Brodmann Area (brodmann + area)

Distribution by Scientific Domains


Selected Abstracts


Alterations in Brain Serotonin Synthesis in Male Alcoholics Measured Using Positron Emission Tomography

ALCOHOLISM, Issue 2 2009
Masami Nishikawa
Background:, A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release. Methods:, The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer ,-[11C]-methyl- l -tryptophan. Results:, Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala. Conclusions:, Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation. [source]


The essential role of Broca's area in imitation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2003
Marc Heiser
Abstract The posterior sector of Broca's area (Brodmann area 44), a brain region critical for language, may have evolved from neurons active during observation and execution of manual movements. Imaging studies showing increased Broca's activity during execution, imagination, imitation and observation of hand movements support this hypothesis. Increased Broca's activity in motor task, however, may simply be due to inner speech. To test whether Broca's area is essential to imitation, we used repetitive transcranial magnetic stimulation (rTMS), which is known to transiently disrupt functions in stimulated areas. Subjects imitated finger key presses (imitation) or executed finger key presses in response to spatial cues (control task). While performing the tasks, subjects received rTMS over the left and right pars opercularis of the inferior frontal gyrus (where Brodmann area 44 is probabilistically located) and over the occipital cortex. There was significant impairment in imitation, but not in the control task, during rTMS over left and right pars opercularis compared to rTMS over the occipital cortex. This suggests that Broca's area is a premotor region essential to finger movement imitation. [source]


Prefrontal and agranular cingulate projections to the dorsal premotor areas F2 and F7 in the macaque monkey

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003
Giuseppe Luppino
Abstract The superior sector of Brodmann area 6 (dorsal premotor cortex, PMd) of the macaque monkey consists of a rostral and a caudal architectonic area referred to as F7 and F2, respectively. The aim of this study was to define the origin of prefrontal and agranular cingulate afferents to F7 and F2, in the light of functional and hodological evidence showing that these areas do not appear to be functionally homogeneous. Different sectors of F7 and F2 were injected with neural tracers in seven monkeys and the retrograde labelling was qualitatively and quantitatively analysed. The dorsorostral part of F7 (supplementary eye field, F7-SEF) was found to be a target of strong afferents from the frontal eye field (FEF), from the dorsolateral prefrontal regions located dorsally (DLPFd) and ventrally (DLPFv) to the principal sulcus and from cingulate areas 24a, 24b and 24c. In contrast, the remaining part of F7 (F7-non SEF) is only a target of the strong afferents from DLPFd. Finally, the ventrorostral part of F2 (F2vr), but not the F2 sector located around the superior precentral dimple (F2d), receives a minor, but significant, input from DLPFd and a relatively strong input from the cingulate gyrus (areas 24a and 24b) and area 24d. Present data provide strong hodological support in favour of the idea that areas F7 and F2 are formed by two functionally distinct sectors. [source]


Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-, activity

GENES, BRAIN AND BEHAVIOR, Issue 4 2010
F. Benedetti
At the crossroad of multiple pathways regulating trophism and metabolism, glycogen synthase kinase (GSK)3 is considered a key factor in influencing the susceptibility of neurons to harmful stimuli (neuronal resilience) and is a target for several psychiatric drugs that directly inhibit it or increase its inhibitory phosphorylation. Inhibition of GSK3 prevents apoptosis and could protect against the neuropathological processes associated with psychiatric disorders. A GSK3- ,promoter single-nucleotide polymorphism (rs334558) influences transcriptional strength, and the less active form was associated with less detrimental clinical features of mood disorders. Here we studied the effect of rs334558 on grey matter volumes (voxel-based morphometry) of 57 patients affected by chronic schizophrenia. Carriers of the less active C allele variant showed significantly higher brain volumes in an area encompassing posterior regions of right middle and superior temporal gyrus, within the boundaries of Brodmann area 21. The temporal lobe is the brain parenchymal region with the most consistently documented morphometric abnormalities in schizophrenia, and neuropathological processes in these regions develop soon at the beginning of the illness. These results support the interest for GSK3- ,as a factor affecting neuropathology in major behavioural disorders, such as schizophrenia, and thus as a possible target for treatment. [source]


Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms

HUMAN BRAIN MAPPING, Issue 5 2009
Gaelle Bettus
Abstract A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms. Hum Brain Mapp 2009. © 2008 Wiley-Liss, Inc. [source]


A developmental fMRI study of self-regulatory control

HUMAN BRAIN MAPPING, Issue 11 2006
Rachel Marsh
Abstract We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of self-regulatory control across development in healthy individuals performing the Stroop interference task. Proper performance of the task requires the engagement of self-regulatory control to inhibit an automatized response (reading) in favor of another, less automatic response (color naming). Functional MRI scans were acquired from a sample of 70 healthy individuals ranging in age from 7 to 57 years. We measured task-related regional signal changes across the entire cerebrum and conducted correlation analyses to assess the associations of signal activation with age and with behavioral performance. The magnitude of fMRI signal change increased with age in the right inferolateral prefrontal cortex (Brodmann area [BA] 44/45) and right lenticular nucleus. Greater activation of the right inferolateral prefrontal cortex also accompanied better performance. Activity in the right frontostriatal systems increased with age and with better response inhibition, consistent with the known functions of frontostriatal circuits in self-regulatory control. Age-related deactivations in the mesial prefrontal cortex (BA 10), subgenual anterior cingulate cortex (BA 24), and posterior cingulate cortex (BA 31) likely represented the greater engagement of adults in self-monitoring and free associative thought processes during the easier baseline task, consistent with the improved performance on this task in adults compared with children. Although we cannot exclude the possibility that age-related changes in reading ability or in the strategies used to optimize task performance were responsible for our findings, the correlations of brain activation with performance suggest that changes in frontostriatal activity with age underlie the improvement in self-regulatory control that characterizes normal human development. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc. [source]


Temporal dynamics of ipsilateral and contralateral motor activity during voluntary finger movement

HUMAN BRAIN MAPPING, Issue 1 2004
Ming-Xiong Huang
Abstract The role of motor activity ipsilateral to movement remains a matter of debate, due in part to discrepancies among studies in the localization of this activity, when observed, and uncertainty about its time course. The present study used magnetoencephalography (MEG) to investigate the spatial localization and temporal dynamics of contralateral and ipsilateral motor activity during the preparation of unilateral finger movements. Eight right-handed normal subjects carried out self-paced finger-lifting movements with either their dominant or nondominant hand during MEG recordings. The Multi-Start Spatial Temporal multi-dipole method was used to analyze MEG responses recorded during the movement preparation and early execution stage (,800 msec to +30 msec) of movement. Three sources were localized consistently, including a source in the contralateral primary motor area (M1) and in the supplementary motor area (SMA). A third source ipsilateral to movement was located significantly anterior, inferior, and lateral to M1, in the premotor area (PMA) (Brodmann area [BA] 6). Peak latency of the SMA and the ipsilateral PMA sources significantly preceded the peak latency of the contralateral M1 source by 60 msec and 52 msec, respectively. Peak dipole strengths of both the SMA and ipsilateral PMA sources were significantly weaker than was the contralateral M1 source, but did not differ from each other. Altogether, the results indicated that the ipsilateral motor activity was associated with premotor function, rather than activity in M1. The time courses of activation in SMA and ipsilateral PMA were consistent with their purported roles in planning movements. Hum. Brain Mapp. 23:26,39, 2004. © 2004 Wiley-Liss, Inc. [source]


