive activation. Spin echoes overcome these drawbacks. However, they are less sensitive to blood oxygenation level dependent (BOLD) susceptibility changes because of their refocusing mechanism. A method is presented here to enhance the spin-echo fMRI signal by recruiting more spins to participate in the dynamic BOLD process. This method divided a conventional T(2) weighting period into several segments separated by blocks of extra free diffusion time. Before the extra diffusion time spins are restored to the longitudinal axis preventing rapid transverse relaxation. This process allows more spin access to the regions that experience the BOLD field gradient. Because of the increased spin population that is modulated by the capillary BOLD field gradient, the functional signal is increased. Spin-echo echo-planar imaging (EPI) with this enhancement may be a useful technique for fMRI studies at inhomogeneous areas such as the air/tissue interface. Magn Reson Med 42:631-635, 1999.

A confrontational naming task produces congruent increases and decreases in PET and fMRI.

This work uses the well-established (by PET) confrontation naming task to compare PET and fMRI in a cognitive activation experiment. The signal changes from this task are much less than the changes caused by visual or motor activation tasks used in previous comparisons. ANOVA methods adjusted for multiple comparisons were used to determine significant changes in signal between confrontation naming and figure size discrimination tasks. All 17 significantly increased regions (confrontation naming signal greater) seen on one modality were increased on both modalities. Ten of 13 regions that were significantly decreased on one modality were decreased on the other. Three mismatched regions showed a significant decrease on one modality and a nonsignificant increase on the other. This study could not detect a consistent difference in activation site location between PET and fMRI.

Continuous functional magnetic resonance imaging reveals dynamic nonlinearities of "dose-response" curves for finger opposition.

Linear experimental designs have dominated the field of functional neuroimaging, but although successful at mapping regions of relative brain activation, the technique assumes that both cognition and brain activation are linear processes. To test these assumptions, we performed a continuous functional magnetic resonance imaging (MRI) experiment of finger opposition. Subjects performed a visually paced bimanual finger-tapping task. The frequency of finger tapping was continuously varied between 1 and 5 Hz, without any rest blocks. After continuous acquisition of fMRI images, the task-related brain regions were identified with independent components analysis (ICA). When the time courses of the task-related components were plotted against tapping frequency, nonlinear "dose- response" curves were obtained for most subjects. Nonlinearities appeared in both the static and dynamic sense, with hysteresis being prominent in several subjects. The ICA decomposition also demonstrated the spatial dynamics with different components active at different times. These results suggest that the brain response to tapping frequency does not scale linearly, and that it is history-dependent even after accounting for the hemodynamic response function. This implies that finger tapping, as measured with fMRI, is a nonstationary process. When analyzed with a conventional general linear model, a strong correlation to tapping frequency was identified, but the spatiotemporal dynamics were not apparent.

T1-selective diffusion weighted fMRI at 1.5T.

Apparent diffusion coefficients (ADC) of protons contributing to the functional signal can be determined from diffusion weighted functional magnetic resonance imaging (MRI) studies. An earlier study indicated that ADCs calculated from the functional signal of an activated primary sensorimotor cortex are large, and consistent with a CSF or intravascular contribution to the functional signal. We have added inversion recovery pulses to isotropic diffusion weighted imaging to null CSF protons selectively within the imaging slice, or to null the outer volume blood flowing into the imaging slice. With the use of gradient recalled diffusion weighted echo-planar imaging at low gradient b factors, and without the use of inversion pulses, the ADCs x 10(3) in mm2/s (+/- SD) from the functional signal were 6.81 +/- 1.19. These ADCs were significantly higher than resting primary sensorimotor cortex ADCs of 2.26 +/- 1.49, measured at the same b factors. When CSF nulling was applied, the functional signal ADCs remained high. Application of inflow nulling decreased the functional signal to such a small value, that ADCs estimated from these functional signals were not assessed. The results are consistent with an intravascular contribution to the functional signal and to its large ADC.

The effect of off-resonance radiofrequency pulse saturation on fMRI contrast.

This paper describes the use of off-resonance saturation to further manipulate the blood oxygenation level dependent (BOLD) contrast of fMRI. A customized narrow bandwidth radiofrequency pulse, applied with a range of frequency offsets prior to selection of each slice, was designed and incorporated into a gradient echo EPI sequence. This application takes advantage of the resonance frequency and linewidth differences between the oxygenated and deoxygenated state of blood in human brain during task activation and rest, and is capable of creating an enhancement in the contrast of the BOLD effect. Because of a possible contribution to the signal change from cerebro-spinal fluid, which has a much narrower linewidth and smaller frequency shift compared with the brain tissue, data were also collected using a nulling inversion pulse. The inversion pulse was applied before the off-resonance pulse and data acquisition to eliminate the CSF signal. Functional areas are thus more localized to the brain tissue.

Technical foundations and pitfalls of clinical fMRI.

Magnetic resonance imaging (MRI) has become an established and invaluable tool in the diagnosis of numerous diseases through its ability to show pathologic contrast in images of soft tissue. More recently, MRI has found application in the study of organ function, principally in the brain and heart. This article deals with MRI imaging of brain function and describes some of the techniques that allow physiological parameters such as cerebral blood volume, cerebral blood oxygenation, and cerebral perfusion to be determined. Additionally, some of the potentially confounding influences in these experiments are discussed.

Diffusion weighted fMRI at 1.5 T.

Functional magnetic resonance imaging (fMRI) is capable of detecting task-induced blood oxygenation changes using susceptibility sensitive pulse sequences such as gradient-recalled echo-planar imaging (EPI). The local signal increases seen in the time course are believed to be due to an increase in oxygen delivery that is incommensurate with oxygen demands. To help isolate the sources of functional signal changes, the authors have incorporated various forms of diffusion weighting into EPI pulse sequences to characterize the apparent mobility of the functionally modulated protons. Results suggest that the majority of the functional signal at 1.5 T arises from protons that have apparent diffusion coefficients that are approximately four or five times higher than that of brain tissue. This implies that significant functional signal sources are either protons within the vascular space or protons from the perivascular space that is occupied by cerebrospinal fluid.

Optimized isotropic diffusion weighting.

The authors introduce several sets of time-efficient gradient waveforms for applying isotropic diffusion weighting in NMR experiments. This creates signal attenuation that depends on the trace of the diffusion tensor and is therefore rotationally invariant. Numerical methods for the calculation of such gradient sets are outlined, and results are shown for isotropic and anisotropic gradient hardware and first order flow moment nulled diffusion weighting gradients. Preliminary experimental results from the human brain validate this new technique.

Echo-volume imaging.

Two single-shot volume imaging techniques are described. The first, single-echo echo-volume imaging, is essentially the echo-volume imaging (EVI) sequence suggested by Mansfield (J. Phys. C. 10, L55 (1977)). The second is a multi-spin-echo approach in which one plane of k-space is collected during each spin echo. In both techniques, phase encoding gradients are applied in the z direction, and three-dimensional k-space is filled by a raster pattern in Cartesian coordinates. Spatial saturation is used to avoid aliasing in the y direction, and a selctive pulse is applied to excite the desired slab of tissue and eliminate aliasing in z. The average echo-times, measured from the center of the 90 degrees pulse to the center of the acquisition k-space (kx = ky = kz = 0), were 45 and 104 ms for single echo and multi-echo methods, respectively. Images of the human brain using both sequences are shown.