Richard Bowtell

''Sparse'' Temporal Sampling in Auditory fMRI

The use of functional magnetic resonance imaging (fMRI) to explore central auditory function may be compromised by the intense bursts of stray acoustic noise produced by the scanner whenever the magnetic resonance signal is read out. We present results evaluating the use of one method to reduce the effect of the scanner noise: “sparse” temporal sampling. Using this technique, single volumes of brain images are acquired at the end of stimulus and baseline conditions. To optimize detection of the activation, images are taken near to the maxima and minima of the hemodynamic response during the experimental cycle. Thus, the effective auditory stimulus for the activation is not masked by the scanner noise.

Representation of Pleasant and Aversive Taste in the Human Brain

In this study, the representation of taste in the orbitofrontal cortex was investigated to determine whether or not a pleasant and an aversive taste have distinct or overlapping representations in this region. The pleasant stimulus used was sweet taste (1 M glucose), and the unpleasant stimulus was salt taste (0.1 M NaCl). We used an ON/OFF block design in a 3T fMRI scanner with a tasteless solution delivered in the OFF period to control for somatosensory or swallowing-related effects. It was found that parts of the orbitofrontal cortex were activated (P < 0.005 corrected) by glucose (in 6/7 subjects) and by salt (in 6/7 subjects). In the group analysis, separate areas of the orbitofrontal cortex were found to be activated by pleasant and aversive tastes. The involvement of the amygdala in the representation of pleasant as well as aversive tastes was also investigated. The amygdala was activated (region of interest analysis, P < 0.025 corrected) by the pleasant taste of glucose (5/7 subjects) as well as by the aversive taste of salt (4/7 subjects). Activation by both stimuli was also found in the frontal opercular/insular (primary) taste cortex. We conclude that the orbitofrontal cortex is involved in processing tastes that have both positive and negative affective valence and that different areas of the orbitofrontal cortex may be activated by pleasant and unpleasant tastes. We also conclude that the amygdala is activated not only by an affectively unpleasant taste, but also by a taste that is affectively pleasant, thus providing evidence that the amygdala is involved in effects produced by positively affective as well as by negatively affective stimuli.

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p <0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p <0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas.

Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.

fMRI of the Responses to Vibratory Stimulation of Digit Tips

Three studies were carried out to assess the applicability of fMRI at 3.0 T to analysis of vibrotaction in humans. A novel piezoelectric device provided clean sinusoidal stimulation at 80 Hz, which was initially applied in separate runs within a scanning session to digits 2 and 5 of the left hand in eight subjects, using a birdcage RF (volume) coil. Significant clusters of activation were found in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), subcentral gyrus, the precentral gyrus, posterior insula, posterior parietal regions (area 5), and the posterior cingulate. Digit separation in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study carried out in six additional subjects using a surface coil, replicated the main contralateral activation patterns detected in study one and further improved the discrimination of the digits in SI. Significant digit separation was also found in SII and in the posterior insula. A third study to investigate the frequency dependence of the response focused on the effect of an increase in vibrotactile frequency from 30 to 80 Hz, with both frequencies applied to digit 2 during the same scanning session in four new subjects. A significant increase in the number of pixels activated within both SII and the posterior insula was found, while the number of pixels activated in SI declined. No significant change in signal intensity with frequencies was found in any of the activated areas.

Multiple spin echoes in liquids in a high magnetic field

We have observed multiple spin echoes using an NMR microscopy system which has a field of 11.7 T. Our experimental results show that the cause of the MSE is the dipolar demagnetizing field. This is also the origin of MSE seen in solid 3 He and in liquid 3 He at low temperatures

Susceptibility mapping in the human brain using threshold-based k-space division

A method for calculating quantitative three‐dimensional susceptibility maps from field measurements acquired using gradient echo imaging at high field is presented. This method is based on division of the three‐dimensional Fourier transforms of high‐pass‐filtered field maps by a simple function that is the Fourier transform of the convolution kernel linking field and susceptibility, and uses k‐space masking to avoid noise enhancement in regions where this function is small. Simulations were used to show that the method can be applied to data acquired from objects that are oriented at one angle or multiple angles with respect to the applied field and that the use of multiple orientations improves the quality of the calculated susceptibility maps. As part of this work, we developed an improved approach for high‐pass filtering of field maps, based on using an arrangement of dipoles to model the fields generated by external structures. This approach was tested on simulated field maps from the substantia nigra and red nuclei. Susceptibility mapping was successfully applied to experimental measurements on a structured phantom and then used to make measurements of the susceptibility of the red nuclei and substantia nigra in healthy subjects at 3 and 7 T. Magn Reson Med 63:1292–1304, 2010.

