PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Heterogeneity Mapping”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed2000

Phylogenetic analysis and trait evolution in Australian lineages of drywood termites (Isoptera, Kalotermitidae).

A phylogenetic analysis of Australian drywood termites (Isoptera, Kalotermitidae) based on partial sequence from the cytochrome oxidase II (COII) and cytochrome b genes is presented. In addition to providing new information on the evolutionary relationships among 25 species from seven genera, we evaluate the relative likelihoods of alternative topological hypotheses, including those derived from morphology-based classifications. We also test the applicability of a molecular clock for estimating the age of the Kalotermitidae and infer the evolution of species-specific variation for habitat type and soldier caste phragmosis by mapping this information onto the independently derived phylogeny. Maximum-likelihood analysis of both nucleotide and protein sequences from a multigene data set jointly support a single topology, which is shown to be the best estimate of the true phylogeny among the alternatives tested. Our results support the monophyly of all genera but question the discrimination between Procryptotermes and Cryptotermes. A basal dichotomy among generic groups suggests two principle lines of divergence within the family. Intergeneric relationships show mixed congruence to previous proposals, resulting in one morphology-based classification being rejected. A molecular clock hypothesis is not supported due to significant among-lineage rate heterogeneity in the COII gene. Patterns revealed through trait mapping suggest that the most recently diverged taxa tend to occupy the driest habitats and that these same taxa reflect a defensive transition away from large mandibulate soldiers toward small phragmotic soldiers. The association between habitat and defensibility supports the hypothesis that these two characters have been tightly linked throughout the social diversification of termites.

Animals↗
PubMed2004

Genome scan for QTLs underlying bone size variation at 10 refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement.

To identify quantitative trait loci (QTLs) underlying variation in bone size, we conducted a whole-genome linkage scan in 53 pedigrees with 630 subjects using 380 microsatellite markers. Lumbar area 1, 2, 3, and 4 at the spine, femoral neck, trochanter, intertrochanter areas at the hip, ultradistal, mid-distal, and one-third distal areas at the wrist were measured by dual-energy X-ray absorptiometry (DXA), and adjusted for age, height, weight, and sex. Two-point and multipoint linkage analyses were performed for skeletal bone size at each site and their composite measurements using the SOLAR package. Two chromosomal regions (1q22 and 10q21) were identified with significant evidence of linkage (LOD > 4.32) to one-third distal area, and three were identified with suggestive evidence of linkage (LOD > 2.93) to bone size in one skeletal site. Our results indicated that the low power of QTLs mapping for composite phenotypic measurements may result from genetic heterogeneity of complex traits.

Bone and Bones↗
PubMed2006

A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7.

Hereditary hemorrhagic telangiectasia (HHT) is a genetically and clinically heterogeneous multisystem vascular dysplasia. Mutations of the endoglin and ACVRL1 genes are known to cause HHT. However, existence of HHT families in which linkage to these genes has been excluded has suggested that other gene(s) can cause HHT in some families. Recently, a family was reported to be linked to chromosome 5q, the HHT3 locus. Here we report on linkage results on a family with classic features of HHT, albeit a less severe phenotype with regards to epistaxis and telangiectases, in which linkage to HHT1, HHT2, and HHT3 is ruled out. Whole genome linkage analysis and fine mapping results suggested a 7 Mb region on the short arm of chromosome 7 (7p14) between STR markers D7S2252 and D7S510. We obtained a maximum two point LOD score of 3.60 with the STR marker D7S817. This region was further confirmed by haplotype analysis. These findings suggest the presence of another gene causing HHT (HHT4). The features in this family that strongly suggest the presence of a hereditary, multisystem vascular dysplasia would be easily missed during the typical evaluation and management of a patient with an AVM. This family helps emphasize the need to obtain a very detailed, targeted medical and family history for even mild, infrequent but recurring nosebleed, subtle telangiectases. Further studies of the candidate region and the identification of the gene responsible for the vascular anomalies in this family will add to our understanding of vascular morphogenesis and related disorders.

