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Biomedical subjects

L Friberg

Publications and source records attributed to L Friberg.

At least 19 recordsLinked to original sources
PubMed1999

A 15O-H2O PET study of meditation and the resting state of normal consciousness.

The aim of the present study was to examine whether the neural structures subserving meditation can be reproducibly measured, and, if so, whether they are different from those supporting the resting state of normal consciousness. Cerebral blood flow distribution was investigated with the 15O-H20 PET technique in nine young adults, who were highly experienced yoga teachers, during the relaxation meditation (Yoga Nidra), and during the resting state of normal consciousness. In addition, global CBF was measured in two of the subjects. Spectral EEG analysis was performed throughout the investigations. In meditation, differential activity was seen, with the noticeable exception of V1, in the posterior sensory and associative cortices known to participate in imagery tasks. In the resting state of normal consciousness (compared with meditation as a baseline), differential activity was found in dorso-lateral and orbital frontal cortex, anterior cingulate gyri, left temporal gyri, left inferior parietal lobule, striatal and thalamic regions, pons and cerebellar vermis and hemispheres, structures thought to support an executive attentional network. The mean global flow remained unchanged for both subjects throughout the investigation (39+/-5 and 38+/-4 ml/100 g/min, uncorrected for partial volume effects). It is concluded that the (H2)15O PET method may measure CBF distribution in the meditative state as well as during the resting state of normal consciousness, and that characteristic patterns of neural activity support each state. These findings enhance our understanding of the neural basis of different aspects of consciousness.

Adult↗
PubMed1998

Regulation of nicotinic receptor subtypes following chronic nicotinic agonist exposure in M10 and SH-SY5Y neuroblastoma cells.

The present study further investigated whether nicotinic acetylcholine receptor (nAChR) subtypes differ in their ability to up-regulate following chronic exposure to nicotinic agonists. Seven nicotinic agonists were studied for their ability to influence the number of chick alpha4beta2 nAChR binding sites stably transfected in fibroblasts (M10 cells) following 3 days of exposure. The result showed a positive correlation between the Ki values for binding inhibition and EC50 values for agonist-induced alpha4beta2 nAChR up-regulation. The effects of epibatidine and nicotine were further investigated in human neuroblastoma SH-SY5Y cells (expressing alpha3, alpha5, beta2, and beta4 nAChR subunits). Nicotine exhibited a 14 times lower affinity for the nAChRs in SH-SY5Y cells as compared with M10 cells, whereas epibatidine showed similar affinities for the nAChRs expressed in the two cell lines. The nicotine-induced up-regulation of nAChR binding sites in SH-SY5Y cells was shifted to the right by two orders of magnitude as compared with that in M10 cells. The epibatidine-induced up-regulation of nAChR binding sites in SH-SY5Y cells was one-fourth that in M10 cells. The levels of mRNA of the various nAChR subunits were measured following the nicotinic agonist exposure. In summary, the various nAChR subtypes show different properties in their response to chronic stimulation.

Animals↗
PubMed1997

Activation of the insular cortex during dynamic exercise in humans.

1. The insular cortex has been implicated as a region of cortical cardiovascular control, yet its role during exercise remains undefined. The purpose of the present investigation was to determine whether the insular cortex was activated during volitional dynamic exercise and to evaluate further its role as a site for regulation of autonomic activity. 2. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3. Increases in regional cerebral blood flow (rCBF) distribution were determined for each individual using single-photon emission-computed tomography (SPECT) co-registered with magnetic resonance (MR) images to define exact anatomical sites of cerebral activation during each condition. 4. The rCBF significantly increased in the left insula during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling alone. 5. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical stimulation support the role of leg muscle afferent input towards the full activation of leg motor areas.

Adult↗
PubMed1996

Mechanisms regulating regional cerebral activation during dynamic handgrip in humans.

