Peter Jezzard

Thalamic neurodegeneration in multiple sclerosis.

Multiple sclerosis is still regarded primarily as a disease of the white matter. However, recent evidence suggests that there may be significant involvement of gray matter. Here, we have used magnetic resonance imaging and magnetic resonance spectroscopy in vivo and histopathology postmortem to estimate thalamic neuronal loss in patients with multiple sclerosis. Our results show that neuronal loss in multiple sclerosis can be substantial (30–35% reduction). We conclude that a neurodegenerative pathology may make a major contribution to the genesis of symptoms in multiple sclerosis.

Activation of Prefrontal Cortex in Children during a Nonspatial Working Memory Task with Functional MRI

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of activity of prefrontal cortex in prepubertal children during performance of a nonspatial working memory task. The children observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Location of activation closely approximated that observed in a recent fMRI study with adults using exactly the same task. Activation of the inferior and middle frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Activation increased and decreased with a time course that was highly consistent with the task manipulations and correlated with behavioral performance. To our knowledge, this study is one of the first to demonstrate the applicability of fMRI to a normative developmental population. Issues of age dependence of the hemodynamic responses of fMRI are discussed.

Sources of distortion in functional MRI data.

Functional magnetic resonance image (fMRI) experiments rely on the ability to detect subtle signal changes in magnetic resonance image time series. Any areas of signal change that correlate with the neurological stimulus can then be identified and compared with a corresponding high‐resolution anatomical scan. This report reviews some of the several artefacts that are frequently present in fMRI data, degrading their quality and hence their interpretation. In particular, the effects of magnetic field inhomogeneities are described, both on echo planar imaging (EPI) data and on spiral imaging data. The modulation of these distortions as the subject moves in the magnet is described. The effects of gradient coil nonlinearities and EPI ghost correction schemes are also discussed. Hum. Brain Mapping 8:80–85, 1999.

Reduction in Occipital Cortex γ-Aminobutyric Acid Concentrations in Medication-Free Recovered Unipolar Depressed and Bipolar Subjects

BACKGROUND Studies using proton magnetic resonance spectroscopy (MRS) have indicated that unmedicated, acutely depressed patients have decreased levels of gamma-aminobutyric acid (GABA) in occipital cortex. Cortical levels of glutamate (Glu) may be increased, although these data are less consistent. The aim of this study was to use MRS to determine whether changes in GABA and Glu levels were present in patients with mood disorders who had recovered and were no longer taking medication. METHODS An [1H]-MRS was used to measure levels of GABA, of the combined concentration of Glu and glutamine (Gln), and of N-acetylaspartate (NAA) in occipital cortex in medication-free, fully recovered subjects with a history of recurrent unipolar depression (n = 15), bipolar disorder (n = 16), and a group of healthy controls (n = 18). RESULTS Occipital levels of GABA and NAA were significantly lower in recovered depressed and bipolar subjects than in healthy controls, whereas Glu +Gln concentrations were higher. CONCLUSIONS Our data suggest that recovered unmedicated subjects with a history of mood disorder have changes in cortical concentrations of GABA, NAA, and Glu +Gln. These biochemical abnormalities may be markers of a trait vulnerability to mood disorder, rather than neurochemical correlates of an abnormal mood state.

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy.

Continuous theta burst stimulation (cTBS) is a novel transcranial stimulation technique that causes significant inhibition of synaptic transmission for ≤1 h when applied over the primary motor cortex (M1) in humans. Here we use magnetic resonance spectroscopy to define mechanisms mediating this inhibition by noninvasively measuring local changes in the cortical concentrations of γ-aminobutyric acid (GABA) and glutamate/glutamine (Glx). cTBS to the left M1 led to an increase in GABA compared with stimulation at a control site without significant change in Glx. This direct evidence for increased GABAergic interneuronal activity is framed in terms of a new hypothesis regarding mechanisms underlying cTBS.

