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Biomedical subjects

Albert Gjedde

Publications and source records attributed to Albert Gjedde.

At least 19 recordsLinked to original sources
PubMed2006

Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans.

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.

Adult↗
PubMed2006

Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving.

In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [(11)C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.

Adult↗
PubMed2006

Stimulation of subthalamic nucleus inhibits emotional activation of fusiform gyrus.

In patients with Parkinson's disease, deep brain stimulation of the subthalamic nucleus is known to impair their ability to correctly identify facial expressions of negative emotions. This difficulty exists only when the stimulator is active. The reason for the impairment is unknown. To test the hypothesis that the stimulation itself is responsible, we used positron emission tomography to compare functional activations of brain regions in nine patients with Parkinson's disease treated with surgically implanted electrodes into both subthalamic nuclei, and 22 healthy volunteers. Both groups viewed images with neutral or emotional content from Aarhus University's standard Empathy Picture System () with 360 images of people in pleasant, unpleasant or neutral real-life situations, presenting either the situations or close-ups of the facial expressions of the people involved. Both groups, the patients with stimulation OFF and the healthy volunteers, had raised regional blood flow rates (rCBF) in the right fusiform gyrus when they viewed emotionally expressive faces compared to neutral faces. With stimulation turned on, this response was significantly inhibited in the patients because of a raised rCBF at baseline during the neutral faces. Stimulation of the STN did not alter fusiform reaction to emotionally pregnant scenes; nor did healthy volunteers and patients react differently to these stimuli regardless of stimulation status. Also, STN stimulation raised the emotional activation of the anterior cingulate and lowered the activity of the putamen. The findings suggest that the stimulation of the subthalamic nucleus interferes with the integration of specific neocortical networks involved in the recognition of facial expressions.

Adult↗
PubMed2006

Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects.

After loss of a particular sensory channel, the deprived cortex can be activated by inputs from other sensory modalities. It is not known whether activation of the rewired cortex evokes subjective experiences characteristic of that cortex or consistent with the rerouted sensory information. In a previous study, blind subjects were trained to perform visual tasks with a tongue display unit, a sensory substitution device that translates visual displays into electrotactile tongue stimulation. This cross-modal sensory stimulation activated their visual cortices. We now extend this finding by using transcranial magnetic stimulation to examine the perceptual correlates of training-induced plastic responses. We find that blind subjects proficient with the use of the tongue display unit report somatopically organized tactile sensations that are referred to the tongue when transcranial magnetic stimulation is applied over the occipital cortex. No such sensations were evoked in trained, blindfolded, seeing control subjects who performed the sensory substitution task equally well. These data show that the perceptual correlate of activity in a given cortical area reflects the characteristics of its novel sensory input source.

Adult↗
PubMed2006

Restored speech comprehension linked to activity in left inferior prefrontal and right temporal cortices in postlingual deafness.

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.

Adult↗
PubMed2006

Neuronal-glial glucose oxidation and glutamatergic-GABAergic function.

Prior 13C magnetic resonance spectroscopy (MRS) experiments, which simultaneously measured in vivo rates of total glutamate-glutamine cycling (V(cyc(tot))) and neuronal glucose oxidation (CMR(glc(ox), N)), revealed a linear relationship between these fluxes above isoelectricity, with a slope of approximately 1. In vitro glial culture studies examining glutamate uptake indicated that glutamate, which is cotransported with Na+, stimulated glial uptake of glucose and release of lactate. These in vivo and in vitro results were consolidated into a model: recycling of one molecule of neurotransmitter between glia and neurons was associated with oxidation of one glucose molecule in neurons; however, the glucose was taken up only by glia and all the lactate (pyruvate) generated by glial glycolysis was transferred to neurons for oxidation. The model was consistent with the 1:1 relationship between DeltaCMR(glc(ox), N) and DeltaV(cyc(tot)) measured by 13C MRS. However, the model could not specify the energetics of glia and gamma-amino butyric acid (GABA) neurons because quantitative values for these pathways were not available. Here, we review recent 13C and 14C tracer studies that enable us to include these fluxes in a more comprehensive model. The revised model shows that glia produce at least 8% of total oxidative ATP and GABAergic neurons generate approximately 18% of total oxidative ATP in neurons. Neurons produce at least 88% of total oxidative ATP, and take up approximately 26% of the total glucose oxidized. Glial lactate (pyruvate) still makes the major contribution to neuronal oxidation, but approximately 30% less than predicted by the prior model. The relationship observed between DeltaCMR(glc(ox), N) and DeltaV(cyc(tot)) is determined by glial glycolytic ATP as before. Quantitative aspects of the model, which can be tested by experimentation, are discussed.