Activin Receptors, Type II↗
PubMed2005

A new syndrome, congenital extraocular muscle fibrosis with ulnar hand anomalies, maps to chromosome 21qter.

BACKGROUND: Congenital fibrosis of the extraocular muscles (CFEOM) is a heterogeneous group of disorders that may be associated with other anomalies. The association of a CFEOM syndrome with ulnar hand abnormalities (CFEOM/U) has not been reported to date. OBJECTIVE: To describe a new autosomal recessive syndrome of CFEOM and ulnar hand abnormalities, and localise the disease causing gene. METHODS: Clinical evaluation of the affected members and positional mapping. RESULTS: Six affected patients with CFEOM/U (aged 2 to 29 years) from a large consanguineous Turkish family were studied. Ophthalmological involvement was characterised by non-progressive restrictive ophthalmoplegia with blepharoptosis of the right eye. The postaxial oligodactyly/oligosyndactyly of the hands was more severe on the right side. A genome-wide scan established linkage of this new autosomal recessive syndrome to a locus on chromosome 21qter. The multipoint LOD score was 4.53 at microsatellite marker D21S1259, and fine mapping defined a approximately 1.5 Mb critical region between microsatellite marker D21S1897 and the telomere of the long arm. CONCLUSIONS: CFEOM/U maps to a 1.5 Mb region at chromosome 21qter. Future identification of the disease causing gene may provide insights into the development of the extraocular muscles and brain stem alpha motor neurones, as well as anteroposterior limb development.

Adult↗
PubMed2001

Differences in complexity of isolated brachydactyly type C cannot be attributed to locus heterogeneity alone.

Hereditary isolated brachydactyly type C (OMIM 113100) mostly follows an autosomal dominant pattern of inheritance with a marked variability in expression. This phenotype has been mapped to two different loci on chromosomes 12q24 and 20q11.2. The latter locus contains the cartilage-derived morphogenetic protein (CDMP)1 gene, in which a null mutation has been found in patients with malformations restricted to the upper limbs. A more complex brachydactyly type C phenotype has been mapped to chromosome 12q24. Differences in complexity of these phenotypes have been attributed to locus heterogeneity. Clinical subclassification based on the degree of complexity of the phenotype has therefore been suggested. We present patients with a complex brachydactyly type C phenotype in whom there is considerable intra- and interfamilial variability in expression. We show that clinical subclassification based on the complexity of the brachydactyly type C phenotype related to the genetic defect is not feasible. We present evidence that differences in complexity are not only due to locus heterogeneity, but that genetic modifiers and/or environmental factors must also play a role.

Adolescent↗
PubMed1997

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging.

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127+/-31 ml.min-1.100 g-1; group B, 124+/-30 ml.min-1.100 g-1 normal subjects, 105+/-21 ml.min-1.100 g-1 (groups A and B vs normals, P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20+/-0.23; group B, 1.24+/-0.22; normal subjects, 1.23+/-0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71+/-0.67; group B, 2.77+/-1.29; normal subjects, 2. 91+/-1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1+/-4.5 vs 17.0+/-3.0, P<0.05). In group B (coefficient of variation 19.4+/-3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.

Adult↗
PubMed1998

A new autosomal recessive retinitis pigmentosa locus maps on chromosome 2q31-q33.

Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disease. To date, mutations in four members of the phototransduction cascade have been implicated in ARRP. Additionally, linkage of the disease to three loci on 1p, 1q, and 6p has been described. However, the majority of cases are still uncharacterised. We have performed linkage analysis in a large nuclear ARRP family with five affected sibs. After exclusion of several regions of the genome known to contain loci for retinal dystrophies, a genomic search for linkage to ARRP was undertaken. Positive lod scores were obtained with markers on 2q31-q33 (Zmax at theta = 0.00 of 4.03, 4.12, and 4.12 at D2S364, D2S118, and D2S389, respectively) defining an interval of about 7 cM for this new ARRP locus, between D2S148 and D2S161. Forty-four out of 47 additional ARRP families, tested with markers on 2q32, failed to show linkage, providing evidence of further genetic heterogeneity.