Feature uncertainty activates anterior cingulate cortex,

HUMAN BRAIN MAPPING, Issue 1 2004
Szabolcs Kéri
Abstract In visual discrimination tasks, the relevant feature to discriminate is defined before stimulus presentation. In feature uncertainty tasks, a cue about the relevant feature is provided after stimulus offset. We used 15O-butanol positron emission tomography (PET) in order to investigate brain activation during a feature uncertainty task. There was greater activity during the feature uncertainty task, compared with stimulus detection and discrimination of orientation and spatial frequency, in the lateral and medial prefrontal cortex, the cuneus, superior temporal and inferior parietal cortex, cortical motor areas, and the cerebellum. The most robust and consistent activation was observed in the dorsal anterior cingulate cortex (Brodmann area 32; x = 0 y = 16, z = 40). The insula, located near the claustrum (x = ,38, y = 8, z = 4), was activated during the discrimination tasks compared with the feature uncertainty condition. These results suggest that the dorsal anterior cingulate cortex is important in feature uncertainty conditions, which include divided attention, expectancy under uncertainty, and cognitive monitoring. Hum. Brain Mapp. 21:26,33, 2004. © 2003 Wiley-Liss, Inc. [source]


A proteome analysis of the dorsolateral prefrontal cortex in human alcoholic patients

PROTEOMICS - CLINICAL APPLICATIONS, Issue 1 2007
Kimberley Alexander-Kaufman
Abstract Alcoholic patients commonly experience cognitive decline. It is postulated that cognitive dysfunction is caused by an alcohol-induced region-selective brain damage, particularly to the prefrontal region, and grey and white matter may be affected differently. We used a proteomics-based approach to compare protein expression profiles of the dorsolateral prefrontal cortex (Brodmann area 9 (BA9)) from human alcoholic and healthy control brains. Changes in the relative expression of 110 protein 'spots' were identified in the BA9 grey matter, of which 54 were identified as 44 different proteins. In our recent article, 60 protein spots were differentially expressed in the BA9 white matter and 18 of these were identified (Alexander-Kaufman, K., James, G., Sheedy, D., Harper, C., Matsumoto, I., Mol. Psychiatry 2006, 11, 56-65). Additional BA9 white matter proteins are identified here and discussed in conjunction to our grey matter results. Thiamine-dependent enzymes transketolase and pyruvate dehydrogenase (E1, ubunit) were among the proteins identified. To our knowledge, this is the first time a disruption in thiamine-dependent enzymes has been demonstrated in the brains of ,neurologically uncomplicated' alcoholics. By identifying protein expression changes in prefrontal grey and white matter separately, hypotheses may draw upon more mechanistic explanations as to how alcoholism causes the structural alterations associated with alcohol-related brain damage and cognitive dysfunction. [source]


Attenuated prefrontal activation during a verbal fluency task in remitted major depression

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2009
Go Okada md
The aim of the present study was to investigate whether a functional abnormality in the left prefrontal cortex observed in patients with major depression performing a verbal fluency task is present after remission of depression. Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in eight remitted patients with major depression and 10 healthy control subjects during a verbal fluency task. Compared to the control subjects, the patients had a reduced response in the left prefrontal cortex (middle frontal gyrus, Brodmann area 10). These findings suggest the presence of dysfunction in the left prefrontal cortex during remission in major depression. [source]


The graphemic/motor frontal area Exner's area revisited,

ANNALS OF NEUROLOGY, Issue 4 2009
Franck-Emmanuel Roux MD
Objective In 1881, Exner first described a "graphic motor image center" in the middle frontal gyrus. Current psycholinguistic models of handwriting involve the conversion of abstract, orthographic representations into motor representations before a sequence of appropriate hand movements is produced. Direct cortical stimulation and functional magnetic resonance imaging (fMRI) were used to study the human frontal areas involved in writing. Methods Cortical electrical stimulation mapping was used intraoperatively in 12 patients during the removal of brain tumors to identify the areas involved in oral language (sentence reading and naming) and writing, and to spare them during surgery. The fMRI activation experiment involved 12 right-handed and 12 left-handed healthy volunteers using word dictation (without visual control) and 2 control tasks. Results Direct cortical electrical stimulation of restricted areas rostral to the primary motor hand area (Brodmann area [BA] 6) impaired handwriting in 6 patients, without disturbing hand movements or oral language tasks. In 6 other patients, stimulation of lower frontal regions showed deficits combining handwriting with other language tasks. fMRI also revealed selective activation during word handwriting in left versus right BA6 depending on handedness. This area was anatomically matched to those areas that affected handwriting on electrical stimulation. Interpretation An area in middle frontal gyrus (BA6) that we have termed the graphemic/motor frontal area supports bridging between orthography and motor programs specific to handwriting. Ann Neurol 2009;66:537,545 [source]


