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Albert Gjedde
  • 673 Silkeborgvej
    DK-8220 Brabrand, Denmark
  • +45 29177601
  • Neuroscientist with experience from work and positions in Denmark, EU, USA, Canada, South Africa, and other countries... moreedit
RationalThe immediate social context significantly influences alcohol consumption in humans. Recent studies have revealed that peer presence could modulate drugs use in rats. The most efficient condition to reduce cocaine intake is the... more
RationalThe immediate social context significantly influences alcohol consumption in humans. Recent studies have revealed that peer presence could modulate drugs use in rats. The most efficient condition to reduce cocaine intake is the presence of a stranger peer, naive to drugs. Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN), which was shown to have beneficial effects on addiction to cocaine or alcohol, also modulate the protective influence of peer’s presence on cocaine use.ObjectivesThis study aimed to: 1) explore how the presence of an alcohol-naive stranger peer affects recreational and escalated alcohol intake, and 2) assess the involvement of STN on alcohol use and in the modulation induced by the presence of an alcohol-naïve stranger peer.MethodsRats with STN DBS and control animals self-administered 10% (v/v) ethanol in presence, or absence, of an alcohol-naive stranger peer, before and after escalation of ethanol intake (observed after intermittent alcohol (...
Objective: We investigated the association between peripheral insulin resistance (IR) and brain glucose uptake (BGU) and further determined if testing condition (fasting vs. hyperinsulinemic-euglycemic clamp) was a moderator of the... more
Objective: We investigated the association between peripheral insulin resistance (IR) and brain glucose uptake (BGU) and further determined if testing condition (fasting vs. hyperinsulinemic-euglycemic clamp) was a moderator of the association. Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science, studies assessing an association between measures of or clinical proxies for IR (e.g. diabetes and obesity) and BGU were included. Effect sizes were standardized and transformed into correlation coefficients and a random effect meta-analysis performed. Further, a subgroup analysis on testing condition was conducted. Results: Twenty-one studies (n = 3,620) were included in the meta-analysis. The pooled correlation (-0.13 [95% CI: -0.37; 0.12], p=0.3) showed a substantial heterogeneity (I2 = 98%). Subgroup analysis revealed that IR negatively correlated with BGU when subjects were examined at fasting conditions (-0.42 [95% CI: -0.59; -0.21], I2 =...
aDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark bDepartment of Neuroscience, University of Copenhagen, Copenhagen, Denmark cDepartment of Neurology and Neurosurgery, McGill University, Montreal, QC,... more
aDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark bDepartment of Neuroscience, University of Copenhagen, Copenhagen, Denmark cDepartment of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada dDepartment of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States eNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the... more
Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting brain hypoxia could help us understand brain diseases associated with hypoxia. A total of 65 subjects participated in this study: 30 subjects were exposed to poikilocapnic hypoxia, 14 were exposed to isocapnic hypoxia, and 21 were exposed to carbon monoxide (CO). Using this setup, we examined whether lactate production reacts to an overall reduction in arterial oxygen concentration or solely to reduced arterial oxygen partial pressure. We measured cerebral blood flow (CBF), CMRO2, and lactate concentrations by magnetic resonance imaging and spectroscopy. CBF increased (P < 10−4), whereas the CMRO2 remained unaffected (P > 0.076) in a...
With the advent of neuroreceptor and neurotransmission imaging by means of positron emission tomography and single-photon emission computed tomography in vivo, it is now possible to directly record the normal and pathophysiological... more
With the advent of neuroreceptor and neurotransmission imaging by means of positron emission tomography and single-photon emission computed tomography in vivo, it is now possible to directly record the normal and pathophysiological processes served by monoamines in the brain, as well as to examine the possibilities and potential impact of treatment of disorders of monoaminergic neurotransmission. This article describes the methods of noninvasive brain imaging and the benefits that this imaging can bring to the understanding of disturbed monoaminergic neurotransmission, the mechanisms underlying the disturbances, and the impact of possible therapies.
The first purpose of this study was to quantify human intrasynaptic/extracellular dopamine release following cocaine and amphetamine. The results in 11 cocaine users, 5 controls, and 4 schizophrenic patients are reported. The second... more
The first purpose of this study was to quantify human intrasynaptic/extracellular dopamine release following cocaine and amphetamine. The results in 11 cocaine users, 5 controls, and 4 schizophrenic patients are reported. The second purpose of this study is to illustrate a new technique to quantify dopamine receptor density and neurotransmitter release. The method allows the calculation of an absolute receptor density (Bmax) and an estimation of the dopamine bound to the receptor. The method was applied to normal volunteers and patients with schizophrenia in a four positron emission tomography scan paradigm. The steps for the quantification are outlined in this presentation and are generalizable to other radioligands and neurotransmitter systems.