Animals↗
PubMed2006

Dopamine storage capacity in caudate and putamen of patients with early Parkinson's disease: correlation with asymmetry of motor symptoms.

Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [(18)F]fluorodopa (FDOPA) assumes irreversible trapping of [(18)F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [(18)F]fluorodopamine from the brain (k(loss)), from which can be calculated an effective distribution volume (EDV(1)), which is an index of [(18)F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k(loss) and EDV, here defined as EDV(2). This method is based on subtraction of the calculated brain concentrations of the FDOPA metabolite O-methyl-FDOPA, rather than the subtraction of the entire radioactivity in a reference region. We now extend this method for the parametric mapping of these parameters in the brain of healthy aged volunteers and patients with Parkinson's disease (PD), with asymmetry of motor symptoms. For parametric mapping, we use a novel application of a multilinear solution for the two-tissue compartment FDOPA model. We also test a new application of the Logan graphical analysis for mapping of the FDOPA distribution volume at equilibrium. The estimates of k(loss) and EDV(2) were more sensitive for the discrimination of biochemical abnormality in the putamen of patients with early PD relative to healthy aged subjects, than was the conventional net influx estimate. Of the several methods, multilinear estimates of EDV(2) were most sensitive for discrimination of PD and normal putamen. However, k(loss) was most sensitive for detecting biochemical asymmetry in the putamen of PD patients, and only k(loss) also detected in the caudate of PD patients a decline in the retention of [(18)F]fluorodopamine relative to healthy aged control subjects.

Aged↗
PubMed2005

Behavioral response to novelty correlates with dopamine receptor availability in striatum of Göttingen minipigs.

Behavioral response to novelty in rats has been linked both to dopamine transmission in the ventral striatum, and to propensity to self-administer psychostimulant drugs. In order to probe the relationship between behavioral response to novelty and dopamine systems we have developed a behavioral model for correlation with positron emission tomography (PET) of dopamine transmission in brain of Göttingen minipigs. In the present study, we measured exploration of a novel object by recording the number of contacts, and duration of contact with a novel object, in groups of six male and six female adult minipigs. We hypothesized that these novelty scores would correlate with the amphetamine-evoked dopamine release in ventral striatum, measured 2 weeks later in a PET study of the availability of binding sites for the dopamine D2/3 antagonist [11C]raclopride. There were significant correlations between duration of contact with a novel object and the amphetamine-evoked reductions in binding potential (DeltapB) in the left ventral striatum of the 12 animals; Comparison of results by gender revealed that the correlation was driven mainly by the male group, and was not present in the female group. We interpret these results to show that propensity to explore an unfamiliar object is relatively elevated in pigs with low basal occupancy of dopamine D2/3 receptors by endogenous dopamine, and with high amphetamine-induced occupancy of released dopamine in the male pigs.

Adaptation, Psychological↗
PubMed2005

Cortical responses to promontorial stimulation in postlingual deafness.