Coupling of theta activity and glucose metabolism in the human rostral anterior cingulate cortex: An EEG/PET study of normal and depressed subjects

PSYCHOPHYSIOLOGY, Issue 6 2003
Diego A. Pizzagalli
Abstract In rodents, theta rhythm has been linked to the hippocampal formation, as well as other regions, including the anterior cingulate cortex (ACC). To test the role of the ACC in theta rhythm, concurrent measurements of brain electrical activity (EEG) and glucose metabolism (PET) were performed in 29 subjects at baseline. EEG data were analyzed with a source localization technique that enabled voxelwise correlations of EEG and PET data. For theta, but not other bands, the rostral ACC (Brodmann areas 24/32) was the largest cluster with positive correlations between current density and glucose metabolism. Positive correlations were also found in right fronto-temporal regions. In control but not depressed subjects, theta within ACC and prefrontal/orbitofrontal regions was positively correlated. The results reveal a link between theta and cerebral metabolism in the ACC as well as disruption of functional connectivity within frontocingulate pathways in depression. [source]


Preoperative Functional Assessment of Auditory Cortex in Adult Cochlear Implant Users,,

THE LARYNGOSCOPE, Issue 1 2001
Peter S. Roland MD
Abstract Objectives To e-plore functional neuroanatomical responses to auditory stimulation before and after implantation. Study Design A prospective study of three cochlear implant candidates (pure-tone averages of 90 dB HL or greater bilaterally and hearing in noise test [HINT] performances of <40%) in which regional cerebral blood flow (rCBF) was assessed using single photon emission computed tomography (SPECT). Methods Candidates watched a 15-minute videotaped story under four conditions: audio presented monaurally in the right and left ears (aided), audio presented binaurally (aided), and visual-only presentation of the story. Five minutes into each story, 20 to 25 mCi of technetium 99m (99mTc) hexamethyl-propyleneamine-oxime (HMPAO) (Ceratec; Nycomed Amersham, Princeton, NJ, U.S.A.) was injected over a 30-second period to ensure that subjects were unaware of tracer administration. Subjects were scanned for 20 minutes using a PRISM 3000 gamma camera (Picker International, Cleveland, OH, U.S.A.). Data were normalized and co-registered, and subtraction images were compiled. Subtraction images contrasted activation patterns generated under the visual-only control condition to the auditory activation states acquired monaurally and binaurally. Results Right and left ear monaural stimulation in normal hearing subjects resulted in significant bilateral activation of Brodmann areas 41, 42, 21, 22, and 38. Although substantial intersubject response variability was noted, subjects generally failed to bilaterally activate these areas under monaural hearing aid presentations; however, bilateral activation of areas 41 and 22 was noted under binaural presentations. Conclusions Despite relatively similar hearing losses in each ear, significant differences in preoperative auditory corte- activation were observed between ears. These data suggest that functional brain imaging provides a useful tool for e-ploring the responsiveness of the auditory corte- in cochlear implant candidates. [source]


Plasticity of language networks in patients with brain tumors: A positron emission tomography activation study

ANNALS OF NEUROLOGY, Issue 5 2001
Alexander Thiel MD
We investigated plasticity of language networks exposed to slowly evolving brain damage. Single subject O-15-water language activation positron emission tomography studies were analyzed in 61 right-handed patients with brain tumors of the left hemisphere, and 12 normal controls. In controls, activations were found in left Brodmann's Area (BA)44 and BA45, superior posterior temporal gyrus bilaterally, and right cerebellum. Patients additionally activated left BA46, BA47, anterior insula, and left cerebellum. Superior temporal activation was less frequent, and activations in areas other than posterior temporal gyrus were found bilaterally. Frontolateral activations within the nondominant hemisphere were only seen in patients (63%) with frontal or posterior temporal lesions. Laterality indices of frontolateral cortex showed reversed language dominance in 18% of patients. Laterality indices of the cerebellum were negatively correlated with language performance. Two compensatory mechanisms in patients with slowly evolving brain lesions are described: An intrahemispheric mechanism with recruitment of left frontolateral regions other than classic language areas; and an interhemispheric compensatory mechanism with frontolateral activation in the nondominant hemisphere. The latter one was only found in patients with frontal or posterior temporal lesions, thus supporting the hypothesis that right frontolateral activations are a disinhibition phenomenon. [source]


