PubMed Health⌕ Search

Biomedical subjects

Albert Gjedde

Publications and source records attributed to Albert Gjedde.

At least 37 records · Page 2Linked to original sources
PubMed2005

PET studies of net blood-brain clearance of FDOPA to human brain: age-dependent decline of [18F]fluorodopamine storage capacity.

Conventional methods for the graphical analysis of 6-[(18)F]fluorodopa (FDOPA)/positron emission tomography (PET) recordings (K(in)(app)) may be prone to negative bias because of oversubtraction of the precursor pool in the region of interest, and because of diffusion of decarboxylated FDOPA metabolites from the brain. These effects may reduce the sensitivity of FDOPA/PET for the detection of age-related changes in dopamine innervations. To test for these biasing effects, we have used a constrained compartmental analysis to calculate the brain concentrations of the plasma metabolite 3-O-methyl-FDOPA (OMFD) during 120 mins of FDOPA circulation in healthy young, healthy elderly, and Parkinson's disease subjects. Calculated brain OMFD concentrations were subtracted frame-by-frame from the dynamic PET recordings, and maps of the FDOPA net influx to brain were calculated assuming irreversible trapping (K(app)). Comparison of K(in)(app) and K(app) maps revealed a global negative bias in the conventional estimates of FDOPA clearance. The present OMFD subtraction method revealed curvature in plots of K(app) at early times, making possible the calculation of the corrected net influx (K) and also the rate constant for diffusion of decarboxylated metabolites from the brain (k(loss)). The effective distribution volume (EDV(2); K/k(loss)) for FDOPA, an index of dopamine storage capacity in brain, was reduced by 85% in putamen of patients with Parkinson's disease, and by 58% in the healthy elderly relative to the healthy young control subjects. Results of the present study support claims that storage capacity for dopamine in both caudate and putamen is more profoundly impaired in patients with Parkinson's disease than is the capacity for DOPA utilization, calculated by conventional FDOPA net influx plots. The present results furthermore constitute the first demonstration of an abnormality in the cerebral utilization of FDOPA in caudate and putamen as a function of normal aging, which we attribute to loss of vesicular storage capacity.

Adult↗
PubMed2005

Cerebral metabolic response to low blood flow: possible role of cytochrome oxidase inhibition.

The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMR(O(2))) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim fails to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMR(O(2)) in five, young healthy volunteers before and during COX inhibition with indomethacin. The average CBF declined 35%, while neither regional nor average CMR(O(2)) changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.

Adult↗
PubMed2005

Emotion processing of major, minor, and dissonant chords: a functional magnetic resonance imaging study.

Musicians and nonmusicians listened to major, minor, and dissonant musical chords while their BOLD brain responses were registered with functional magnetic resonance imaging. In both groups of listeners, minor and dissonant chords, compared with major chords, elicited enhanced responses in several brain areas, including the amygdala, retrosplenial cortex, brain stem, and cerebellum, during passive listening but not during memorization of the chords. The results indicate that (1) neural processing in emotion-related brain areas is activated even by single chords, (2) emotion processing is enhanced in the absence of cognitive requirements, and (3) musicians and nonmusicians do not differ in their neural responses to single musical chords during passive listening.

Acoustic Stimulation↗
PubMed2004

MDMA-evoked changes in cerebral blood flow in living porcine brain: correlation with hyperthermia.

3,4-Methylenedioxymethamphetamine (MDMA) acutely releases intraneuronal dopamine and serotonin and evokes hyperthermia which is linked to toxicity for serotonin fibers. The acute effects of MDMA on cerebral blood flow (CBF) in living brain have not been described in an animal model of MDMA intoxication. We predicted that MDMA-induced hyperthermia should correlate with increased CBF in the hypothalamus, a serotonin-rich brain region subserving thermoregulation. To test this prediction, we used positron emission tomography with statistical parametric mapping for exploratory analysis of the focal changes in the magnitude of CBF in the anesthetized female Landrace pig (n = 9) at 30 and 150 min after acute challenge with MDMA-HCl (1 mg/kg, i.v.). The MDMA treatment was followed by increased CBF in the occipital cortex and in the medial mesencephalon overlapping the dorsal raphé nucleus, and reduced CBF in the cerebellar vermis and in a cluster in the medulla encompassing the left locus coeruleus. The individual increase of body temperature correlated positively with increased CBF in the vicinity of the raphé nucleus, in the hypothalamus (regions linked to thermoregulation), and also in the medial frontal cortex, which together comprise the regions receiving the most dense serotonin innervations in pig brain. Thus, individual differences in the susceptibility to MDMA-induced hyperthermia in this population correlated with the magnitude of focal increases in CBF within specific brain regions endowed with a dense serotonin innervation, including regions linked to thermoregulation.