Dynamic hand movement increases regional cerebral blood flow (rCBF) of the contralateral motor sensory cortex (MS1). This increase is eliminated by regional anesthesia of the working arm, indicating the importance of afferent neural input. The purpose of this study was to determine the specific type of afferent input required for this cerebral activation. The rCBF was measured at +5.0 and +9.0 cm above the orbitomeatal (OM) plane in 13 subjects during 1) rest; 2) dynamic left-hand contractions; 3) postcontraction ischemia (metaboreceptor afferents); and 4) biceps brachii tendon vibration (muscle spindles). The rCBF increased only during dynamic hand contraction; contralateral MS1 (OM +9) by 15% to 64 +/- 8.6 ml.100 g-1.min-1 (P < 0.05); supplementary motor area (OM +9) by 11% to 69 +/- 9.8 ml.100 g-1.min-1 (P < 0.05); and there were also bilateral increases at MS2 (OM +5) [by 16% to 64 +/- 8.6 ml.100 g-1.min-1 (P < 0.05)]. These findings suggest that the rCBF increase during dynamic hand contraction does not require neural input from muscle spindles or metabolically sensitive nerve fibers, although the involvement of mechanoreceptors (group III or Ib) cannot be excluded.

Adult↗
PubMed1995

Regional cerebral activation during auditory stimulation in patients with cochlear implants.

OBJECTIVE: To evaluate a possible change in the regional cerebral blood flow (rCBF) in the language-related cortical areas of the brain during stimulation of a cochlear implant. METHODS: The rCBF was measured by single-photon emission tomography and inhalation of Xenon Xe 133, providing information on the regional functional level of the brain. A supplementary single-photon emission tomographic scan was also performed, using technetium Tc 99m hexamethylpropyleneamineoxime as a flow marker. The rCBF was measured during rest (baseline) and during auditory stimulation by presenting white noise and running speech to the ear with the implant. PATIENTS: Five deaf patients who had undergone intracochlear or extracochlear implantation surgery. RESULTS: As in subjects with normal hearing, notable activation was not found in the relevant primary auditory cortex on stimulation with white noise. Two of the patients with implants had an increase in the rCBF in the relevant contralateral hemisphere on stimulation with running speech, but in the other three patients, a notable increase was not detected. This lack of increase in the rCBF on speech stimulation was consistent with the lack of speech recognition experienced by the subjects when using the implant. In one subject, the implant had a beneficial effect on speech understanding that was associated with a significant increase in the cerebral blood flow in the Broca's speech area and Wernicke's second speech area. CONCLUSIONS: Although the results are preliminary, the single-photon emission tomographic technique may be useful when evaluating the function of a cochlear implant. The method may also help select patients and/or ears for cochlear implantation. Four of five patients had functional defects of auditory relevant cortical areas, suggesting that their deafness might be associated with central impairment in addition to their cochlear defects.

Acoustic Stimulation↗
PubMed1995

Selenium concentrations in brain after exposure to methylmercury: relations between the inorganic mercury fraction and selenium.

Three groups of female monkeys (Macaca fascicularis) were exposed to methylmercury (MeHg, p.o. 50 micrograms Hg/kg body wt per day) for 6, 12, or 18 months. One group was exposed to MeHg for 12 months and kept unexposed for 6 months before sacrifice. Another group of three monkeys was exposed to HgCl2 i.v. for 3 months. Total and inorganic mercury concentrations in occipital pole and thalamus were determined by cold vapor atomic absorption spectroscopy. Selenium concentrations were analyzed by hydride generation atomic absorption spectroscopy. The results indicated an association between concentrations of inorganic mercury and selenium in both occipital pole and thalamus in the MeHg-exposed animals. A linear regression model using concentrations of inorganic mercury (nmol/g wet wt) as independent variable, and selenium concentrations (nmol/g wet wt) as the dependent variable showed significant correlations between the variables in both occipital pole and thalamus (r = 0.85 and r = 0.91, P < 0.0001). The intercept of the regression line was slightly lower (about 2 nmol Se/g wet wt) than the selenium concentrations found in control monkeys (about 3 nmol Se/g wet wt). There was a tendency to a "hockey stick"-shaped relationship between concentrations of selenium and inorganic mercury in the thalamus of monkeys with ongoing exposure to MeHg. An important role for selenium in the retention of mercury in brain is indicated.

