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This study evaluates the intra- and inter-subject variability of digit maps in area 3b of anesthetized squirrel monkeys. Maps were collected using high field blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). BOLD responses to individual digit stimulations were mapped and their response properties (location, area of activation, % signal change, time to peak response) were compared within and across imaging sessions separated by up to 20 months. During single digit stimulation using a block design, the spatiotemporal response of the BOLD signal for individual runs within and across sessions and animals was well conserved, with a time to peak BOLD response of 20+/-4 s. The variability in the center of BOLD activation in area 3b was 0.41+/-0.24 mm (mean+/-SD) across individual 5-7 min runs within a scanning session and 0.55+/-0.15 mm across sessions. The average signal change across all animals, runs and sessions was 0.62+/-0.38%, and varied 32% within and 40% across sessions. In a comparison of the stability and reproducibility of the area of single digit activation obtained using three approaches, use of a fixed statistical threshold (P<10(-5)) yielded an average area of 4.8+/-3.5 mm(2) (mean+/-SD), adaptive statistical thresholding 1.32+/-1.259 mm(2) (mean+/-SD), and combined fixed statistical and adaptive BOLD signal amplitude 4.4+/-2.5 mm(2) (mean+/-SD) across image runs and sessions. The somatotopic organization was stable within animals across sessions, while across animals, there was some variation in overall activation pattern and inter-digit distances. These results confirm that BOLD activation maps of single digits in area 3b as characterized by activation center, signal amplitudes, and temporal profile are very stable. The activation sizes determined by various criteria are the most variable measure in this preparation, but adaptive statistical thresholding appears to yield the most stable and reproducible maps. This study serves as a baseline assessment of the limits imposed on the detection of plastic changes by experimental variations of the digit BOLD fMRI activation maps in normal animals, and as an indicator of the likely performance limits in human studies.

We identified human brain regions involved in the perception of sad, frightened, happy, angry, and neutral facial expressions using functional magnetic resonance imaging (fMRI). Twenty-one healthy right-handed adult volunteers (11 men, 10 women; aged 18-45; mean age 21.6 years) participated in four separate runs, one for each of the four emotions. Participants viewed blocks of emotionally expressive faces alternating with blocks of neutral faces and scrambled images. In comparison with scrambled images, neutral faces activated the fusiform gyri, the right lateral occipital gyrus, the right superior temporal sulcus, the inferior frontal gyri, and the amygdala/entorhinal cortex. In comparisons of emotional and neutral faces, we found that (1) emotional faces elicit increased activation in a subset of cortical regions involved in neutral face processing and in areas not activated by neutral faces; (2) differences in activation as a function of emotion category were most evident in the frontal lobes; (3) men showed a differential neural response depending upon the emotion expressed but women did not.

We report a patient with rapidly accelerating HIV dementia accompanied by seizures and an unusual movement disorder despite highly potent antiretroviral therapy. This clinical constellation was associated with the non-parenteral use of methamphetamine and cocaine. Fractional enhancement time on post contrast magnetic resonance imaging studies revealed a progressive breakdown of the blood brain barrier particularly in the basal ganglia. The movement disorder but not the dementia responded to a combination of dopamine replacement and anticholinergic therapy. While the movement disorder may have been unmasked by concomitant anticonvulsant therapy, we suggest in this instance, that prior drug abuse synergized with HIV to cause a domino effect on cerebral function. Careful attention and analysis to histories of remote non-injecting drug abuse may help substantiate our hypothesis.

Functional magnetic resonance imaging (fMRI) was used to analyze blood oxygen level-dependent (BOLD) responses in the nigrostriatal system (caudate nucleus, putamen and substantia nigra) of awake rhesus monkeys to systemic apomorphine administration. The study (1) measured BOLD responses as an index of neuronal activity in the three structures following injections of the mixed D1/D2 agonist, and (2) assessed the effects of isoflurane anesthesia on the fMRI responses. Compared to control saline injections, 0.1 mg/kg apomorphine significantly activated the caudate nucleus (P < or = 0.005), putamen (P < or = 0.001) and substantia nigra (P < or = 0.005). The responses were consistent with activation of GABAergic neurons in these three structures seen in other animal models. Isoflurane gas measurably blunted the response to apomorphine, so that a significant apomorphine activation was only seen in the substantia nigra of anesthetized animals. Even there, the mean MR signal change was reduced from 9.8% in awake monkeys to 2.3% in anesthetized animals. The data support the hypothesis that fMRI can be used to study the effects of drugs that alter basal ganglia activity in awake rhesus monkeys.

Functional MRI (fMRI) was used to study striatal sensitivity to levodopa in hemiparkinsonian rhesus monkeys. Responses consistent with increased neuronal activity were seen in areas whose normal dopaminergic input from the substantia nigra pars compacta had been ablated by MPTP. Sites of increased activity following levodopa included the lateral putamen, the ventral region of the caudate head, septal areas, and midlateral amygdala in the MPTP-lesioned hemisphere. Increased activity was also observed in the same areas in the nonlesioned hemisphere, but was less pronounced in spatial extent and magnitude, suggesting either subclinical contralateral damage and/or functional adaptations in the contralateral dopamine systems. The increases in neuronal activity following levodopa treatment were temporally correlated with increases in striatal dopamine levels. Chronic levodopa treatment reduced behavioral responsiveness to levodopa and abolished the fMRI response. These results suggest that fMRI can detect changes in dopamine receptor-mediated neuronal sensitivity to dopaminergic agents.

