Attention-deficit/hyperactivity disorder is a highly heritable and prevalent neuropsychiatric disorder estimated to affect 6% of school-age children. Its clinical hallmarks are inattention, hyperactivity and impulsivity, which often respond substantially to treatment with methylphenidate or dextroamphetamine. Etiological theories suggest a deficit in corticostriatal circuits, particularly those components modulated by dopamine. We developed a new functional magnetic resonance imaging procedure (T2 relaxometry) to indirectly assess blood volume in the striatum (caudate and putamen) of boys 6-12 years of age in steady-state conditions. Boys with attention-deficit/hyperactivity disorder had higher T2 relaxation time measures in the putamen bilaterally than healthy control subjects. Relaxation times strongly correlated with the child's capacity to sit still and his accuracy in accomplishing a computerized attention task. Daily treatment with methylphenidate significantly changed the T2 relaxation times in the putamen of children with attention-deficit/hyperactivity disorder, although the magnitude and direction of the effect was strongly dependent on the child's unmedicated activity state. There was a similar but nonsignificant trend in the right caudate. T2 relaxation time measures in thalamus did not differ significantly between groups, and were not affected by methylphenidate. Attention-deficit/hyperactivity disorder symptoms may be closely tied to functional abnormalities in the putamen, which is mainly involved in the regulation of motor behavior.
Many functional imaging studies have demonstrated age-related alterations in cerebral blood flow during the resting state. However, few studies have addressed possible differences in functional response to cerebral activation. We assessed the response of visual cortex to photic stimulation in 9 normal elderly subjects and 17 normal younger subjects with blood oxygenation level dependent functional magnetic resonance imaging. We found that the amplitude of response in elderly subjects was significantly decreased compared to younger subjects (2.5 +/- 1.0% versus 4.0 +/- 1.6%, p = 0.01), suggesting a reduction in functional activation or an age-related alteration in the coupling of blood oxygenation to focal activation.
Although the cerebellum is increasingly being viewed as a brain area involved in cognition, it typically is excluded from circuitry considered to mediate stimulant-associated behaviors since it is low in dopamine. Yet, the primate cerebellar vermis (lobules II-III and VIII-IX) has been reported to contain axonal dopamine transporter immunoreactivity (DAT-IR). We hypothesized that DAT-IR-containing vermis areas would be activated in cocaine abusers by cocaine-related cues and, in healthy humans, would accumulate DAT-selective ligands. We used BOLD fMRI to determine whether cocaine-related cues activated DAT-IR-enriched vermis regions in cocaine abusers and positron emission tomography imaging of healthy humans to determine whether the DAT-selective ligand [ 11 C]altropane accumulated in those vermis regions. Cocaine-related cues selectively induced BOLD activation in lobules II-III and VIII-IX in cocaine users, and, at early time points after ligand administration, we found appreciable [ 11 C]altropane accumulation in lobules VIII-IX, possibly indicating DAT presence in this region. These data suggest that parts of cerebellar vermis mediate cocaine's persisting and acute effects. In light of prior findings illustrating vermis connections to midbrain dopamine cell body regions, established roles for the vermis as a locus of sensorimotor integration and motor planning, and findings of increased vermis activation in substance abusers during reward-related and other cognitive tasks, we propose that the vermis be considered one of the structures involved in cocaine-and other incentive-related behaviors.
A rapid, in-plane image registration algorithm that accurately estimates and corrects for rotational and translational motion is described. This automated, one-pass method achieves its computational efficiency by decoupling the estimation of rotation and translation, allowing the application of rapid cross-correlation and cross-spectrum techniques for the determination of displacement parameters. k-space regridding and modulation techniques are used for image correction as alternatives to linear interpolation. The performance of this method was analyzed with simulations and echo-planar image data from both phantoms and human subjects. The processing time for image registration on a Hewlett-Packard 735/125 is 7.5 s for a 128 x 128 pixel image and 1.7 s for a 64 x 64 pixel image. Imaging phantom data demonstrate the accuracy of the method (mean rotational error, -0.09 degrees; standard deviation = 0.17 degrees; range, -0.44 degrees to +0.31 degrees; mean translational error = -0.035 pixels; standard deviation = 0.054 pixels; range, -0.16 to +0.06 pixels). Registered human functional imaging data demonstrate a significant reduction in motion artifacts such as linear trends in pixel time series and activation artifacts due to stimulus-correlated motion. The advantages of this technique are its noniterative one-pass nature, the reduction in image degradation as compared to previous methods, and the speed of computation.
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