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O B Paulson

Publications and source records attributed to O B Paulson.

At least 19 recordsLinked to original sources
PubMed2006

Structural brain abnormalities in early onset first-episode psychosis.

BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder, delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed that schizophrenia patients (n = 15) had significantly larger lateral ventricles as compared to controls. Duration and dose of antipsychotics correlated negatively with global gray matter volume in minimally medicated patients (n = 18). CONCLUSION: Findings of white matter changes and enlarged lateral ventricles already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis.

Adolescent↗
PubMed2006

A prospective PET study of patients with glioblastoma multiforme.

OBJECTIVE: To study the post-surgical metabolic and structural cerebral changes in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: We examined ten patients prospectively with newly diagnosed GBM. All patients were primarily treated with surgery, followed by chemotherapy (carmustine, cisplatine and etoposide) and radiotherapy. Positron emission tomography (PET) was used to measure tumor- and cerebral metabolism. CT or MRI was used to estimate tumor volume by measurements of tumor area. RESULTS: Tumor metabolism was not increased during chemotherapy (P = 0.71), but increased during radiotherapy (P = 0.01). CT/MRI showed similar results with no increase in tumor area during chemotherapy (P = 0.33) but increase during radiotherapy (P = 0.002). During the entire study, tumor metabolism and area increased evenly (P = 0.01). CONCLUSIONS: Our study did not show a gain of PET compared with structural imaging in the prospective evaluation of GBM. We found a difference in metabolic increase and tumor growth between the two treatment regimens, although this finding has limited relevance due to the design of the study.

Adult↗
PubMed2005

Decline in intelligence is associated with progression in white matter hyperintensity volume.

OBJECTIVES: To quantify the time course of white matter hyperintensities (WMH) and assess the association between progression and cognitive decline in non-demented octogenarians. METHODS: From a Danish cohort of 698 people born in 1914, 26 participated in neuropsychological assessment (Wechsler adult intelligence scale) initiated at age 50, including cognitive testing and cerebral magnetic resonance imaging at the 80 and 85 year studies. WMH volumes were quantified and partial correlations were calculated between WMH volume change and decline in WAIS scores from 80 to 85. RESULTS: Progression in WMH volume ranged from 0 ml to 20.7 ml, providing a median increase of 2.6 ml (range 0.1 to 20.7, p<0.001) and, with a mean time interval between scans of 3.8 years, a rate of progression of 0.63 (0 to 6.8) ml/year. WMH volume measures for the two hemispheres were highly correlated (r = 0.95) and did not differ significantly. Increase in WMH volume was correlated with a simultaneous decline in verbal IQ (r = -0.65, p = 0.001), while baseline WMH was associated with subsequent decline in performance subtests (digit symbol, r = -0.57, p = 0.02). CONCLUSIONS: The association between WMH and decline in essential cognitive abilities even in well preserved elderly people suggests that WMH should be regarded as a risk factor for cognitive impairment and dementia.

Aged↗
PubMed2004

Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation.

Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked to the SPG4 locus on chromosome 2p as previously reported for pure HSP. Sequence analysis of the SPG4 (spastin) gene identified a novel 1593 C > T (GLN490Stop) mutation leading to premature termination of exon 12 with ensuing truncation of the encoded protein. However, the mutation was only identified in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance of these features to SPG4 is unclear. Electrophysiologic investigation showed increased central conduction time at somatosensory evoked potentials measured from the lower limbs as the only abnormal finding in two affected individuals with the SPG4 mutation. Moreover, PET of one patient showed significantly relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations.

Adenosine Triphosphatases↗
PubMed2002

The role of action knowledge in the comprehension of artefacts--a PET study.

