Rates of serotonin synthesis were measured in the human brain using positron emission tomography. The sensitivity of the method is indicated by the fact that measurements are possible even after a substantial lowering of synthesis induced by acute tryptophan depletion. Unlike serotonin levels in human brain, which vary greatly in different brain areas, rates of synthesis of the indolamine are rather uniform throughout the brain. The mean rate of synthesis in normal males was found to be 52% higher than in normal females; this marked difference may be a factor relevant to the lower incidence of major unipolar depression in males. Low brain serotonin (5-HT) levels or function have been implicated in various types of psychopathology, including depression, suicide, aggression, anxiety, and bulimia (for reviews see refs. 1-3). Until recently, the principal methods for studying serotonin metabolism in human brain were determination of the metabolite of serotonin 5-hydroxyindole-3-acetic acid (5-HIAA) in cerebrospinal fluid (CSF) and postmortem measurements of brain serotonin and 5-HIAA. Both methods have limitations. In particular, neither provides a direct measure of serotonin synthesis in the living brain. Recently, a method for measuring serotonin synthesis in the brain of living mammals has been developed (4-5) and tested successfully in dogs (6). The method uses positron emission tomography (PET) and ␣-[11 C]methyl-L-tryptophan as a tracer. The tracer is converted in part to ␣-[11 C]methylserotonin, which accumulates in serotonin neurons, because it is not a substrate for monoamine oxidase and does not cross the bloodbrain barrier.We report here in vivo measurements of serotonin synthesis in the brain of healthy volunteers. Both male and female subjects were studied because CSF studies suggest that the rate of brain serotonin metabolism is higher in females than in males (7-8), and because the incidence of major unipolar depression is higher in women (9). We measured rates of serotonin synthesis under two conditions: at baseline and after acute tryptophan depletion (ATD). For ATD, subjects ingest a tryptophan-free mixture of all the essential amino acids. This induces protein synthesis, which incorporates body stores of free tryptophan into protein, thus reducing the level of this amino acid in tissues, including brain (10). Because tryptophan is the precursor of serotonin, its reduction is thought to lower the rate of serotonin synthesis in brain (11-12). ATD was used in the present study for several reasons. First, low serotonin levels have been proposed to relate to various types of psychopathology (for reviews see refs. 1-3), so any useful method of in vivo measurements of the serotonin synthesis rate must have a demonstrated capability for measuring low rates of serotonin synthesis. Second, ATD induces a transient reappearance of depressive symptoms in patients under treatment with antidepressants (13). Moreover, ATD also produces a mild lowering of mood in normal subjects with a family history of de...
Brain activity associated with voluntary muscle relaxation was examined by applying event-related functional magnetic resonance imaging (fMRI) technique, which enables us to observe change of fMRI signals associated with a single motor trial. The subject voluntarily relaxed or contracted the right upper limb muscles. Each motor mode had two conditions; one required joint movement, and the other did not. Five axial images covering the primary motor area (M1) and supplementary motor area (SMA) were obtained once every second, using an echoplanar 1.5 tesla MRI scanner. One session consisted of 60 dynamic scans (i.e., 60 sec). The subject performed a single motor trial (i.e., relaxation or contraction) during one session in his own time. Ten sessions were done for each task. During fMRI scanning, electromyogram (EMG) was monitored from the right forearm muscles to identify the motor onset. We calculated the correlation between the obtained fMRI signal and the expected hemodynamic response. The muscle relaxation showed transient signal increase time-locked to the EMG offset in the M1 contralateral to the movement and bilateral SMAs, where activation was observed also in the muscle contraction. Activated volume in both the rostral and caudal parts of SMA was significantly larger for the muscle relaxation than for the muscle contraction (p < 0.05). The results suggest that voluntary muscle relaxation occurs as a consequence of excitation of corticospinal projection neurons or intracortical inhibitory interneurons, or both, in the M1 and SMA, and both pre-SMA and SMA proper play an important role in motor inhibition.
In women of reproductive age, 18F-FDG imaging should preferably be done within a week before or a few days after the menstrual flow phase to avoid any misinterpretation of pelvic 18F-FDG PET images.
With a large database, we aimed to evaluate sex-specific distinctive changes in brain glucose metabolism and morphology during normal aging using MRI and 18 F-FDG PET. Methods: A total of 963 cognitively healthy adults were included in this study. All subjects completed a medical questionnaire, took the mini-mental state examination, and underwent brain MRI and whole-body 18 F-FDG PET. The MR and PET images were statistically analyzed using 3-dimensional stereotactic surface projection. All images were corrected for whole-brain pixel value to identify the brain regions with significant changes, and regions of interest were set up with reference to Brodmann areas. We evaluated morphologic and glucose metabolic changes by cross-sectional analysis. The baseline database consisted of subjects from 30 to 40 y old, and the age-step for comparison was 5-y ranges. We also compared sex-specific differences in MR and PET images in each age group. Results: Regarding age-related changes, in both sexes brain atrophy was observed in the lateral frontal and parietal regions and glucose hypometabolism in the medial frontal regions. There were significant differences in these parameters between the sexes; parallel changes in volume and metabolism were manifested in the medial frontal cortex in men and in the lateral and medial temporal cortex in women. By contrast, metabolism-dominant reductions were manifested in the lateral and medial parietal cortex in men and in the ventrolateral prefrontal cortex, including the Broca area, in women. These differences became insignificant in individuals 66 y or older. Conclusion: Our brain mapping study with a large number of reference human brain data demonstrated age-related parallel changes between morphology and metabolism in the medial frontal regions and sex-specific hypometabolism in the parietal (male) and ventrolateral prefrontal (female) cortices. These findings may suggest an aging vulnerability in sex-specific brain regions: the parietal cortex for visuospatial ability in men and the Broca area for speech processing in women. The current trend of an increase in the number of dementia patients, including those with Alzheimer disease (AD) (1), as well as the revised criteria for the diagnosis of dementia by the National Institute on Aging and the Alzheimer's Association (2-5), has brought researchers to place greater attention on early, preclinical, detection of changes in brain physiology. Indeed, in familial AD, pathologic changes in the brain seem to develop 25 y before the onset of clinical symptoms (6).To detect the preclinical stage of AD, it is necessary to catch subtle deviations from the healthy brain and, thus, to know the morphology and activity of a healthy brain for comparison. Several studies have used MRI or PET on cognitively normal people to evaluate age-related changes and sex-specific differences in the brain. To the best of our knowledge, however, the sexspecific differences in brain morphology and metabolism found by previous brain imaging studies were only in ...
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