Thalamic neurodegeneration in relapsing-remitting multiple sclerosis

Objective: To define the extent of neuronal injury and loss in thalamic gray matter in patients with relapsing-remitting (RR) MS and to characterize how these neuronal pathologic changes are related to disease duration. Methods: The authors studied 14 patients with RRMS (Expanded Disability Status Scale score, mean 3.25, range 2.0 to 6.0) and 14 (8 men, 6 women) age-matched healthy controls. Structural MR and MRS studies were performed in a single scanning session using a 3T MR system. Results: N-acetylaspartate (NAA) concentrations (a measure of the apparent neuronal density) were decreased approximately 11% in the thalami of the patients with RRMS relative to controls (p < 0.05). The patients with RRMS also had an almost 25% lower mean normalized thalamic volume than controls (p < 0.005). Decreases in thalamic NAA concentration correlated strongly with thalamic volume loss for individual patients (r = 0.85, p < 0.01). Both the NAA concentration (r = −0.48, p = 0.044) and normalized thalamic volume (r = −0.60, p = 0.01) were correlated inversely with disease duration. There was a trend for a correlation between the thalamic NAA/creatine (Cr) ratio and the NAA/Cr in the frontal normal-appearing white matter (r = 0.56, p < 0.08). Conclusions: The reduction of both NAA concentration and thalamic volume suggests that a neurodegenerative component may contribute to the pathology of MS even in the earlier RR stage. The trend toward a relationship between thalamic NAA/Cr and distant normal-appearing white matter changes implies that there may be a common mechanism for the white matter axonal loss and thalamic neuronal injury.

Sentence reading: A functional mri study at 4 tesla

In this study, changes in blood oxygenation and volume were monitored while monolingual right-handed subjects read English sentences. Our results confirm the role of the left peri-sylvian cortex in language processing. Interestingly, individual subject analyses reveal a pattern of activation characterized by several small, limited patches rather than a few large, anatomically well-circumscribed centers. Between-subject analyses confirm a lateralized pattern of activation and reveal active classical language areas including Brocas area, Wernickes area, and the angular gyms. In addition they point to areas only more recently considered as language-relevant including the anterior portion of the superior temporal sulcus. This area has not been reliably observed in imaging studies of isolated word processing. This raises the hypothesis that activation in this area is dependent on processes specific to sentence reading.

A calibration method for quantitative BOLD fMRI based on hyperoxia

The estimation of changes in CMR(O2) using functional MRI involves an essential calibration step using a vasoactive agent to induce an isometabolic change in CBF. This calibration procedure is performed most commonly using hypercapnia as the isometabolic stimulus. However, hypercapnia possesses a number of detrimental side effects. Here, a new method is presented using hyperoxia to perform the same calibration step. This procedure requires independent measurement of Pa(O2), the BOLD signal, and CBF. We demonstrate that this method yields results that are comparable to those derived using other methods. Further, the hyperoxia technique is able to provide an estimate of the calibration constant that has lower overall intersubject and intersession variability compared to the hypercapnia approach.

Cerebral perfusion response to hyperoxia.

Graded levels of supplemental inspired oxygen were investigated for their viability as a noninvasive method of obtaining intravascular magnetic resonance image contrast. Administered hyperoxia has been shown to be effective as a blood oxygenation level-dependent contrast agent for magnetic resonance imaging (MRI); however, it is known that high levels of inspired fraction of oxygen result in regionally decreased perfusion in the brain potentially confounding the possibility of using hyperoxia as a means of measuring blood flow and volume. Although the effects of hypoxia on blood flow have been extensively studied, the hyperoxic regime between normoxia and 100% inspired oxygen has been only intermittently studied. Subjects were studied at four levels of hyperoxia induced during a single session while perfusion was measured using arterial spin labelling MRI. Reductions in regional perfusion of grey matter were found to occur even at moderate levels of hyperoxia; however, perfusion changes at all oxygen levels were relatively mild (less than 10%) supporting the viability of hyperoxia-induced contrast.

Fast, fully automated global and local magnetic field optimization for fMRI of the human brain.

The aim of this novel technique is to allow researchers, particularly those operating at high static magnetic field strengths on fMRI applications, to tailor the static magnetic field within the brain. The optimum solution for their experimental needs is reached, utilizing the full potential of the active shims at their disposal. The method for shimming human brain, which incorporates automatic brain segmentation to remove nonbrain tissue from the optimization routine, is presented and validated. The technique is fast, robust, and accurate, achieving the global minimum to a static field homogeneity function of the in vivo brain. Both global and specified local regions of the brain can be selected on which to optimize the shims without requiring skilled intervention. The effectiveness of the automated local shim is demonstrated in an olfactory fMRI study where significant activations in the orbitofrontal cortex were very clear when the above method was employed.