Novel putative nonprotein-coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophrenia

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2003
Oxana O. Polesskaya
Abstract A modified method of differential display was employed to identify a novel gene (named PSZA11q14), the expression of which was reduced in brains from patients with schizophrenia. Decreased expression of PSZA11q14 was identified initially in Brodmann's area (BA) 21 from a small group of patients with schizophrenia (n = 4) and normal controls (n = 6) and was confirmed subsequently using independent RT-PCR assay in BA 21, 22, and 9, and in hippocampus from a larger group of patients with schizophrenia (n = 36) and controls (n = 35). PSZA11q14 is located on chromosome 11q14, an area shown previously to co-segregate with schizophrenia and related disorders in several families. Decreased expression of PSZA11q14 in patients with schizophrenia and its location on 11q14 provide converging lines of evidence indicating that PSZA11q14 may be involved in at least some cases of schizophrenia. PSZA11q14 shows no significant homology with any known gene. It has no introns and produces two RNA transcripts of ,4.5 and ,7.0 kb. The largest open reading frame (ORF) in the PSZA11q14 transcripts may potentially encode for a short polypeptide of 71 amino acids. High frequency of rare codons, the short size of this ORF, and low homology with mouse sequences, however, indicate that PSZA11q14 may instead represent a novel member of a family of nonprotein-coding RNA genes that are not translated and that function at the RNA level. PSZA11q14 is located within the first intron of the DLG-2 gene and transcribed in the opposite direction to DLG-2. These results suggest that PSZA11q14 may be considered a candidate gene for schizophrenia acting as an antisense regulator of DLG-2, which controls assembling functional N -methyl- D -aspartate (NMDA) receptors. © 2003 Wiley-Liss, Inc. [source]


Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: A functional MRI case study

MOVEMENT DISORDERS, Issue 12 2003
Taresa Stefurak MD
Abstract Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta). © 2003 Movement Disorder Society [source]


Variability of Broca's area homologue in African great apes: Implications for language evolution

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2003
Chet C. Sherwood
Abstract The cortical circuits subserving neural processing of human language are localized to the inferior frontal operculum and the posterior perisylvian region. Functional language dominance has been related to anatomical asymmetry of Broca's area and the planum temporale. The evolutionary history of these asymmetric patterns, however, remains obscure. Although testing of hypotheses about the evolution of language areas requires comparison to homologous regions in the brains of our closest living relatives, the great apes, to date little is known about normal interindividual variation of these regions in this group. Here we focus on Brodmann's area 44 in African great apes (Pan troglodytes and Gorilla gorilla). This area corresponds to the pars opercularis of the inferior frontal gyrus (IFG), and has been shown to exhibit both gross and cytoarchitectural asymmetries in humans. We calculated frequencies of sulcal variations and mapped the distribution of cytoarchitectural area 44 to determine whether its boundaries occurred at consistent macrostructural landmarks. A considerable amount of variation was found in the distribution of the inferior frontal sulci among great ape brains. The inferior precentral sulcus in particular was often bifurcated, which made it impossible to determine the posterior boundary of the pars opercularis. In addition, the distribution of Brodmann's area 44 showed very little correspondence to surface anatomy. We conclude that gross morphologic patterns do not offer substantive landmarks for the measurement of Brodmann's area 44 in great apes. Whether or not Broca's area homologue of great apes exhibits humanlike asymmetry can only be resolved through further analyses of microstructural components. Anat Rec Part A 271A:276,285, 2003. © 2003 Wiley-Liss, Inc. [source]