Adult↗
PubMed2003

Spontaneous initiation and termination of complex rhythms in cardiac cell culture.

INTRODUCTION: Complex cardiac arrhythmias often start and stop spontaneously. These poorly understood behaviors frequently are associated with pathologic modification of the structural heterogeneity and functional connectivity of the myocardium. To evaluate underlying mechanisms, we modify heterogeneity by varying the confluence of embryonic chick monolayer cultures that display complex bursting behaviors. A simple mathematical model was developed that reproduces the experimental behaviors and reveals possible generic mechanisms for bursting dynamics in heterogeneous excitable systems. METHODS AND RESULTS: Wave propagation was mapped in embryonic chick myocytes monolayers using calcium-sensitive dyes. Monolayer confluence was varied by plating cultures with different cell densities and by varying times in culture. At high plating densities, waves propagate without breaks, whereas monolayers plated at low densities display spirals with frequent breaks and irregular activation fronts. Monolayers at intermediate densities display bursting rhythms in which there is paroxysmal starting and stopping of spiral waves of activity. Similar spatiotemporal patterns of activity were also observed as a function of the time in culture; irregular activity dominates the first 30 hours, followed by repetitive bursting dynamics until 54 hours, after which periodic target patterns or stable spirals prevail. In some quiescent cultures derived from older embryos, it was possible to trigger pacemaker activity following a single activation. We are able to reproduce all of these behaviors by introducing spatial heterogeneity and varying neighborhood size, equivalent to cell connectivity, in a spontaneous cellular automaton model containing a rate-dependent fatigue term. CONCLUSION: We observe transitions from irregular propagating waves, to spiral waves that spontaneously start and stop, to target waves originating from localized pacemakers in cell culture and a simple theoretical model of heterogeneous excitable media. The results show how physiologic properties of spontaneous activity, heterogeneity, and fatigue can give rise to a wide range of different complex dynamic behaviors similar to clinically observed cardiac arrhythmias.

Algorithms↗
PubMed1992

Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to influence the structure of hnRNA and participate in the processing of hnRNA to mRNA. The hnRNP U protein is an abundant nucleoplasmic phosphoprotein that is the largest of the major hnRNP proteins (120 kDa by SDS-PAGE). HnRNP U binds pre-mRNA in vivo and binds both RNA and ssDNA in vitro. Here we describe the cloning and sequencing of a cDNA encoding the hnRNP U protein, the determination of its amino acid sequence and the delineation of a region in this protein that confers RNA binding. The predicted amino acid sequence of hnRNP U contains 806 amino acids (88,939 Daltons), and shows no extensive homology to any known proteins. The N-terminus is rich in acidic residues and the C-terminus is glycine-rich. In addition, a glutamine-rich stretch, a putative NTP binding site and a putative nuclear localization signal are present. It could not be defined from the sequence what segment of the protein confers its RNA binding activity. We identified an RNA binding activity within the C-terminal glycine-rich 112 amino acids. This region, designated U protein glycine-rich RNA binding region (U-gly), can by itself bind RNA. Furthermore, fusion of U-gly to a heterologous bacterial protein (maltose binding protein) converts this fusion protein into an RNA binding protein. A 26 amino acid peptide within U-gly is necessary for the RNA binding activity of the U protein. Interestingly, this peptide contains a cluster of RGG repeats with characteristic spacing and this motif is found also in several other RNA binding proteins. We have termed this region the RGG box and propose that it is an RNA binding motif and a predictor of RNA binding activity.

Amino Acid Sequence↗
PubMed2006

Pacing-induced heterogeneities in intracellular Ca2+ signaling, cardiac alternans, and ventricular arrhythmias in intact rat heart.