Whole-brain susceptibility mapping at high field: a comparison of multiple- and single-orientation methods.

Optimisation and comparison of the performance of three different methods for calculating three-dimensional susceptibility maps of the whole brain from gradient-echo (phase and modulus) image data acquired at 7 T is described. The methods studied are a multiple-orientation method in which image data acquired with the head at several different angles to the main field are combined and two methods which use data acquired at a single orientation: the first of these is based on exclusion of some k-space data from the calculation (through thresholding of the dipolar field kernel), while the second incorporates a regularisation method that is based on using information from the modulus images. The methods were initially optimised via analysis of data from a phantom containing different compartments of known susceptibility. As part of this work, a novel high-pass filtering methodology was introduced to remove background fields from field maps based on phase data. The optimised methods were successfully applied to high-resolution (0.7 mm isotropic) whole-brain modulus and phase data acquired in vivo from five healthy male subjects, 25-30 years of age. The multiple-orientation method yielded high quality susceptibility maps, out-performing the single-orientation methods. Venous blood vessels as well as the substantia nigra and globus pallidus brain regions showed particularly high positive susceptibility offsets relative to surrounding tissue, consistent with high deoxyhemoglobin and non-heme iron content, respectively. To compare the performance of the different methods, regions of interest were drawn in deep grey matter structures and in cortical grey and white matter. The threshold-based approach was fast and simple to use, but underestimated susceptibility differences and showed significant artefacts due to noise amplification in difficult regions of k-space. The regularised single-orientation method yielded contrast dependent on the choice of spatial priors, but demonstrated the potential to yield susceptibility maps of a similar quality to those calculated using data acquired at multiple orientations to the field.

Fiber orientation-dependent white matter contrast in gradient echo MRI

Recent studies have shown that there is a direct link between the orientation of the nerve fibers in white matter (WM) and the contrast observed in magnitude and phase images acquired using gradient echo MRI. Understanding the origin of this link is of great interest because it could offer access to a new diagnostic tool for investigating tissue microstructure. Since it has been suggested that myelin is the dominant source of this contrast, creating an accurate model for characterizing the effect of the myelin sheath on the evolution of the NMR signal is an essential step toward fully understanding WM contrast. In this study, we show by comparison of the results of simulations and experiments carried out on human subjects at 7T, that the magnitude and phase of signals acquired from WM in vivo can be accurately characterized by (i) modeling the myelin sheath as a hollow cylinder composed of material having an anisotropic magnetic susceptibility that is described by a tensor with a radially oriented principal axis, and (ii) adopting a two-pool model in which the water in the sheath has a reduced T2 relaxation time and spin density relative to its surroundings, and also undergoes exchange. The accuracy and intrinsic simplicity of the hollow cylinder model provides a versatile framework for future exploitation of the effect of WM microstructure on gradient echo contrast in clinical MRI.

fMRI at 1.5, 3 and 7 T: characterising BOLD signal changes

Blood oxygenation level dependent (BOLD) signal changes occurring during execution of a simple motor task were measured at field strengths of 1.5, 3 and 7 T using multi-slice, single-shot, gradient echo EPI at a resolution of 1x1x3 mm(3), to quantify the benefits offered by ultra-high magnetic field for functional MRI. Using four different echo times at each field strength allowed quantification of the relaxation rate, R(2)* and the change in relaxation rate on activation, DeltaR(2)*. This work adds to previous studies of the field strength dependence of BOLD signal characteristics, through its: (i) focus on motor rather than visual cortex; (ii) use of single-shot, multi-slice, gradient echo EPI for data acquisition; (iii) co-registration of images acquired at different field strengths to allow assessment of the BOLD signal changes in the same region at each field strength. DeltaR(2)* was found to increase linearly with field strength (0.51+/-0.06 s(-1) at 1.5 T; 0.98+/-0.08 s(-1) at 3 T; 2.55+/-0.22 s(-1) at 7 T), while the ratio of DeltaR(2)*/R(2), which dictates the accessible BOLD contrast was also found to increase (0.042+/-0.002 at 1.5 T; 0.054+/-0.002 at 3 T; 0.084+/-0.003 at 7 T). The number of pixels classified as active, the t-value calculated over a common region of interest and the percentage signal change in the same region were all found to peak at TE approximately T(2)* and increase significantly with field strength. An earlier onset of the haemodynamic response at higher field provides some evidence for a reduced venous contribution to the BOLD signal at 7 T.