Activation of the left ventral premotor cortex (PMv) has in previous imaging studies been associated with the processing of visually presented artefacts. It has been suggested that this activation reflects processing of action knowledge and that action knowledge contributes to the comprehension of artefacts. The purpose of the present study was to test whether activation of the left PMv is common for all tasks involving the comprehension of artefacts or whether it is task specific. This was done by comparing performance and regional cerebral blood flow (rCBF) associated with two categorization tasks and two naming tasks divided by category (natural objects vs artefacts). The left PMv (BA 6/44) was more activated by the categorization task for artefacts than by the categorization task for natural objects and the naming task for artefacts. However, the left PMv was not associated with the contrast between the naming task for artefacts and the naming task for natural objects nor with the processing of artefacts in general. If the PMv does mediate action knowledge, these results suggest that action knowledge does not contribute directly to the comprehension of artefacts but may support the categorization of artefacts. The significance of these findings is discussed in relation to category-specific recognition impairments for artefacts.

Adult↗
PubMed2002

Brain activity related to integrative processes in visual object recognition: bottom-up integration and the modulatory influence of stored knowledge.

We report evidence from a PET activation study that the inferior occipital gyri (likely to include area V2) and the posterior parts of the fusiform and inferior temporal gyri are involved in the integration of visual elements into perceptual wholes (single objects). Of these areas, the fusiform and inferior temporal gyri were more activated by tasks with recognizable stimuli than by tasks with unrecognizable stimuli. We propose that the posterior parts of the fusiform and inferior temporal gyri, compared with the inferior occipital gyri, are involved in higher level integration, due to the involvement of re-entrant activation from stored structural knowledge. Evidence in favor of this interpretation comes from the additional finding that activation of the anterior part of the left fusiform gyrus and a more anterior part of the right inferior temporal gyrus, areas previously associated with access to stored structural knowledge, was found with recognizable stimuli, but not with unrecognizable stimuli. This latter finding also indicates: (i) that subjects may not refrain from (automatically) identifying objects even if they only have to attend to the objects' global shape, and (ii) that perceptual and memorial processes can be dissociated on both functional and anatomical grounds. No evidence was obtained for the involvement of the parietal lobes in the integration of single objects.

Adult↗
PubMed2002

Blood-brain barrier, brain metabolism and cerebral blood flow.

For optimal function of the brain with its meticulous operations, an adequate and constant micro environment seems to be a prerequisite. This is secured by the blood-brain barrier which is impermeable to hydrophilic substances, with notable exceptions such as glucose, which cross the barrier by a mechanism of facilitated diffusion. A constant micro environment is further secured by the blood flow which is balanced to the metabolic demand of the cerebral tissue and which also contributes to the maintenance of a constant pH. During activation, blood flow and glucose consumption increase more than oxygen consumption in activated areas of the brain. The flow increase forms the physiological basis for measurement and mapping of functional activation using positron emission tomography and the changes in the metabolic pattern which has been called uncoupling of flow and oxygen metabolism is the basis for such measurements using functional magnetic resonance imaging.

Animals↗
PubMed2001

[Reduced metabolism in cerebral cortex correlates with MRI changes and cognitive dysfunction in patients with disseminated sclerosis].

INTRODUCTION: Magnetic resonance imaging (MRI) lesion load is widely used in the clinical evaluation of patients with multiple sclerosis (MS), but little is known about the associated changes in cortical activation. For this purpose, we studied the association between the corticocerebral metabolic rate of glucose (CMRglc) and the MRI T2-weighted total lesion area (TLA). In addition, we investigated the correlation between cognitive and neurological disability and CMRglc. METHODS: Twenty-three patients with clinically definite MS underwent measurements of the CMRglc, TLA, motor-evoked potentials (MEP), and cognitive and neurological disability. CMRglc was calculated with positron emission tomography (PET) and 18-F-deoxyglucose (FDG) and compared to that of nine healthy controls. RESULTS: A reduction in CMRglc (p < 0.01) was found in cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (rho = -0.66; p = 0.001), and rCMRglc correlated with the regional lesion load in all cerebral lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability were also correlated (rho = 0.58; p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance, as well as the TLA. There was no correlation between CMRglc and neurological disability (expanded disability status scale [EDSS]) or MEP. CONCLUSION: Global and regional cortical CMRglc is significantly reduced in patients with MS compared to healthy controls. The reductions in CMRglc furthermore correlate with the TLA, as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on corticocerebral neural function.

Adult↗
PubMed2001

Idiopathic normal-pressure hydrocephalus: evaluation and findings in a multidisciplinary memory clinic.