Animals↗
PubMed1995

In vivo neuroreceptor imaging by SPECT in migraine.

In vivo imaging of neuroreceptor ligand binding in the human brain is a young discipline. In migraine patients only few studies on dopamine D2 receptor binding have been reported. Many potentially useful radiolabeled receptor ligands for SPECT investigations in humans are currently being treated in animal models. There are no reports on development of radiolabeled, specific 5HT1D receptor ligands, which would be of considerable interest in studies of migraine patients. The radiochemistry of receptor ligand development for SPECT is complex and expensive. However, once a suitable radiolabeled ligand has been developed, e.g. labeled with I-123 with a fairly long decay ratio, it can be made widely accessible to nuclear medical units. SPECT might even prove to be as powerful a tool as PET for quantification of neuroreceptor binding profiles. Quantification, though, is not a trivial problem and there is still a need for development of kinetic models that can be applied in the clinical setting, particularly for studies of acute conditions like a migraine attack.

Humans↗
PubMed1994

Speciation of mercury in the primate blood and brain following long-term exposure to methyl mercury.

Total (T-Hg) and inorganic (I-Hg) mercury in blood and brain of female Macaca fascicularis monkeys, exposed to daily peroral doses of methyl mercury (MeHg; 50 micrograms Hg/kg body wt) for 6, 12, or 18 months, or to continuous iv infusion of HgCl2 (200 micrograms Hg/kg body wt) for 3 months, were determined. In normal weight monkeys (2.4-4.1 kg body wt) exposed to MeHg, steady state of T-Hg in blood (1.1 micrograms Hg/g) was reached in about 4 months. The elimination T1/2 in blood was 26 days. I-Hg constituted 7% of T-Hg in blood. The average concentration of MeHg in occipital pole and thalamus was about 3 micrograms Hg/g at 6 months and 4.5 micrograms Hg/g at 12-18 months. Accumulation in brain seemed to be biphasic. Following termination of 12 months exposure, elimination T1/2 for MeHg in brain was 35 days. I-Hg constituted about 9% of T-Hg in brain at 6-12 months, 18% at 18 months, and 74% at 6 months after termination of exposure. The I-Hg concentrations were somewhat higher in thalamus than in occipital pole. The elimination T1/2 for I-Hg was extremely long, on the order of years. Most likely, the I-Hg was formed by demethylation of MeHg in the brain. In monkeys exposed to HgCl2, blood levels of 0.6 micrograms I-Hg/g gave rise to brain I-Hg levels of about 0.1 micrograms/g only. In three heavy weight monkeys (5.0-6.1 kg body wt) exposed to MeHg, blood Hg increased to about 2 micrograms Hg/g, indicating a limited distribution of MeHg to fat. The Hg concentrations in brain (7-22 micrograms Hg/g) were considerably higher than those in normal weight monkeys, due to the high blood Hg levels in combination with a high brain-to-blood distribution ratio.

Administration, Oral↗
PubMed1994

Regional cerebral blood flow distribution in newly diagnosed schizophrenia and schizophreniform disorder.

Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used to study subjects under resting conditions and during performance of the Wisconsin Card Sorting Test. The study is a replication of a previous investigation in an independent series of patients and healthy volunteers. The patients had significantly lower relative blood flow in prefrontal regions during activation than did the healthy volunteers. An earlier series of 19 patients and 7 healthy volunteers was studied using exactly the same procedure. Analyses of the combined samples from the two studies (43 patients and 24 healthy volunteers) showed the patients to have significantly lower relative flow in prefrontal regions both at rest and during activation and higher flow in the left striatum during activation. The same finding emerged when analyses were confined to drug-naive patients and patients educationally matched to the healthy volunteers. The study suggests a defective frontostriatal interrelationship in schizophrenia and schizophreniform disorder.

Adolescent↗
PubMed1994

Absence of vasoactive peptide release from brain to cerebral circulation during onset of migraine with aura.