Measurement of the regional cerebral blood flow (rCBF) is an important parameter in the evaluation of cerebral function. With positron emission tomography (PET) rCBF has predominantly been quantified using the short-lived radiotracer... more
Measurement of the regional cerebral blood flow (rCBF) is an important parameter in the evaluation of cerebral function. With positron emission tomography (PET) rCBF has predominantly been quantified using the short-lived radiotracer oxygen-15 labelled water (H 2 15 O) and an adaptation of the Kety one-tissue compartment autoradiographic model. The values attained in putative grey matter, however, are systematically underestimated because of the limited scanner resolution. For this reason we applied a dynamic kinetic two-tissue compartment model including a fast and a slow flow component each with a perfusable tissue fraction. In the fast component rCBF was 2-2.5 times greater than grey matter values using traditional autoradiography in both human and monkey. Visual stimulation in human gave a corrected rCBF increase of approximately 40%. Visual stimulation was also used to indirectly validate carbon-10 labelled carbondioxide ( 10 CO 2 ), a new very short-lived rCBF PET tracer with ...
We investigated neuromagnetic responses during an auditorily paced synchronization task using a 122-channel whole-head neuromagnetometer. Eight healthy right handed subjects were asked to synchronize left and right unilateral finger taps... more
We investigated neuromagnetic responses during an auditorily paced synchronization task using a 122-channel whole-head neuromagnetometer. Eight healthy right handed subjects were asked to synchronize left and right unilateral finger taps to a regular binaural pacing signal. Synchronization of the right hand with an auditory pacing signal is known to be associated with three tap-related neuromagnetic sources localized in the contralateral primary sensorimotor cortex. While the first source represents the neuromagnetic correlate of the motor command the second one reflects somatosensory feedback due to the finger movement. The functional meaning of the third source, which is also localized in the primary somatosensory cortex is still unclear. On the one hand this source represents a neuromagnetic correlate of somatosensory feedback due to the finger tap. On the other hand it has been suggested that the function of this source could additionally represent a cognitive process, which enables the subject to monitor the time distance between taps and clicks. The aim of the present study was to elucidate the function of this source, which would fundamentally reform the meaning of the primary somatosensory cortex in the timing of movements with respect to external events. The data of the present study demonstrate that the three sources in the contralateral sensorimotor cortex are stronger related to the tap than to the click. This result contradicts the assumption of a cognitive process localized in the primary somatosensory cortex. Thus, activation in the primary somatosensory cortex most likely represents exclusively somatosensory feedback and no further cognitive processes.
Astrocyte end‐feet surround intraparenchymal microvessels and represent therefore the first cellular barrier for glucose entering the brain. As such, they are a likely site of prevalent glucose uptake. Astrocytic processes are also... more
Astrocyte end‐feet surround intraparenchymal microvessels and represent therefore the first cellular barrier for glucose entering the brain. As such, they are a likely site of prevalent glucose uptake. Astrocytic processes are also wrapped around synaptic contacts, implying that they are ideally positioned to sense and be functionally coupled to increased synaptic activity. We have recently demonstrated that glutamate, the main excitatory neurotransmitter, stimulates in a concentration‐dependent manner 2‐DG uptake and phosphorylation by astrocytes in primary culture.1 The effect is not receptor‐mediated but rather proceeds via one of the recently cloned glutamate transporter. The mechanism involves an activation of the Na+/K+ ATPase. Concomitant to the stimulation of glucose uptake, glutamate causes a concentration‐dependent increase in lactate efflux. These observations suggest that glutamate uptake is coupled to aerobic glycolysis in astrocytes. In addition, since glutamate releas...
The poor spatial resolution of positron emission tomography (PET) is a limiting factor in the accurate assay of physiological processes investigated by compartmental modeling of tracer uptake and metabolism in living human brain. The... more
The poor spatial resolution of positron emission tomography (PET) is a limiting factor in the accurate assay of physiological processes investigated by compartmental modeling of tracer uptake and metabolism in living human brain. The radioactivity concentration in a region-of-interest is consequently altered by loss of signal from that structure and contamination from adjacent brain regions, phenomena known as partial volume effects. We now apply an MRI-based algorithm to compensate for partial volume effects in the special case of compartmental modeling of the cerebral uptake of 6-[(18)F]fluoro-L-dopa (FDOPA), an exogenous substrate of dopa decarboxylase. High-resolution MRI scans were obtained from normal volunteers (n = 4) and patients with Parkinson's disease (n = 4) in order to segment specific brain regions and calculate the partial volume correction factors. Dynamic 2D PET scans were acquired during 90 min following intravenous infusion of FDOPA. After partial volume correction, the apparent net blood-brain clearance of FDOPA (K(i)) was greatly increased in caudate and putamen of normal subjects and in caudate of Parkinson's disease patients. The equilibrium distribution volume of FDOPA (V(D)(e)) in cerebral cortex increased by 35% in all subjects. Using a two-compartment model, the relative activity of dopa decarboxylase with respect to FDOPA (k(D)(3)) in the basal ganglia was increased 2-3 times in normal subjects, to the range obtained previously in brain of living rat. The partial volume correction also increased the magnitude of k(D)(3) in caudate of Parkinson's disease patients, but did not alter k(D)(3) in putamen. A three-compartment model correcting for elimination of decarboxylated metabolites also yielded higher estimates of k(D)(3), but with a penalty in precision of the estimates. Together, these observations suggest that the limited spatial resolution of PET results in substantial underestimation of the true rate of FDOPA uptake and metabolism in vivo, and may also tend to obscure regional heterogeneity in the neurochemical pathology of Parkinson's disease.