Animals↗
PubMed2004

MDMA-evoked changes in [11C]raclopride and [11C]NMSP binding in living pig brain.

Positron emission tomography (PET) studies with radiolabeled dopamine D2-like receptor ligands reveal d-amphetamine-evoked increases in the competition from endogenous dopamine. However, the corresponding effects of methylenedioxymethamphetamine (MDMA, "Ecstasy"), which releases catecholamines and also serotonin, are unknown. Using PET, we measured the binding potentials (pBs) of the benzamide [11C]raclopride and the butyrophenone N-[11C]methylspiperone ([11C]NMSP) in brain of living pigs first in a baseline condition and at 45 and 165 min after infusion of (+/-)-MDMA-HCl (1 mg/kg, i.v.). Concomitant studies of cerebral blood flow did not reveal significant perfusion changes in the cerebellum reference region or in striatum, supporting the present use of reference tissue methods for the mapping of MDMA-evoked pB changes. Relative to the baseline pB of [11C]raclopride for dopamine D(2/3) receptors in striatum (pB = 1.5-2.2), MDMA-treatment reduced pB by 35% in the first posttreatment scan and by 22% in the second posttreatment scan, comparable to changes typically evoked by d-amphetamine at a similar dose. In most previous studies, the in vivo binding of butyrophenones has been nearly insensitive to d-amphetamine-evoked dopamine release. However, we found the baseline pB of [11C]NMSP for dopamine D2-like receptors in striatum (pB = 4-5) was decreased by 30% in the first post-MDMA scan and by 50% in the second post-MDMA scan, irrespective of assumptions about the extent of equilibrium binding attained during the 90-min-long PET recordings. Distinct properties of MDMA such as simultaneous release of dopamine and serotonin in brain may account for the present finding of progressive decline in the availability of [11C]NMSP binding sites in striatum.

Animals↗
PubMed2004

The Danish PET/depression project: performance on Stroop's test linked to white matter lesions in the brain.

The Stroop test (ST) assesses the integrity of prefrontal and cingulate functioning. Patients with major depression perform poorly on the ST, pointing to disturbed function in these areas. We therefore used positron emission tomography to study 41 in-patients with major depression and 46 age- and gender-matched controls during neuropsychological activation with the ST. Magnetic resonance imaging was used for coregistration and for description of the localization of white matter lesions (WML). The cerebral blood flow (CBF) changes during ST were mapped for each of the two study groups, and inter-group differences were calculated on a voxel-by-voxel basis. The patients were followed for 3 to 5 years to ensure diagnostic stability. The control group activated anterior cingulate regions, prefrontal cortices, insula, thalamus and cerebellum. Despite the patients' slower performance with more errors, no significant differences were found comparing the activations in the two groups. The performance was, however, correlated to the number of WML in frontal lobes, insula and adjacent to the basal ganglia, whereas WML in other locations was not related to performance. We thus partly explain the poorer performance by increased frequency of WML in frontostriatal pathways in the depressed patients, impairing neurotransmission.

Adult↗
PubMed2004

Recovery of anterograde amnesia in a case of craniopharyngioma.

BACKGROUND: Studies of the amnesic syndrome have indicated that telencephalic and diencephalic structures are critical components of the memory system. The exact role of the mammillary bodies (MBs) in human memory remains elusive, since few cases of selective MB damage have been reported. OBJECTIVE: To study a case of severe anterograde amnesia due to a third-ventricle craniopharyngioma with severe MB compression. DESIGN: Case report. SETTING: Neurosurgery clinic of an academic hospital. PATIENT: A 53-year old woman who developed severe anterograde amnesia due to a third-ventricle craniopharyngioma strongly compressing the MBs and, to a lesser extent, the right hippocampus. INTERVENTIONS: Surgical excision of the tumor and neuropsychological testing and positron emission tomography during an associative memory test before and 2 months after tumor removal. A postsurgical magnetic resonance image did not show evidence of damage to the hypothalamus, thalamus, hippocampus, or MBs. MAIN OUTCOME MEASURES: Changes in brain imaging data and results of neuropsychological testing. RESULTS: After tumor removal, the patient showed a complete recovery of memory functions. Performance on the associative memory test was at chance level before surgery and dramatically improved postoperatively. Results of the preoperative positron emission tomographic study showed no activity in memory-related structures. In contrast, a significant blood flow increase occurred in the anterior thalamic nuclei postoperatively. CONCLUSIONS: These behavioral and brain imaging data stress the importance of the MBs in this patient's amnesia. Our data further suggest that the clinical prognosis of decompressing the mammillothalamic tract is excellent, even in cases of massive compression.