In eight patients carotid angiography was required for evaluation of transient neurological attacks. Cerebral blood flow results, angiography and clinical observations subsequently suggested the diagnosis of migraine. We measured plasma concentrations of substance P(SP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in repeated blood samples obtained from the carotid artery and the internal jugular vein in conjunction with cerebral angiography followed by 4 to 6 repeated recordings of regional cerebral blood flow (rCBF) with the intracarotid Xenon-133 injection technique. This technique is known to induce attacks of migraine with aura in many sufferers. Four patients developed aura symptoms. In three this was succeeded by throbbing headache. Typical, migraine-related, focal hypoperfusion occurred in conjunction with the aura symptoms. The remaining four patients had no symptoms or rCBF changes. There were no systematic or statistically significant changes over time in arterial-venous plasma concentrations or in the release rates of any of the peptides. All migraineurs had an overall elevated mean CGRP value compared to control values from the literature. The overall plasma levels of the potent vasoconstrictor NPY were higher (p < 0.10) in the group that developed symptoms and rCBF changes (136 pmol/l) than in the non-symptomatic group (97 pmol/l). The difference in NPY levels could perhaps be associated with the focal rCBF decrease seen in the attack group.

Adult↗
PubMed1994

Cerebral oxygen extraction, oxygen consumption, and regional cerebral blood flow during the aura phase of migraine.

BACKGROUND AND PURPOSE: The aura phase of migraine is associated with focal blood flow changes, but it has been largely unknown whether these changes are correlated to changes in the cerebral metabolism. METHODS: Eight patients required carotid angiography for evaluation of transient neurological attacks. Cerebral blood flow (CBF) results, angiography, and clinical observations subsequently suggested the diagnosis: migraine with aura and occasional aura attacks without headache. In the same setting the cerebral angiography was followed by four to six repeated recordings of regional CBF using the intra-arterial 133Xe injection method. Blood samples were drawn from the carotid artery and the internal jugular vein to measure oxygen extraction fraction and cerebral metabolic rate for oxygen. RESULTS: The intracarotid regional CBF technique provoked aura symptoms and typical, migraine-related, posterior focal hypoperfusion in four patients, followed by typical unilateral headache in three patients. The remaining four patients had no symptoms or regional CBF changes during the examination. There was a significant increase (mean, 13%) of global oxygen extraction fraction in the four patients during aura symptoms, whereas no significant changes of oxygen extraction fraction were found in the nonsymptomatic group. The increase in global oxygen extraction fraction in the symptomatic group coincided with a drop of hemispheric CBF (mean, 12%). Cerebral metabolic oxygen rate remained essentially unchanged, as did PaCO2. CONCLUSIONS: The data presented suggest that the focal flow reduction during the migraine-aura phase is not a secondary phenomenon of reduced cerebral metabolism. However, arteriolar vasoconstriction might offer a possible explanation for the regional CBF changes observed during the migraine aura.

Adult↗
PubMed1994

Speech localization using repetitive transcranial magnetic stimulation.

To evaluate whether repetitive transcranial magnetic stimulation (RTMS) may be used for speech localization, we compared the results from RTMS with the intracarotid amobarbital test (IAT) in 21 patients undergoing surgical treatment (amygdalohippocampectomy or anterior temporal lobe resection) for medically intractable partial epilepsy. None of the patients had aphasia. We stimulated the temporal and frontal cortex on each side at a frequency of 30 Hz for 1 second and increased the intensity until speech was inhibited. A list of words and forward and backward counting were used to test speech function. The IAT was performed on the hemisphere of proposed surgery by unilateral injection and simultaneous regional cerebral blood flow (rCBF) recordings. In one patient, there was doubt about hemisphere dominance and a second bilateral IAT was performed. Fifteen patients had left-sided speech dominance; one, left-sided dominance and a moderate right-sided speech inhibition; two, right-sided speech dominance; and one, bilateral speech representations (bilateral injection at the IAT) with both techniques. One patient showed bilateral with right-sided speech dominance by RTMS and showed right-sided speech inhibition with right-sided injection only at the IAT procedure. One patient differed from the rest, showing bilateral representations with right-sided speech dominance with RTMS and left-sided speech inhibition by IAT with left-sided injection only. The concordance was 95%. None of the patients had seizures provoked by the procedure. We conclude that speech localization with RTMS shows a high concordance with the results from the IAT and may be useful in addition to traditional techniques in speech localization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Retention of 99mTc-bicisate in the human brain after intracarotid injection.