The diagnostic evaluation of patients with possible idiopathic normal-pressure hydrocephalus (INPH) is traditionally performed in the settings of either neurological, neurosurgical or psychiatric departments. The diagnostic procedure and findings in 71 consecutive patients referred with a clinical and radiological suspicion of INPH to our out-patient multidisciplinary memory clinic are evaluated. Primary diagnoses and potential concomitant disorders considered of secondary importance for the symptomatologies were established. Abnormal hydrodynamics, demonstrated by intraventricular pressure monitoring and infusion test were mandatory for the diagnosis of INPH. Mean age was 68 years and mean Mini-Mental State Examination (MMSE) score was 22. DSM IV criteria of dementia were fulfilled in 42%. In half of the referred patients (n=36), the suspicion of INPH was already disproved subsequently to the evaluation programme performed in the outpatient clinic. The main primary diagnosis was cerebrovascular disease (CVD) comprising 27% (n=19) of the referrals, whereas INPH was diagnosed in only 20% (n=14). Shunt improvement rate was 72%. The remaining patients were diagnosed as having one of 26 different conditions. A multiplicity of disorders mimics the INPH syndrome, with CVD being the primary differential diagnosis. Evaluating patients with possible INPH in an outpatient multidisciplinary memory clinic is an effective and rational diagnostic approach.

Adult↗
PubMed2001

The (18)F-fluorodeoxyglucose lumped constant determined in human brain from extraction fractions of (18)F-fluorodeoxyglucose and glucose.

Quantification of regional cerebral glucose metabolism (CMRglc) using positron emission tomography and 18F-fluorodeoxyglucose (PET-FDG) requires knowledge of the correction factor between FDG and glucose net clearance, the FDG lumped constant (LC). Because diverging values for LC have been obtained, the authors reevaluated LC by measuring the ratio of the cerebral net extraction fractions of FDG (E*) and glucose (E) from arteriovenous cerebral measurements. Thirty subjects were studied (mean age = 25 +/- 4 years): 12 during a programed infusion of FDG and 18 after a bolus injection of FDG. In the infusion study, LC was calculated as the ratio E*/E. In the bolus study, E* was calculated from the slope of a Patlak-Gjedde plot. Lumped constant was significantly smaller in the infusion study as compared with the bolus study (0.48 +/- 0.16 vs. 0.81 +/- 0.27, P < 0.001). In 4 subjects studied during continuous FDG infusion for 2.5 hours, LC decreased to 0.36 +/- 0.11. These results suggest that the "steady-state" method underestimates LC because E* continues to decline because of significant labeled product. Further, the authors provide evidence for resetting of LC toward a greater value. The subsequent resetting of CMRglc provides a physiologically more meaningful estimate and allows for comparison of CMRglc values between different methodologies.

Brain↗
PubMed2001

Using (10)CO2 for single subject characterization of the stimulus frequency dependence in visual cortex: a novel positron emission tomography tracer for human brain mapping.

Carbon-10-labeled carbon dioxide ((10)CO2) with a half-life of 19.3 seconds offers almost ideal characteristics as a positron emission tomography (PET) tracer for assessment of the regional cerebral blood flow (rCBF) distribution, enabling multiple independent measurements at short intervals. To appraise the feasibility of (10)CO2 for localizing and characterizing human brain function in single subjects, the authors chose a well-characterized activation paradigm. In 6 healthy volunteers, 50 to 64 independent PET scans of the rCBF distribution were acquired while viewing an annular reversing checkerboard presented at 10 reversal frequencies between 0.03 and 30 Hz. Changes in regional cerebral activity as a function of reversal frequency were modeled in every subject using a set of polynomial basis functions, which, as predicted, showed highly significant second or third order relations located in the striatal cortex. Correlation coefficients (R2) ranged from 0.46 to 0.63. The average intersubject maximal response relative to the 0.03 Hz condition was 8.0% +/- 1.7% SD occurring at stimulus contrast reversal frequencies between 6 and 15 Hz with an average of 11.8 +/- 3.8 (SD) Hz. From the qualitative and quantitative replication of previous results it is concluded that (10)CO2 PET is a feasible technique for human brain mapping studies and a great improvement compared with the existing oxygen-15-labeled water (H(2)(15)O) PET method, particularly for single subject studies and parametric design.

