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Udgivelsesdato: 2010-Feb-15 PET studies with the DOPA decarboxylase substrate 6-[(18)F]fluoro-l-DOPA (FDOPA) reveal the storage of [(18)F]-fluorodopamine within synaptic vesicles, mainly of dopamine fibres. As such, FDOPA PET is a sensitive indicator of the integrity of the nigrostriatal dopamine innervation. Nonetheless, there have been several reports of focal elevations of FDOPA utilization in brain of patients with Parkinson's disease (PD), all based on reference tissue methods. To investigate this phenomenon further, we used voxel-wise steady-state kinetic analysis to search for regions of elevated FDOPA utilization (K; ml g(-1) min(-1)) and steady-state trapping (V(d); ml g(-1)) in a group of well-characterized patients with early, asymmetric PD, who were contrasted with an age-matched control group. Subtraction of the population mean parametric maps revealed foci of increased FDOPA utilization K (+25%) in the bilateral medial nucleus accumbens, whereas the expected declines in the trapping of FDOPA were seen in the caudate and putamen. This observation suggests hyperfunction of catecholamine fibres innervating specifically the limbic striatum, which could guide the design of future prospective FDOPA-PET studies of the impulse control disorders occurring in some PD patients under treatment with dopamine agonists. A focus of increased FDOPA influx and also V(d) was detected in the periaqueductal grey, consistent with some earlier reports based on reference tissue analysis. Increased FDOPA trapping in the periaqueductal grey of PD patients seems consistent with recent reports of increased activity of serotonin neurons in a rat model of parkinsonism.

Udgivelsesdato: 2008-Apr-1 INTRODUCTION: In positron emission tomography (PET) studies of cerebral blood flow (CBF) and metabolism, the large interindividual variation commonly is minimized by normalization to the global mean prior to statistical analysis. This approach requires that no between-group or between-state differences exist in the normalization region. Given the variability typical of global CBF and the practical limit on sample size, small group differences in global mean easily elude detection, but still bias the comparison, with profound consequences for the physiological interpretation of the results. MATERIALS AND METHODS: Quantitative [15O]H2O PET recordings of CBF were obtained in 45 healthy subjects (21-81 years) and 14 patients with hepatic encephalopathy (HE). With volume-of-interest (VOI) and voxel-based statistics, we conducted regression analyses of CBF as function of age in the healthy group, and compared the HE group to a subset of the controls. We compared absolute CBF values, and CBF normalized to the gray matter (GM) and white matter (WM) means. In additional simulation experiments, we manipulated the cortical values of 12 healthy subjects and compared these to unaltered control data. RESULTS: In healthy aging, CBF was shown to be unchanged in WM and central regions. In contrast, with normalization to the GM mean, CBF displayed positive correlation with age in the central regions. Very similar artifactual increases were seen in the HE comparison and also in the simulation experiment. CONCLUSION: Ratio normalization to the global mean readily elevates CBF in unchanged regions when a systematic between-group difference exists in gCBF, also when this difference is below the detection threshold. We suggest that the routine normalization to the global mean in earlier studies resulted in spurious interpretations of perturbed CBF. Normalization to central WM yields less biased results in aging and HE and could potentially serve as a normalization reference region in other disorders as well.

Udgivelsesdato: 2006-Jun The left inferior prefrontal cortex (LIPC) is involved in speech comprehension by people who hear normally. In contrast, functional brain mapping has not revealed incremental activity in this region when users of cochlear implants comprehend speech without silent repetition. Functional brain maps identify significant changes of activity by comparing an active brain state with a presumed baseline condition. It is possible that cochlear implant users recruited alternative neuronal resources to the task in previous studies, but, in principle, it is also possible that an aberrant baseline condition masked the functional increase. To distinguish between the two possibilities, we tested the hypothesis that activity in the LIPC characterizes high speech comprehension in postlingually deaf CI users. We measured cerebral blood flow changes with positron emission tomography (PET) in CI users who listened passively to a range of speech and non-speech stimuli. The pattern of activation varied with the stimulus in users with high speech comprehension, unlike users with low speech comprehension. The high-comprehension group increased the activity in prefrontal and temporal regions of the cerebral cortex and in the right cerebellum. In these subjects, single words and speech raised activity in the LIPC, as well as in left and right temporal regions, both anterior and posterior, known to be activated in speech recognition and complex phoneme analysis in normal hearing. In subjects with low speech comprehension, sites of increased activity were observed only in the temporal lobes. We conclude that increased activity in areas of the LIPC and right temporal lobe is involved in speech comprehension after cochlear implantation.