Optical mapping studies have suggested that intracellular Ca2+ and T-wave alternans are linked through underlying alternations in Ca2+ cycling-inducing oscillations in action potential duration through Ca2+-sensitive conductances. However, these studies cannot measure single-cell behavior; therefore, the Ca2+ cycling heterogeneities within microscopic ventricular regions are unknown. The goal of this study was to measure cellular activity in intact myocardium during rapid pacing and arrhythmias. We used single-photon laser-scanning confocal microscopy to measure Ca2+ signaling in individual myocytes of intact rat myocardium during rapid pacing and during pacing-induced ventricular arrhythmias. At low rates, all myocytes demonstrate Ca2+ alternans that is synchronized but whose magnitude varies depending on recovery kinetics of Ca2+ cycling for each individual myocyte. As rate increases, some cells reverse alternans phase, giving a dyssynchronous activation pattern, even in adjoining myocytes. Increased pacing rate also induces subcellular alternans where Ca2+ alternates out of phase with different regions within the same cell. These forms of heterogeneous Ca2+ signaling also occurred during pacing-induced ventricular tachycardia. Our results demonstrate highly nonuniform Ca2+ signaling among and within individual myocytes in intact heart during rapid pacing and arrhythmias. Thus, certain pathophysiological conditions that alter Ca2+ cycling kinetics, such as heart failure, might promote ventricular arrhythmias by exaggerating these cellular heterogeneities in Ca2+ signaling.

Animals↗
PubMed1992

Autoradiographic distribution of receptors to FLFQPQRFamide, a morphine-modulating peptide, in rat central nervous system.

The neuropeptide FLFQPQRFamide is a structure related to FMRFamide which is able to inhibit the effects of both endogenous and exogenous opiates. This morphine-modulating activity is mediated via the stimulation of specific FLFQPQRFamide receptors, different from opiate receptors. In vitro quantitative receptor autoradiography was performed on frozen sections of rat central nervous system to characterize binding properties and visualize FLFQPQRFamide receptors using the specific ligand [125I]YLFQPQRFamide, a radio-iodinated analogue of FLFQPQRFamide. [125I]YLFQPQRFamide appeared to interact reversibly with a single class of binding sites (KD = 0.2 nM). The specific binding represented 80% of the total binding at 0.05 nM, the FLFQPQRFamide concentration used in this mapping study. Sites labelled with [125I]YLFQPQRFamide were distributed heterogeneously within the brain and spinal cord. A high density of FLFQPQRFamide binding sites was detected in the most external layers of the dorsal horn of spinal cord and various nuclei of pons and medulla including trigeminal, dorsal tegmental and reticular nuclei. Nucleus of solitary tract, parabrachial, ambiguous and facial nuclei are also intensively labelled. Some structures of mesencephalon and diencephalon exhibited a high density of FLFQPQRFamide binding sites: central gray, raphe nuclei and thalamic nuclei such as parafascicular, laterodorsal, central median, paratenial and paraventricular nuclei. Suprachiasmatic and mammillary nuclei, lateral, posterior and anterior areas of hypothalamus and medial preoptic area exhibited high labelling. FLFQPQRFamide binding sites were also seen in some structures of the dopaminergic meso-cortico-limbic system including ventral tegmental area, cingulate cortex, lateral septum and the head of the caudate-putamen. Dense labelling appeared in the presubiculum of hippocampus. The dissimilar mapping of FLFQPQRFamide and opiate brain receptors confirms our previous pharmacological findings in FLFQPQRFamide binding studies on rat spinal cord membranes, showing that FLFQPQRFamide receptors are different from opiate receptors. There was a good correspondence between localization of binding sites and that of the putative endogenous peptide. Both occur in brain areas previously associated with analgesic action of opiates. However, the mapping of FLFQPQRFamide receptors in the central nervous system suggests that the FLFQPQRFamide system could be implicated in other physiological functions.

Animals↗
PubMed1997

Mapping of ventricular repolarization potentials in patients with arrhythmogenic right ventricular dysplasia: principal component analysis of the ST-T waves.