Brain Mapping↗
PubMed2001

Benzodiazepine receptor quantification in Huntington's disease with [(123)I]omazenil and SPECT.

OBJECTIVES: Increasing evidence suggests that metabolic changes predate neuronal death in Huntington's disease and emission tomography methods (PET and SPECT) have shown changes in glucose consumption and receptor function in early and possibly even presymptomatic disease. Because the GABA(A)-benzodiazepine receptor complex (BZR) is expressed on virtually all cerebral neurons BZR density images may be used to detect neuronal death. In this study the regional cerebral [(123)I]iomazenil binding to BZR was determined in patients with Huntington's disease and normal controls by a steady state method and SPECT. METHODS: Seven patients mildly to moderately affected by Huntington's disease and seven age matched controls were studied. Brain CT was performed on all subjects. In each subject two [(123)I]iomazenil-SPECT measurements were acquired-one with and one without infusion of flumazenil. The affinity constant of flumazenil (Kd) was calculated from the paired distribution volumes (DV) and the free plasma flumazenil concentration. The distribution volume of [(123)I]iomazenil in the unblocked condition (DV(0)) reflects the ratio between BZR density and Kd. RESULTS: Flumazenil Kd was similar in the Huntington's disease group and the control group (11.3 v 11.2 mM). For the Huntington's disease group a 31% reduction in striatal DV(0) (p=0.03) was found. In the cortical regions, DV(0) was similar in patients and in controls. In Huntington's disease, DV(0) correlated significantly with functional capacity (p=0.04) and chorea symptoms (p=0.02). The clinically least affected patients displayed DV(0)s within the range of those of the control group (19-35 ml/ml). CONCLUSIONS: The finding of an unchanged Kd of flumazenil in patients indicates that the BZR is functionally intact in Huntington's disease. That is, the reduction in DV(0) for BZR represents a selective decrease in the number of striatal BZRs. DV(0) significantly correlated with functional loss and [(123)I]iomazenil-SPECT could be an important tool for validation of the effect of future therapeutic strategies aimed at limiting oxidative stress and free radicals in Huntington's disease.

Adult↗
PubMed2001

Single photon emission computed tomography and apolipoprotein E in Alzheimer's disease: impact of the epsilon4 allele on regional cerebral blood flow.

The aim of this study was to examine the impact of the apolipoprotein E (APOE) epsilon4 allele on semiquantitative regional cerebral blood flow (rCBF) in Alzheimer's disease. Single photon emission computed tomography technetium (SPECT) with (99m)Tc d,l-hexamethyl propylenamine oxine was used to determine rCBF in 41 consecutive patients (18 males/23 females) with probable Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria (mean age 71.0 years; range 54-85). The mean Mini-Mental State Examination (MMSE) score was 20.4 (range 10-30). After normalization of CBF to mean blood flow in the cerebellum, values for rCBF in several cortical regions of interest, side-to-side asymmetry indices, and anterior-posterior ratios were calculated. Determination of the APOE genotype from blood samples was performed using restriction enzyme polymerase chain reaction technique. Multivariate regression analyses and the Wilcoxon rank-sum test for unpaired data (Mann-Whitney) were used for statistical analysis. The patients comprised 27APOE epsilon4-positive and 14APOE epsilon4-negative individuals. Five patients were APOE epsilon4 homozygotes. APOE epsilon4-positive patients had significantly reduced rCBF in the right frontal and left occipital lobes. On nonparametric analysis, the most prominent differences between epsilon4-negative and epsilon4-positive patients were demonstrated in subregions representing the frontal association cortex (Mann-Whitney, P < .01). Age-stratified analysis suggested that these findings could be demonstrated predominantly in the elderly patients. The results of this study suggest that the APOE genotype in itself may have an impact on the pattern of rCBF deficits in Alzheimer's disease. The more pronounced reduction of rCBF in frontal association cortex observed in elderly APOE epsilon4-positive patients might predict clinical progression.