Udgivelsesdato: 2005-Apr-15 Abnormal central dopamine (DA) neurotransmission has been implicated in the impulsivity, inattention, and hyperactivity of attention deficit hyperactivity disorder (ADHD). We hypothesized that a pharmacological challenge with methylphenidate (MP) at a therapeutic dose increases extracellular DA concentrations in proportion to the severity of these specific ADHD symptoms. To test this hypothesis, we measured by PET the effect of acute challenge with MP on the availability of striatal binding sites for [11C]raclopride (pB), an index of altered interstitial DA concentration, in nine unmedicated adolescents (1 female, 8 males; age 13.7 +/- 1.8 years) with a current diagnosis of ADHD. We estimated the pB of [11C]raclopride for brain dopamine D2/3 receptors first in a baseline resting condition, and again after an acute challenge with MP (0.3 mg/kg, p.o.), and calculated the percentage change in (%DeltapB) in left and right striatum. On another day, measurements of impulsivity and inattention were performed using a computerized continuous performance test. There was a significant correlation between the magnitude of %DeltapB in the right striatum and the severity of inattention and impulsivity. MP-evoked %DeltapB correlated with standard scores for impulse control (r = 0.68; P = 0.02), attention (r = 0.81; P = 0.005), information processing (r = 0.66; P = 0.02), and consistency of attention, or variability (r = 0.60; P = 0.04). In conclusion, the results link inattention and impulsivity with sensitivity of brain DA receptor availability to an MP challenge, corroborating the hypothesis that MP serves to potentiate decreased DA neurotransmission in ADHD.

Musicians exchange non-verbal cues as messages when they play together. This is particularly true in music with a sketchy outline. Jazz musicians receive and interpret the cues when performance parts from a regular pattern of rhythm, suggesting that they enjoy a highly developed sensitivity to subtle deviations of rhythm. We demonstrate that pre-attentive brain responses recorded with magnetoencephalography to rhythmic incongruence are left-lateralized in expert jazz musicians and right-lateralized in musically inept non-musicians. The left-lateralization of the pre-attentive responses suggests functional adaptation of the brain to a task of communication, which is much like that of language.

Udgivelsesdato: 2004-Feb The relationships among cerebral blood flow (CBF), oxygen consumption (CMRO(2)) and glucose use (CMR(glc)) constitute the basis of functional brain-imaging. Here we report spatially dissociated changes of CMRO(2) and CBF during motor activity that lead us to propose a revision of conventional CBF-CMRO(2) coupling models. In the left primary and supplementary motor cortices, CBF and CMRO(2) rose significantly during finger-thumb tapping. However, in the right putamen CBF did not rise, despite a significant increase in CMRO(2). We explain these observations by invoking a central command mechanism that regulates CBF in the putamen in anticipation of movement. By this mechanism, CBF rose in the putamen before the measurements of CBF and CMRO(2) while CMRO(2) rose when actual motion commenced.

We tested the prediction that single photon emission computed tomography (SPECT) of the blood flow distribution in speech-activated brain identifies the language-dominant hemisphere. We based the prediction on the hypothesis that language activation leads to focally increased regional cerebral blood flow (rCBF), which is reflected in the uptake of a flow tracer recorded by SPECT. We compared the results of speech activation to the results of functional transcranial Doppler (fTCD) monitoring in the same subjects. Preoperatively, 17 patients (10 women and 7 men with a mean age of 36 +/- 15 years) with diagnoses of epilepsy (n = 14) or arteriovenous malformation (AVM) (n = 3) had two SPECT and two stereo-TCD monitoring studies in each case, one at rest, and one during 3 min of speech activation. Except for two left-handed patients with right-hemisphere dominance, the subjects had the highest changes of rCBF from baseline to activation in the left posterior inferior frontal cortex and in contralateral cerebellum. The results show that changes of the level of neuronal activity reflected by the measurement of rCBF variations might be detected by SPECT. Additionally, the evaluation of hemispheric language dominance based on SPECT showed a complete agreement with the evaluation based on fTCD results (yielding a kappa coefficient equal to 1), and therefore, speech-activation SPECT mapping might be helpful in the evaluation of hemispheric language dominance, especially when fMRI and PET are not available or they are contraindicated for some reason.

Udgivelsesdato: 2001-Dec We have used positron emission tomography to investigate the cortical areas of the normal human brain involved in processing inward (Expansion) and outward (Contraction) radial motion simulated with an optic flow stimulus. The optical flow display was made out of dots moving radially away from or toward the center of the display monitor. In the Control condition, the dots' motion was randomized in order to remove any sensation of radial motion. In the Expansion condition, several loci of activation were observed: visual areas V2-V3 and the superior parietal lobule (BA 7), predominantly in the right hemisphere. In the Contraction condition activation sites were found in the same visual areas (V2 and V3) in the right hemisphere but the increase in rCBF in these regions was much lower than in the Expansion condition. BA 7 was activated in both hemispheres. When the motion component of the stimulus was isolated by subtracting the static condition from the incoherent motion condition, we obtained activations of areas V2, V3, and MT (putative V5). These results indicate that the detection of radial motion derived from an optic flow stimulus is mediated by structures forming the dorsal part of the visual cortical system and confirm that area MT is not specifically involved in flow analysis.