BACKGROUND: Nonuniform recovery of ventricular excitability has been demonstrated to facilitate the reentry circuits leading to the development of ventricular tachyarrhythmias. This can also occur in arrhythmogenic right ventricular dysplasia (ARVD). In fact, in patients with ARVD, abnormalities of ventricular repolarization are often observed on 12-lead ECGs, but their predictive value for the occurrence of malignant arrhythmias is yet to be established. Because body-surface potential mapping has been proved to be useful for the detection of heterogeneities in ventricular recovery even though they are not revealed by conventional 12-lead ECGs, we attempted to analyze repolarization potentials on the entire chest surface to find abnormalities that can be predictive of ventricular arrhythmias. METHODS AND RESULTS: Body-surface potential maps were recorded from 62 anterior and posterior thoracic leads in 22 patients affected by ARVD, 9 with episodes of sustained ventricular tachycardias (VT) and 13 without. Thirty-five healthy subjects were also studied as control subjects. The 62 chest ECGs were simultaneously recorded, digitally converted at a rate of 2000 Hz, and stored on a hard disk of a body-surface mapping computer system. In each subject, the QRST integral map was obtained by calculating at each lead point the algebraic sum of all instantaneous potentials, from the QRS onset to the T-wave end, multiplied by the sampling interval. In most ARVD patients, we observed a larger-than-normal area of negative values on the right anterior thorax. This abnormal pattern could be explained by a delayed repolarization of the right ventricle. Nevertheless, it was not related to the occurrence of VT in our patient population. To detect minor heterogeneities of ventricular repolarization, the principal component analysis was applied to the 62 ST-T waves recorded in each subject. We assumed that a low value of the first or of the first three components (components 1, 2, and 3) indicates a greater-than-normal variety of the ST-T waves, a likely expression of a more complex recovery process. The mean values of the first three components were not significantly different in ARVD patients and control subjects. Nevertheless, considering the two subsets of patients with and without VT, the values of component 1, components 1 + 2, and component 1 + 2 + 3 were significantly lower in the group of ARVD patients with VT. Values of component 1 < 69% (equal to 1 SD below the mean value for control subjects) were found in 6 of 9 VT patients and in 1 patient without VT (sensitivity, 67%; specificity, 92%). A low value of component 1 was the only variable significantly associated with the occurrence of VT. CONCLUSIONS: Principal component analysis provides a better quantitative assessment of the complexity of repolarization than other ECG measurements. When applied to ARVD patients, principal component analysis of the ST-T waves recorded from the entire chest surface revealed abnormalities not detected by conventional ECG that can be considered indexes of arrhythmia vulnerability.

Adolescent↗
PubMed2002

The effect of volume currents due to myocardial anisotropy on body surface potentials.

Changes in anterior and posterior body surface potential maps (BSPMs) due to myocardial anisotropy were examined using a highly heterogeneous finite element model of an adult male subject constructed from segmented magnetic resonance images. A total of 23 different tissue types were identified in the whole torso. The myocardial fibre orientations in the human heart wall were mapped from the fibre orientations of a canine heart which are available in the literature using deformable mapping techniques. The current and potential distributions in the whole torso were computed using dipolar sources in the septum, apical area, left ventricular wall or right ventricular wall. For each dipole x, y, z orientations were studied. An adaptive finite element solver was used to compute currents and potential distributions in the whole torso with an element size of 0.78 x 0.78 x 3 mm in the myocardium and larger elements in other parts of the torso. For each dipole position two cases were studied. In one case the myocardium was isotropic and in the other it was anisotropic. It was found that BSPMs showed a very notable difference between the isotropic and the anisotropic myocardium for all dipole positions with the largest difference for the apical dipoles. The correlation coefficients for the BSPMs between the isotropic and anisotropic cases ranged from 0.83 for an apical dipole to 0.99 for an RV wall dipole. These results suggest that myocardial fibre anisotropy plays an important role in determining the body surface potentials.

Adult↗
PubMed2001

A locus for autosomal dominant hereditary spastic ataxia, SAX1, maps to chromosome 12p13.

