Positive correlations in metabolic rates are presumed to infer regional connectivity and/or functional correlation. Activation studies have been limited to isolated events related to very specific tasks. However, brain function presumably involves the activation of multiple interrelated systems. We have used a cortical parcellation method based on Brodmann's areas and anatomically standardized basal forebrain to investigate regional connectivity as follows: Subjects underwent structural MRI and 18-FDG-PET scanning following a verbal learning task. MRI and PET images were coregistered using a surface-matching method. Both were resliced to the AC-PC plane, and anatomical standardization carried out using a three-dimensional spline-warping transformation. Using a parcellation map based on Brodmann's areas, glucose metabolic rates for cortical sectors was calculated. Correlation coefficients between relative glucose metabolic rates in one Brodmann's area and every pixel in selected regions of interest were cal...

The main olfactory bulb (MOB) is the first olfactory center where the olfactory information is coded and processed. In addition to integrating the activity from the olfactory epithelium, the responsive behavior is regulated further by intrinsic bulbar circuits and the extrinsic pathways from other brain regions. We are using functional magnetic resonance imaging (fMRI) to visualize the integrative effects of the regulation mechanisms on bulbar responsive behavior in rats. Using iso-amyl acetate as stimulant, the effects of odorant concentration, exposure duration, and intervals between stimulations on the responsive properties of the MOB were examined at 7-Tesla with spatial resolution of 220x220x250 μm and temporal resolution of 8s to 1.5 s/image. When rat was repeatedly exposed to odors, its MOB was activated to higher degree in the first stimulation, but was suppressed in following exposures. With longer stimulation, or higher concentration, the adaptation is more prominent. Activity dropped to ∼40% of ...

Linguistic processing is a complex skill with several dissociable components, including semantic, phonological, and syntactic processing. The goal of the present study was to compare and contrast the patterns of cortical activity associated with each of these processes. Twelve healthy young adults were scanned while performing match-to-sample tasks meant to elicit three different types of language processing. The semantic task required choosing a synonym, the phonological task required choosing a rhyme from among two words ending with the same sequence of letters, and the syntactic task required choosing a verb to agree in number with a singular or plural noun. Each of these tasks was compared to a control task of choosing an identical match in an alternating block sequence. Thus the format of the stimulus and the format of the response remained constant across all conditions, and only the linguistic basis of the decision varied. Imaging was performed using a 1.5 T whole-body MRI scanner with a full head c...

Functional magnetic resonance imaging (fMRI) has been widely used for mapping blood oxygen level dependent (BOLD) signals as a marker of neuronal activity in the conscious human and nonhuman primate brain. Our group has reported mapping drug-induced changes in the basal ganglia by multiple gradient recalled echo fMRI in anesthetized as well as in alert rhesus monkeys. In addition to extensive demands placed on training and animal handling, new techniques of data analysis and statistical assessment are required to appropriately evaluate the pharmacological response as measured by MRI in alert animals. In this study we examined the use of robust multivariate statistical methods such as principal component analysis (PCA). These methods are data driven and make no a priori assumptions about timing or dynamic nature of the drug-induced temporal response. However, since they are based on variance summaries, the resulting principal components of the response are heavily influenced by the presence of aberrant or s...

Functional magnetic resonance imaging (FMRI) was used to identify candidate language processing areas in the intact human brain. Language was defined broadly to include both phonological and lexical–semantic functions and to exclude sensory, motor, and general executive functions. The language activation task required phonetic and semantic analysis of aurally presented words and was compared with a control task involving perceptual analysis of nonlinguistic sounds. Functional maps of the entire brain were obtained from 30 right-handed subjects. These maps were averaged in standard stereotaxic space to produce a robust “average activation map” that proved reliable in a split-half analysis. As predicted from classical models of language organization based on lesion data, cortical activation associated with language processing was strongly lateralized to the left cerebral hemisphere and involved a network of regions in the frontal, temporal, and parietal lobes. Less consistent with classical models were (1) t...

Associative learning is a dynamic process that allows us to incorporate new knowledge within existing semantic networks. Even after years, a seemingly stable association can be altered by a single significant experience. Here, we investigate whether the acquisition of new associations affects the neural representation of stimuli and how the brain categorizes stimuli according to preexisting and emerging associations. Functional MRI data were collected during a differential fear conditioning procedure and at test (4–5 weeks later). Two pictures of faces and two pictures of houses served as stimuli. One of each pair coterminated with a shock in half of the trials (partial reinforcement). Applying Multivoxel Pattern Analysis (MVPA) in a trial-by-trial manner, we quantified changes in the similarity of neural representations of stimuli over the course of conditioning. Our findings show an increase in similarity of neural patterns throughout the cortex on consecutive trials of the reinforced stimuli. Furthermor...

Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)—a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N = 116 healthy adults (20–79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM–age associations were identified in several ...

White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion by q -space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination,...

Sensory processing deficits in schizophrenia have been documented for several decades, but their underlying neurophysiological substrates are still poorly understood. In the visual system, the pattern of pathophysiology reported in several studies is suggestive of dysfunction within the magnocellular visual pathway beginning in early sensory cortex or even subcortically. The present study used functional magnetic resonance imaging to investigate further the neurophysiological bases of visual processing deficits in schizophrenia and in particular the potential role of magnocellular stream dysfunction. Sinusoidal gratings systematically varying in spatial frequency content were presented to subjects at low and high levels of contrast to differentially bias activity in magnocellular and parvocellular pathways based on well established differences in neuronal response profiles. Hemodynamic responses elicited by different spatial frequencies were mapped over the occipital lobe and then over the entire brain. Re...

Although Congenital Central Hypoventilation Syndrome (CCHS) patients show impaired ventilatory responses to CO2 and reduced drive to breathe during sleep, affected patients increase ventilation to passive limb motion, indicating a degree of preserved integration of cyclic locomotor systems with respiration. Functional magnetic resonance imaging (fMRI) procedures can examine the neural processes mediating limb movement integration with respiratory patterns in CCHS. We examined brain fMRI signal changes in 16 CCHS patients and 32 age- and gender-matched control subjects to passive right foot movement. Each fMRI series consisted of 175 volumes over 350 s, with an initial 70 s baseline, three 40 s challenges separated by 40 s rest periods, and ending with 80 s baseline. Images were motion corrected, spatially normalized, and smoothed. Brain regions with altered fMRI responses between groups were determined using SPM2 (boxcar model, random effects, analysis of covariance, age as covariate, threshold P < 0.01), ...