Two radioligands specific for the dopamine system were used to study the influence of correction for partial volume effects on quantitative binding data obtained from positron emission tomography from various brain regions.... more
Two radioligands specific for the dopamine system were used to study the influence of correction for partial volume effects on quantitative binding data obtained from positron emission tomography from various brain regions. [11C]Raclopride binds to the dopamine D2 and D3 receptors, and [11C]WIN 35,428 binds to the dopamine transporter. Both are highly concentrated in the basal ganglia but not in the cerebellum. Normal subjects and patients with Lesch-Nyhan syndrome, a disease in which brain atrophy occurs, were studied before and after correction for the partial volume effect. A dramatic elevation in rate constants, especially the k3/k4 ratio, was observed after correction in both normal subjects and patients. The patients, who initially had a decrease in [11C]WIN 35,428 binding at the dopamine transporter site compared to normal subjects, retained this separation after the correction algorithm was applied.
Any books that you read, no matter how you got the sentences that have been read from the books, surely they will give you goodness. But, we will show you one of recommendation of the book that you need to read. This quantitative... more
Any books that you read, no matter how you got the sentences that have been read from the books, surely they will give you goodness. But, we will show you one of recommendation of the book that you need to read. This quantitative functional brain imaging with positron emission tomography is what we surely mean. We will show you the reasonable reasons why you need to read this book. This book is a kind of precious book written by an experienced author.
INTRODUCTION Stress is one of the greatest burdens of our society and often implies impairments in cognitive and emotional functions. Here, we hypothesise that changes in the brain's dopamine (DA)-based mesocorticolimbic projec-tions... more
INTRODUCTION Stress is one of the greatest burdens of our society and often implies impairments in cognitive and emotional functions. Here, we hypothesise that changes in the brain's dopamine (DA)-based mesocorticolimbic projec-tions in patients with work-related stress (adjustment disorder) will manifest themselves as altered glucose metabolism in relation to neural activity, and as altered DA radiotracer binding potentials at the relevant receptors. METHODS Subjects and healthy controls undergo neuropsychiatric tests and PET/MRI with three tracers: 18F-fluorodeoxyglucose to measure glucose metabolism as a marker of neural activity, 11C-raclopride to explore binding potentials in the striatum, and 11C-FLB 457 to study possibly impaired mesocortical dopaminergic transmission in the cortex. To demonstrate differences of glucose metabolism, more than 2 × 41 patients/controls are needed. We expect to find that symptoms of cognitive and motivational reward deficits are attributable ...
Transcranial photoacoustic (PA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of functional neuroimaging. The technique previously distinguished global seizure activity from control... more
Transcranial photoacoustic (PA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of functional neuroimaging. The technique previously distinguished global seizure activity from control neural activity in groups of rats. To validate the focal specificity of transcranial PA with VSD (IR780) imaging in vivo, we now present proofs-of-concept that the results differentiate between N-methyl-D-aspartate (NMDA) evoked neural activities in two distinct circuits with differential response profiles, i.e., sensorimotor cortex and hippocampus. Concurrent quantitative EEG (qEEG) recorded real time circuit dynamics. We hypothesized that NMDA evoked focal glutamate release in both circuits would correlate with increases of location-specific PA signals and time-specific EEG signals. To test the hypothesis in hippocampus 0.3, 1 and 3 mM NMDA was infused at a rate of 2 μl/min over 60 min via an implanted microdialysis probe. The dialysate samples collec...
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This chapter evaluates the external dispersion characteristics of an automatic blood sampling system (ABSS). It was done by comparing the manually sampled blood curve at the level of the radial artery, proximal to the ABSS, Ca(t), with... more
This chapter evaluates the external dispersion characteristics of an automatic blood sampling system (ABSS). It was done by comparing the manually sampled blood curve at the level of the radial artery, proximal to the ABSS, Ca(t), with that measured by the ABSS, g(t) , using data from cerebral blood flow and oxygen metabolic studies. The tracers, were H 2 15 O, and 15 O-O 2 . Further, the distortion of the blood radioactivity curve brought about by the ABSS is characterized by the means of a dispersion function that was different for each of the two tracers, whereas, at a fixed blood withdrawal rate, a single external tracer delay was measured. The chapter suggests that the difference in the external dispersion characteristics of the two tracers is related to the fact that, for H 2 15 O, the label is approximately uniformly distributed between the plasma and the RBC phases of the blood whereas for 15 O-O 2 , it is restricted to the RBC fraction.

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