Age Factors↗
PubMed2001

Blood-brain barrier transport and brain metabolism of glucose during acute hyperglycemia in humans.

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and [(18)F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 +/- 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 +/- 0.008 vs. 0.059 +/- 0.031 mL/100 g.min). The unidirectional clearance of [(18)F]fluorodeoxyglucose (K(1)*) was reduced from 0.108 +/- 0.011 to 0.061 +/- 0.005 mL/100 g.min (P < 0.0004). During hyperglycemia, global CMR(glc) remained constant (21.4 +/- 1.2 vs. 23.1 +/- 2.2 micromol/100 g.min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMR(glc), no regional difference in CMR(glc) was found. Likewise, CBF remained unchanged. The reduction in K(1)* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMR(glc).

Adult↗
PubMed2001

No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation.

Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral circulation is uncertain. Hence, the present study investigated the effect on CBF autoregulation of blocking of angiotensin AT2-receptors with PD 123319 in spontaneously hypertensive rats (SHR). Anaesthetised and ventilated SHR were given PD 123319, 0.36 mg/kg/min, intravenously, and compared with a control group. CBF was measured by the intracarotid 133xenon injection method and BP was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis. PD 123319 did not influence baseline CBF, but resulted in a minor BP decrease (10 control and 10 treated rats). The lower limit of CBF autoregulation (eight treated and eight control) as well as the upper limit of CBF autoregulation (eight treated and eight control) were not significantly different in PD 123319 and control animals (lower limit treated 102+/-4 mmHg and control 94+/-4; NS, and upper limit treated 171 +/- 10 mmHg and control 162+/-7; NS). These findings indicate that acute AT2-receptor blockade does not influence CBF autoregularion.

Angiotensin Receptor Antagonists↗
PubMed2000

SPECT tracer [(123)I]IBZM has similar affinity to dopamine D2 and D3 receptors.

Emission tomography investigations of the pathophysiological involvement of the cerebral dopaminergic transmitter system in the living human brain relies heavily on a careful selection of the most suitable radioligand. In recent years, many clinical studies have employed [(123)I]IBZM in SPECT studies. The aim of the present study was to characterize the binding of IBZM to dopaminergic receptor subtypes as a means of elucidating which receptor subtypes are visualized and examined by [(123)I]IBZM. The affinity of IBZM for each of the major human dopamine receptors (D1, D2(short), D3, D4(4. 2), and D5 receptor) was determined by competitive radioligand binding assay using membranes prepared from clonal cell lines expressing the different subtypes. Radioligands with high affinity for the D1(A) and D5 receptors ([(3)H]SCH-23390), dopamine D2(short) and D4(4.2) receptors ([(3)H]Spiroperidol), and dopamine D3 receptor ([(3)H]7-OH-DPAT) were used to measure specific binding. Corresponding unlabeled displacing ligands for determination of nonspecific binding were employed. Assays were performed at 25 degrees C. These experiments show that for IBZM K(i) values were 1.6 nM for dopamine D2(s) receptors and 2.2 nM for dopamine D3 receptors. There was no binding of IBZM to D1(A), D5, or D4(4.2) receptors. In conclusion, when [(123)I]IBZM is used as SPECT tracer, the studies reflect dopaminergic D2 as well as D3 receptor binding.

Animals↗
PubMed2000

Dopamine D(2) receptor quantification in extrastriatal brain regions using [(123)I]epidepride with bolus/infusion.

The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D(2) receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [(123)I]epidepride for the quantification of striatal and extrastriatal dopamine D(2) receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample. Based on bolus experiments, an algorithm using conventional convolution arguments for prediction of the outcome of a bolus/infusion (B/I) experiment was applied. It was predicted that a B/I protocol with infusion of one-third of the initial bolus per hour would be appropriate. Steady-state conditions were attained in extrastriatal regions within 3-4 h but the infusion continued up to 7 h in order to minimize the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride has a unique signal-to-noise ratio compared to [(123)I]IBZM but present difficulties for steady-state measurements of striatal regions. The bolus/infusion approach is particularly feasible for quantification of the binding potential in extrastriatal regions.

Adult↗