The hereditary spastic ataxias (HSA) are a group of clinically heterogeneous neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia. HSA was diagnosed in three unrelated autosomal dominant families from Newfoundland, who presented mainly with severe leg spasticity, dysarthria, dysphagia, and ocular-movement abnormalities. A genomewide scan was performed on one family, and linkage to a novel locus for HSA on chromosome 12p13, which contains the as-yet-unidentified gene locus SAX1, was identified. Fine mapping confirmed linkage in the two large families, and the third, smaller family showed LOD scores suggestive of linkage. Haplotype construction by use of 13 polymorphic markers revealed that all three families share a disease haplotype, which key recombinants and overlapping haplotypes refine to about 5 cM, flanked by markers D12S93 and GATA151H05. SAX1 is the first locus mapped for autosomal dominant HSA.

Ataxia↗
PubMed1992

Assignment of the human heterogeneous nuclear ribonucleoprotein A1 gene (HNRPA1) to chromosome 12q13.1 by cDNA competitive in situ hybridization.

Heterogeneous nuclear ribonucleoprotein (HNRP) core protein A1 is a major component of mammalian HNRP particles. The human HNRP A1 protein was shown to be encoded by a 4.6-kb gene, split into 10 exons, belonging to a multigene family of about 30 A1-specific sequences per haploid genome, many of which correspond to pseudogenes of the processed type. Here we report the mapping of the human HNRPA1 gene to band 12q13.1. Localization was performed by nonisotopic in situ hybridization using a phage genomic clone that contains the active HNRPA1 gene as well as 13.5-kb flanking sequences. To suppress hybridization to pseudogene sequences, unlabeled HNRPA1 cDNA was added in excess over the probe to the hybridization mixture.

Binding, Competitive↗
PubMed2004

Further evidence of genetic heterogeneity in autosomal dominant distal motor neuronopathy.

Distal hereditary motor neuronopathy is a genetically and clinically heterogeneous disorder. To date, five loci, and their relative genes, have been mapped on chromosomes 7p14, 7q11, 9q34, 11q12 and 12q24, respectively. We describe an Italian family with autosomal dominant distal HMN starting at around 30 years of age with weakness and atrophy of distal leg muscles and pyramidal features. We performed genetic linkage analysis on chromosomes 7p14, 9q34, 11q12 and 12q24. Moreover we sequenced the genes mapped to 7q11 and 12q24. Negative LOD scores excluded linkage to 7p14, 9q34, and 11q12 chromosomes in our family. No mutations were found in genes mapped to 7q11 and 12q24. In addition, because of pyramidal features, we performed the linkage analysis to all the known loci for autosomal dominant hereditary spastic paraparesis. The analysis was negative thus excluding a complicated form of autosomal dominant hereditary spastic paraparesis. These data further confirm a genetic heterogeneity within inherited motor neuronopathy.

Adult↗
PubMed1998

Calibrated functional MRI: mapping the dynamics of oxidative metabolism.

MRI was extended to the measurement of changes in oxidative metabolism in the normal human during functionally induced changes in cellular activity. A noninvasive MRI method that is model-independent calibrates the blood oxygen level dependent (BOLD) signal of functional MRI (fMRI) against perfusion-sensitive MRI, using carbon dioxide breathing as a physiological reference standard. This calibration procedure provides a regional measurement of the expected sensitivity of the fMRI BOLD signal to changes in the cellular activity of the brain. Maps of the BOLD signal calibration factor showed regional heterogeneity, indicating that the magnitude of functionally induced changes in the BOLD signal will be dependent on both the local change in blood flow and the local baseline physiology of the cerebral cortex. BOLD signal magnitude is shown to be reduced by 32% from its expected level by the action of oxygen metabolism. The calibrated fMRI technique was applied to stimulation of the human visual cortex with an alternating radial checkerboard pattern. With this stimulus oxygen consumption increased 16% whereas blood flow increased 45%. Although this result is consistent with previous findings of a significant difference between the increase in blood flow and oxygen consumption, it does indicate clearly that oxidative metabolism is a significant component of the metabolic response of the brain to functionally induced changes in cellular activity.

Brain↗