Amnesia, Anterograde↗
PubMed2004

Spatially dissociated flow-metabolism coupling in brain activation.

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.

Adult↗
PubMed2004

ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow.

Attention-deficit-hyperactivity disorder (ADHD), while largely thought to be a genetic disorder, has environmental factors that appear to contribute significantly to the aetiopathogenesis of the disorder. One such factor is pretern birth with vulnerable cerebrovascular homeostasis. We hypothesised that cerebral ischaemia at birth could contribute to persistent deficient dopaminergic neurotransmission, which is thought to be the pathophysiological basis of the disorder. We examined dopamine D(2/3) receptor binding with positron emission tomography (PET) using [11C] raclopride as a tracer, and continuous reaction times (RT) with a computerized test of variables (TOVA) in six adolescents (12-14 years of age, one female) who had been examined with cerebral blood flow (CBF) measurements at preterm birth and had a subsequent history of attention deficit. We found that high dopamine receptor availability ('empty receptors') was linked with increased RT and RT variability, supporting the concept of a dopaminergic role in symptomatology. High dopamine receptor availability was predicted by low neonatal CBF, supporting the hypothesis of cerebral ischaemia as a contributing factor in infants susceptible to ADHD.

Adolescent↗
PubMed2004

[Christian Bohr and the Seven Little Devils].

The author explores novel lessons emerging from the oxygen diffusion controversy between Christian Bohr on one side and August and Marie Krogh on the other. THe controversy found its emphatic expression in August and Marie Krogh's "Seven Little Devils", a series of papers published back-to-back in the 1910 volume of Skandinavisches Archiv für Physiologie. The Devils unjustifiably sealed the fate of Christian Bohr's theory of active cellular participation in the transport of oxygen from the lungs to the pulmonary circulation. The author's renewed examination of the original papers of Bohr and the Kroghs reveals that Bohr's concept of active cellular participation in diffusion is entirely compatible with the mechanism of capillary recruitment, for the discovery of which Krogh was later awarded Nobel's Prize, years after Bohr's untimely and unexpected death in 1911.

History, 20th Century↗
PubMed2003

The Danish PET/depression project: poor verbal fluency performance despite normal prefrontal activation in patients with major depression.

The verbal fluency (VF) test is associated with prefrontal and cingulate functioning. We used positron emission tomography (PET) to test the hypothesis that inactivity in these regions can explain why patients with depression often perform poorly on this test. Forty-one patients with major depression and 46 controls were scanned during rest and during activation with the VF test. The differences between the two conditions were mapped for each of the two groups, and between-group differences in the activation pattern were calculated on a voxel-by-voxel basis. As predicted, the patients performed significantly more poorly on the test. In both groups activations were seen in the left anterior cingulate region, the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the right cerebellum. Performance was correlated to the cerebral perfusion in to the left occipitotemporal gyrus and the left cerebellum. However, no difference in activation between the two groups was significant. The present study had sufficient power to detect potential differences between the two groups, and the subtraction tasks were appropriate. Therefore, the result supports the notion that abnormalities in the prefrontal cortex in depression are qualitative in nature rather than quantitative; this suggests depression involves dys-coordination of neural activity in the frontal lobes rather than a simple reduction in activity.

Adult↗
PubMed2003

Kinetics of the uptake and distribution of the dopamine D(2,3) agonist (R)-N-[1-(11)C]n-propylnorapomorphine in brain of healthy and MPTP-treated Göttingen miniature pigs.