99mTc-bicisate (ECD) was injected as a bolus into the internal carotid artery, and cerebral uptake and retention were recorded with fast-rotating single photon emission computed tomography (SPECT) equipment in four patients suffering from temporal lobe epilepsy. Quantitative regional cerebral blood flow (rCBF) was measured tomographically with the 133Xe inhalation technique. We applied a three-compartment kinetic model and algorithms modified from a previous analysis of 99mTc d,l-hexamethylpropyleneamine oxide (HM-PAO) kinetics. The bicisate brain uptake and retention curve was very similar to that of HM-PAO, and it can be described by a triexponential function including an initial steep component representing the vascular transmitted spike, a second less steep component representing back-diffusion from brain tissue to blood, and a third, very slow component, representing the very slow loss due to incomplete retention of the deesterified hydrophilic metabolites. Computerized curve-fitting on data from three patients gave average kinetic values for the first-passage (unilateral) extraction of E = 0.60 (range, 0.59-0.61); the overall retained fraction of the tracer supplied was R = 0.44 (0.43-0.45), and the conversion/clearance ratio was alpha = k3/k2 = 2.59 (2.38-2.77). This alpha is higher than that for HM-PAO, and therefore bicisate uptake as a function of blood flow is more linear than in HM-PAO. Less correction for backdiffusion is therefore needed. From 1 to 24 h there was an average loss of hydrophilic tracer of 3.5%/h, but the late distribution images were essentially unchanged over time, pointing to practically the same rate of loss in all regions.

Adolescent↗
PubMed1993

Benzodiazepine receptor equilibrium constants for flumazenil and midazolam determined in humans with the single photon emission computer tomography tracer [123I]iomazenil.

This study is based on the steady state method for the calculation of Kd values recently described by Lassen (J. Cereb. Blood Flow Metab. 12 (1992), 709), in which a constant infusion of the examined nonradioactive ligand is used with a bolus injection of tracer. Eight volunteers were examined twice, once without receptor blockade and once with a constant degree of partial blockade of the benzodiazepine receptors by infusion of nonradioactive flumazenil (Lanexat) or midazolam (Dormicum). Single photon emission computer tomography and blood sampling were performed intermittently for 6 h after bolus injection of [123I]iomazenil. The tracer in plasma was determined by high-pressure liquid chromatography and also by a simple octanol extraction procedure. The free concentration of flumazenil and midazolam in plasma water averaged 52% and 3.5% of that in whole plasma. The Kd values for the entire cortical rim for flumazenil were 7.4, 10.0, 10.3 and 17.7 nmol/l plasma water and, for midazolam, 73, 76, 58 and 30 nmol/l plasma water. The variation exceeds random methodological error and is probably due to interindividual differences in receptor affinity. The Kd level of midazolam is considerably higher than expected from the results of in vitro studies.

Adolescent↗
PubMed1993

Brain mapping in thinking and language function.

Regional cerebral blood flow, rCBF, is coupled to regional cerebral metabolism and changes in rCBF reflects changes in neuronal activity. rCBF studies have provided information about the functions of a great number of cortical regions in the normal human brain. Outside the motor areas and sensory association areas there are areas committed to the transformation of information retrieved or generated within the brain itself. Language is processed within these regions. In contrast to the general clinical impression the functional mapping methods reveal that there is a large number of cortical regions activated bilaterally during language processing. Pure intrinsic brain work causes a profound activation of the cerebral cortex. Different types of thinking are seen to activate different sectors of the cortical space.

Brain↗