Udgivelsesdato: 1999-Sep Neuropsychological data suggests that divided attention is more impaired than sustained attention during the early phases of Alzheimer's disease. The purpose of the present study was to compare cerebral activation patterns during sustained and divided attention between Alzheimer patients and healthy elderly. The O-15-water PET activation method was used to map sustained and divided attention in 16 patients with Alzheimer's disease (mean age +/- SD: 68 +/- 5 years; MMSE: 11-25, mean +/- SD = 19.5 +/- 4.9) and in 16 healthy age-matched control subjects. After stereotactical normalization, voxel-by-voxel t statistics was used to assess the significance of activated brain areas and to compare activations between patients and control subjects. In the healthy elderly, sustained and divided attention both elicited activation of the right inferior parietal lobule, and the right middle frontal gyrus, whereas the anterior cingulate gyrus was activated during sustained attention only. Only medial frontal structures (Brodmann Area (BA) 32/34) were activated in Alzheimer patients, and both frontal (BA-10), posterior cingulate (BA-23/31), and subcortical sites were deactivated. Compared to the healthy elderly, the activations in the patients of the right medial (BA-11) superior (BA-10) and inferior (BA-47) frontal gyri, the right middle temporal (BA-20), and the left lingual (BA-17) gyri were significantly reduced. More cortical sites differed statistically between Alzheimer patients and control subjects during divided than during sustained attention. The activation pattern elicited by attention supports the neuropsychological data that divided attention is more impaired than sustained attention in early Alzheimer's disease.

Musicians exchange non-verbal cues as messages when they play together. This is particularly true in music with a sketchy outline. Jazz musicians receive and interpret the cues when performance parts from a regular pattern of rhythm, suggesting that they enjoy a highly developed sensitivity to subtle deviations of rhythm. We demonstrate that pre-attentive brain responses recorded with magnetoencephalography to rhythmic incongruence are left-lateralized in expert jazz musicians and right-lateralized in musically inept non-musicians. The left-lateralization of the pre-attentive responses suggests functional adaptation of the brain to a task of communication, which is much like that of language.

We tested the prediction that single photon emission computed tomography (SPECT) of the blood flow distribution in speech-activated brain identifies the language-dominant hemisphere. We based the prediction on the hypothesis that language activation leads to focally increased regional cerebral blood flow (rCBF), which is reflected in the uptake of a flow tracer recorded by SPECT. We compared the results of speech activation to the results of functional transcranial Doppler (fTCD) monitoring in the same subjects. Preoperatively, 17 patients (10 women and 7 men with a mean age of 36 +/- 15 years) with diagnoses of epilepsy (n = 14) or arteriovenous malformation (AVM) (n = 3) had two SPECT and two stereo-TCD monitoring studies in each case, one at rest, and one during 3 min of speech activation. Except for two left-handed patients with right-hemisphere dominance, the subjects had the highest changes of rCBF from baseline to activation in the left posterior inferior frontal cortex and in contralateral cerebellum. The results show that changes of the level of neuronal activity reflected by the measurement of rCBF variations might be detected by SPECT. Additionally, the evaluation of hemispheric language dominance based on SPECT showed a complete agreement with the evaluation based on fTCD results (yielding a kappa coefficient equal to 1), and therefore, speech-activation SPECT mapping might be helpful in the evaluation of hemispheric language dominance, especially when fMRI and PET are not available or they are contraindicated for some reason.

Udgivelsesdato: 1997-Oct Human brain mechanisms subserving attention have been assigned to prefrontal, midfrontal, and posterior parietal cortices, as well as to the anterior cingulate and the thalamus. To map these mechanisms in the brain, most studies have used selective attention tasks; few studies have mapped the brain under sustained or divided attention. The present study was designed to create maps of regional activity associated with sustained and divided attention using two different sensory modalities: visual checkerboard stimulation and vibrotactile stimulation of the right hand. Five cerebral PE-tomograms of 15O-labeled water uptake were acquired from 16 elderly healthy subjects during sustained or divided attention to the frequency of stimulation. To locate active brain regions, the t-statistic map of relative changes in cerebral blood flow was coregistered to the subjects' averaged brain MR images and to the standard Talairach brain coordinate system. Attention was associated with activity in two sites, the right middle frontal gyrus (Brodmann area 46) and the right inferior parietal lobule (Brodmann area 40). The frontal site was more active when the subjects attended to the visual stimulus and when the attention was divided, while the parietal site was more active during attention to the vibrotactile stimulus and during simple sustained attention. Our observations are consistent with the hypotheses (1) that the right posterior parietal attention center subserves attention to several sensory modalities and (2) that a cortical network of specific neuronal sites subserves both sustained and divided attention. These hypotheses must be tested in further studies.