The binding of radioligand agonists to dopamine receptors in living brain can be informative about the abundance of receptors which are coupled to intracellular second messenger systems. Therefore, we developed a radiosynthesis for the dopamine D(2,3) partial agonist (R)-N- [1-(11)C]n-propylnorapomorphine ([(11)C]NPA). The uptake of this tracer in brain of anesthetized Göttingen miniature pigs was recorded by positron emission tomography (PET) and analyzed by compartmental analysis using the metabolite-corrected arterial input, and using reference tissue methods. [(11)C]NPA had a blood-brain unidirectional clearance of approximately 0.35 ml g(-1) min(-1) and an apparent distribution volume of 6 ml g(-1) in cerebellum. The ligand had a binding potential of 1.5 in striatum, comparable to that reported previously for the receptor antagonist [(11)C]raclopride in the same strain of animals. Significant binding was detected in the hypophysis, thalamus, and medial forebrain bundle. The binding in striatum was of comparable magnitude in normal pigs and in pigs with a documented 50% dopamine depletion produced by MPTP-intoxication. Deep brain stimulation of the subthalamus was without conspicuous effect on the binding of [(11)C]NPA in vivo. Results of this preliminary study indicate that this tracer meets many requirements for assaying dopamine agonist binding sites by PET.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Emotional valence modulates activity in the posterior fusiform gyrus and inferior medial prefrontal cortex in social perception.

Previous studies have shown that during the presentation of emotionally loaded visual stimuli, activity increases in the visual and limbic cortices. This study focuses on empathic reactions induced by presenting pictures of situations and facial expressions from a "third party" point of view only. We measured regional changes in blood flow (rCBF) in nine healthy subjects while they were looking at neutral, positive, or negative emotional pictures of low (facial expressions) and high (persons in real-life situations) social complexity. A significant rCBF increase occurred in the right posterior fusiform gyrus during presentation of emotional pictures of both low and high social complexity. We also observed an interaction between emotionality and social complexity in the left inferior occipital gyrus for situations, where emotionality produced a significantly larger rCBF increase for situations than faces. No significant rCBF changes were observed in the amygdala or other parts of the limbic system. A significant rCBF decrease was found in the right inferior medial prefrontal cortex during presentation of the emotional pictures. This is discussed with respect to the "default mode of the brain" theory. We suggest that there is a neural network in the posterior fusiform and inferior occipital gyrus specialized in identifying emotionally important visual clues. Messages from this and other areas converge to the medial prefrontal cortex, to be evaluated in terms of relevance for attention. We believe that this is a crucial part of a network used in normal empathic reactions and social interactions.

Adult↗
PubMed2003

Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain.

Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [(11)C]raclopride to dopamine D(2,3) receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [(11)C]raclopride for dopamine D(2,3) receptors. However, the sensitivity of [(11)C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [(11)C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [(15)O]water. Neither a low dose of nicotine (50 mu kg(-1), iv) nor a high dose of nicotine (500 microg kg(-1), iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [(11)C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [(11)C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition between endogenous dopamine for [(11)C]raclopride binding sites with a complex temporal and spacial pattern in pig brain, initially presenting in the left ventral striatum.

Animals↗
PubMed2003

Separate neural pathways for contour and biological-motion cues in motion-defined animal shapes.

To determine whether contour and biological motion (BM) cues for motion-defined shapes are subserved by two separate mechanisms, we used PET to measure regional cerebral blood flow in nine human subjects. Subjects were scanned in the following four conditions: (1) contour-defined animals with natural movements (running), (2) motion-defined animals in which the contours were removed and dots were placed on the limbs and moving parts (BM; running); (3) drifting static animal shapes (contours); and (4) drifting dots. The results demonstrate that the perception of BM involves the superior frontal gyrus, the precuneus, the fusiform, the lingual and the medial temporal gyri, the inferior parietal lobe, the hippocampal and parahippocampal areas, and the cerebellum. In addition, the anterior cingulate cortex and the amygdala were significantly activated. The perception of contour-defined shapes produced significant elevation of rCBF in some areas similar to the BM condition, namely the fusiform, medial occipital, medial temporal, and lingual gyri. Only the occipital pole and the inferior temporal cortex were specifically activated by contour-defined shapes. These results are congruent with previous findings that the dorsal visual pathway is important for the perception of BM. They further support psychophysical results showing that contour and BM cues for motion-defined animal shapes are processed by independent channels.

Adult↗
PubMed2003

Minipig negative slow wave demonstrates target/nontarget differences in P300 paradigm.

The negative slow wave (NSW) is a late component of the event-related potential (ERP) in man modulated like the P300 by the stimulus, the task, and the response demand. Aiming at the development of a minipig model of schizophrenia, we investigated scalp ERPs in an auditory P300 paradigm in six Göttingen minipigs. Before training, we observed no difference between target and nontarget NSW. After training, target NSW amplitude was increased 50% compared to nontarget. A P350 was recognized, but the finding of a lack of target/nontarget difference is not conclusive.

Acoustic Stimulation↗
PubMed2003

Speech activation of language dominant hemisphere: a single-photon emission computed tomography study.

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.

Adolescent↗