Electrical stimulation with a transtympanic electrode on the promontory of the middle ear allows the tasks of gap detection and temporal difference limen (TDL) to be carried out by both normally hearing and deaf subjects. Previous neuroimaging of normally hearing subjects revealed a region in the right posterior temporal lobe that is crucial to duration discrimination. The present study tested the hypothesis that postlingually deaf subjects recruit this area when they make subtle temporal discriminations. Fourteen postlingually deaf adult cochlear implant candidates were stimulated in the ear chosen for implantation. Altered cerebral activity was recorded with positron emission tomography as incremental 15-O-labelled water uptake. On stimulation with tone bursts, we found bilateral activity close to the primary auditory cortex in all subjects. However, subjects performing well on the TDL task demonstrated right-lateralized fronto-temporal and left-lateralized temporal activity in the respective TDL and gap-detection tasks, while subjects who failed to detect duration differences of less than 200 ms in the TDL discrimination task only had frontal and occipital rather than temporal lobe activation. We conclude that the ability to involve the right posterior temporal region is important to duration discrimination. This ability can be evaluated pre-operatively.

Acoustic Stimulation↗
PubMed2005

Pattern-motion selectivity in the human pulvinar.

On the basis of anatomical and physiological data obtained on animal models, we recently proposed that neurons in the main visual extrageniculate nuclei complex, the pulvinar, are actively involved in higher-order visual processing. Pulvinar neurons have been shown to integrate the component signals of a plaid pattern into a coherent global percept (pattern-motion selectivity). Using positron emission tomography (PET), we have investigated the possibility that the human pulvinar is also involved in plaid-defined higher-order motion integration. Plaid patterns were presented to normal observers in two conditions (coherent vs. transparent) created by varying the relative spatial frequency of the two gratings comprising the plaid. Regions of interest analysis revealed a significant activation of the pulvinar in the coherent condition supporting the notion that the human pulvinar nucleus is involved in higher-order motion processing. Plaid pattern activation was also observed in the medial temporal gyrus (area MT/V5), a motion area with strong anatomical connections to the pulvinar. These data provide the first direct evidence that the human pulvinar is involved in complex motion integration, as previously shown in animal models, and further support the existence of cortico-thalamo-cortical computational networks involved in higher-order visual processing.

Adult↗
PubMed2005

Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder.

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.

Adolescent↗
PubMed2005

Mapping the amphetamine-evoked dopamine release in the brain of the Göttingen minipig.

The availability of dopamine D(2/3) binding sites in brain of six male and six female Göttingen minipigs was measured in a baseline condition and after challenge with amphetamine sulfate (1mg/kg, i.v.) in PET studies with [(11)C]raclopride. Maps of the binding potential (pB; B(max)/K(d)) of [(11)C]raclopride were spatially normalized and co-registered to a common stereotaxic coordinate system for pig brain. The pB maps were then analyzed by volume of interest and voxel-wise comparisons of gender and condition. The mean baseline pB tended to be 10-20% higher in striatum of the female group, but this gender difference was not significant. Variance of the mean baseline pB was higher in the males (44%) than in females (30%), but there was no correlation between pB and individual plasma cortisol or testosterone concentrations. Using statistical parametric mapping, we detected a focus in the right posterior putamen where the magnitude of the amphetamine-evoked decrease in pB was greater in the male than in the female group. Thus, the spatial pattern of reactivity of dopamine D(2/3) receptor availability to amphetamine challenge is not identical in male and female pigs. Within the entire population, the decline in pB evoked by amphetamine (Delta pB) was greater in the ventral striatum (-28%) than in the caudate nucleus (-17%), consistent with earlier reports in monkeys and humans. The magnitude of Delta pB correlated highly with the baseline pB values in all divisions of the striatum. Based upon the principles of competitive binding, the slope of this empirical relationship, f(i), is equal to the fraction of [(11)C]raclopride binding sites sensitive to endogenous dopamine; the magnitude of this fraction ranged from 0.29 in the caudate to 0.36 in the ventral striatum.

Amphetamine↗
PubMed2005

To musicians, the message is in the meter pre-attentive neuronal responses to incongruent rhythm are left-lateralized in musicians.

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.

Acoustic Stimulation↗
PubMed2005

Cross-modal plasticity revealed by electrotactile stimulation of the tongue in the congenitally blind.