Principal component analysis (PCA) is one of several structure-seeking multivariate statistical techniques, exploratory as well as inferential, that have been proposed recently for the characterization and detection of activation in both PET and fMRI time series data. In particular, PCA is data driven and does not assume that the neural or hemodynamic response reaches some steady state, nor does it involve correlation with any pre-defined or exogenous experimental design template. In this paper, we present a generalized linear systems framework for PCA based on the singular value decomposition (SVD) model for representation of spatio-temporal fMRI data sets. Statistical inference procedures for PCA, including point and interval estimation will be introduced without the constraint of explicit hypotheses about specific task-dependent effects. The principal eigenvectors capture both the spatial and temporal aspects of fMRI data in a progressive fashion; they are inherently matched to unique and uncorrelated features and are ranked in order of the amount of variance explained. PCA also acts as a variation reduction technique, relegating most of the random noise to the trailing components while collecting systematic structure into the leading ones. Features summarizing variability may not directly be those that are the most useful. Further analysis is facilitated through linear subspace methods involving PC rotation and strategies of projection pursuit utilizing a reduced, lower-dimensional natural basis representation that retains most of the information. These properties will be illustrated in the setting of dynamic time-series response data from fMRI experiments involving pharmacological stimulation of the dopaminergic nigro-striatal system in primates.

Multispectral automated segmentation of MR images of the brains of 10 young (5-8 years), 10 middle-aged (12-17 years), and 11 old (21-27 years) female rhesus monkeys revealed age-associated changes in brain volume and composition. Total brain parenchymal volume (expressed as fraction of intracranial volume-%ICV) decreased at a linear rate of 0.3+/-0.04% ICV/year. Up to age approximately 15 years, this loss was almost entirely due to gray matter loss, with a compensatory increase in cerebrospinal fluid (CSF), and possibly some white matter. Brain tissue composition, expressed as the gray matter/white matter volume ratio confirmed that gray matter loss exceeded white matter loss, but the rate of decline in the gray/white ratio began to slow after approximately 15 years. Comparison of these age-associated changes in rhesus brain with those in humans suggest that the brain aging in rhesus is a good model of human brain aging, but occurs approximately 3-fold faster., (Copyright 1999 Elsevier Science B.V.)

Functional magnetic resonance imaging was used to detect cortical activation in the right and left perisylvian cortex of seven young adult right-handed volunteers in response to a letter fluency task and to a visual naming task using standardized line drawings. Both letter fluency and visual naming activated left dorsolateral prefrontal cortex (Brodmann's areas 6, 9, 44 and 45). Only visual naming activated area 37 (a cortical region with strong connections to visual association areas), visual association area 19, and areas 39 and 21 previously shown to activate with auditory semantic tasks. This study supports a role for area 37 as participant in a visual lexicosemantic processing network which may otherwise overlap the auditorysemantic network.

31P Magnetic resonance spectroscopy of the frontal lobe was performed in 17 patients with Alzheimer's disease (AD), 8 elderly controls (EC), and 17 young controls (YC). The phosphocreatine/inorganic phosphate (PCr/Pi) ratio in AD (2.32 +/- 0.26 SD) was significantly lower than in EC (2.65 +/- 0.41). In AD patients, a correlation was observed between the PCr/Pi ratio and the dementia rating scale (r = -0.50, p = 0.04). A significant positive correlation between PCr/Pi ratio and age was observed in both AD (r = 0.67, p = 0.003) and YC (r = 0.63, p = 0.006) groups, however, suggesting caution in interpretation of this ratio in AD. We did not find differences between AD, EC, or YC in any other spectroscopic measure. A significant sex difference in the phosphomonoester/phosphodiester ratio (PME/PDE) ratio was observed in AD brain. Females had a lower PME/PDE ratio than males.

Disorders of the CNS are the major causes of morbidity and mortality observed in untreated subjects with phenylketonuria (PKU). A method to measure cerebral concentrations of phenylalanine (Phe) in vivo would greatly enhance the ability to investigate both the pathophysiology and the efficacy of therapy of this aminoacidopathy. Twelve image-guided localized proton nuclear magnetic resonance spectroscopic studies were performed in seven subjects with PKU using pulse sequences optimized to detect the aromatic protons of Phe. Ten control studies were also performed using a 2.1-Tesla Bruker Biospec spectrometer. Plasma Phe was measured at the time of the spectroscopic examination in the PKU patients. A Phe signal was observed in all 12 studies performed on the group with PKU, and in five studies cerebral Phe concentrations were measured to be 480 to 780 mumol/g. Plasma Phe concentrations were 0.7 to 3.3 mM (10.8 to 54.8 mg/dL) in the subjects with PKU. Human cerebral Phe concentrations can be measured noninvasively using proton nuclear magnetic resonance spectroscopy. A simultaneous measure of Phe and several other cerebral metabolites is obtained with this innovative technology. Adaptations of this technique can be used to investigate PKU and other neurometabolic disorders with modifications of current clinical magnetic resonance imaging systems.

The natural abundance 13C NMR intensity of the glycogen C1 resonance was measured in the surgically exposed liver of rabbits in vivo (n = 17) by integration from 98 to 104 ppm and compared double blindedly to the subsequent biochemical measurement. Coil loading was measured each time from a reference sphere at the coil center and the NMR intensity was normalized accordingly. For quantification, the normalized NMR intensity was calibrated using aqueous glycogen solutions ranging from 110 to 1100 mumol glucosyl units/g (n = 14). An in vivo range from 110 to 800 mumol glucosyl units/g wet weight was measured with a highly linear correlation with concentration (r = 0.85, P < 0.001). The in vivo NMR concentration was 0.95 +/- 0.05 (mean +/- standard error, n = 17) of the concomitant enzymatic measurement of glycogen content. We conclude that the 13C NMR signal of liver glycogen C1 is essentially 100% visible in vivo and that natural abundance 13C NMR spectroscopy can provide reliable noninvasive estimates of in vivo glycogen content over the physiological range of liver glycogen concentrations when using adequate localization and integration procedures.