In sensory substitution, information acquired with one sensory modality is used to accomplish a task which is normally subserved primarily by another sensory modality. We used PET to study cross-modal plasticity in the congenitally blind, using electrotactile stimulation of the tongue. Blind (n = 6) and sighted blindfolded controls (n = 5) were scanned before and after they were trained to use their tongue in a Snellen orientation detection task. Results showed that both groups of subjects learned the discrimination orientation task after seven 1 h training sessions. Before training, no significant changes in regional cerebral blood flow (rCBF) were observed in the occipital cortex in either group. In sharp contrast, activity in the occipital cortex increased after practice for the blind, but not for the sighted, providing evidence for training-induced plasticity in the blind. An inter-regional correlation analysis showed that task-related rCBF changes in left posterior parietal cortex were positively correlated with rCBF changes in the occipital area of the trained blind. These data reveal that cross-modal plasticity in the blind develops rapidly and that the occipital cortex is part of a functional neural network for tactile discrimination in conjunction with the posterior parietal cortex. Our data further show that the tongue can act as a portal to convey somatosensory information to visual cortex.

Adult↗
PubMed2005

The pathways of oxygen in brain. I. Delivery and metabolism of oxygen.

Flow-metabolism coupling in brain is different from flow-metabolism coupling in other vascular beds. In the classic description of Krogh, the capillary bed is a system of parallel tubes serving cylinders of tissue known as Krogh's cylinders. This simple arrangement yielded a quantitative expression of oxygen delivery to the tissue. However, in brain tissue, the arrangement is so disorderly that no prediction of oxygen tensions in the tissue is possible. Only two claims of the capillary bed in the brain appear to be indisputable, i.e., the capillaries have a common arterial source and a common venous terminus, and their density is proportional to the average regional rates of metabolism at steady-state. The following revision of the mechanism of flow-metabolism coupling in brain arose from the simple assumption, first introduced by Erwin R. Weibel in The Pathway for Oxygen, that every segment of the capillary bed "feeds" the same amount of brain tissue, i.e., that every fraction of the tissue is served by commensurate fractions of capillary density and oxygen diffusibility and accounts for the same fraction of the total oxygen consumption.

Brain↗
PubMed2005

The pathways of oxygen in brain. II. Competitions for cytochrome c oxidase and NOS are keys to flow-metabolism coupling.

It has been well-known for many years that cerebral oxygen consumption remains constant during moderate changes of blood flow, as measured during hypo- or hypercapnia or indomethacin administration. Current models of flow-metabolism coupling link blood-brain transfer of oxygen to oxygen metabolism in mitochondria. The resulting quantitative relations between flow and metabolism reveal that a close link between diffusion and metabolism prevents the enzyme from maintaining a constant oxygen consumption when blood flow changes, unless the enzyme's affinity towards oxygen is adjusted commensurately.

Brain↗
PubMed2005

Use of time differences in normal hearing--cortical processing of promontorial stimuli.

To test the hypothesis that ability to discriminate small duration differences is positively correlated with activity in the right temporal lobe, we used positron emission tomography in six normally hearing subjects, stimulated via the promontory in a procedure that mimics the auditory nerve stimulation with a cochlear implant. Stimulus consisted of electrical bursts, and tasks included gap detection and temporal difference limen (TDL). TDL is a measure of discriminatory processing of sound duration in cochlear implant candidates, demonstrated to predict outcome. Good speech perception after cochlear implantation is associated with activity in right temporal areas. Although perceived variably by the subjects, the stimulus itself activated bilateral secondary somatosensory cortex, suggesting differential stimulation of multiple sensory modalities. Only TDL raised blood flow in both posterior middle temporal gyri (MTG) and the right prefrontal cortex. As the right posterior MTG is known to be active during duration discrimination of different modalities and in the perception of words containing manipulated phonemes, we conclude that recruitment of this part of the right hemisphere is important to the comprehension of speech containing mostly temporal cues. The study shows that stimulus-induced activation reflects the goal of the task rather than the nature of the stimulus.

Adult↗