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Biomedical subjects

E Paulesu

Publications and source records attributed to E Paulesu.

At least 19 recordsLinked to original sources
PubMed2001

Dyslexia: cultural diversity and biological unity.

The recognition of dyslexia as a neurodevelopmental disorder has been hampered by the belief that it is not a specific diagnostic entity because it has variable and culture-specific manifestations. In line with this belief, we found that Italian dyslexics, using a shallow orthography which facilitates reading, performed better on reading tasks than did English and French dyslexics. However, all dyslexics were equally impaired relative to their controls on reading and phonological tasks. Positron emission tomography scans during explicit and implicit reading showed the same reduced activity in a region of the left hemisphere in dyslexics from all three countries, with the maximum peak in the middle temporal gyrus and additional peaks in the inferior and superior temporal gyri and middle occipital gyrus. We conclude that there is a universal neurocognitive basis for dyslexia and that differences in reading performance among dyslexics of different countries are due to different orthographies.

Adult↗
PubMed2001

Acupuncture produces central activations in pain regions.

Acupuncture is largely used for pain control in several pathological conditions. Its effects on the central nervous system are not well defined. We investigated the effect of the application of acupuncture to 13 normal subjects (males, 21-32 years). H2(15)O bolus PET scans were read before the application of the needles (Rest, R) and after 25 min of needle insertion. Data were acquired by scanning in 3-D mode. The acupuncture application, true acupuncture (TA), was alternated to a placebo needle application (PA) in two different sequences (seven and six subjects, respectively), either R,PA,R, TA or R,TA,R,PA, a period of 15 min being left after every first TA or PA to allow for the recovery of basal conditions. Here we show that classic acupuncture activates the left Anterior Cingulus, the Insulae bilaterally, the Cerebellum bilaterally, the left Superior Frontal Gyrus, and the right Medial and Inferior Frontal Gyri. Most of the activated areas are shared with areas activated in acute and chronic pain states as described in the literature. Thus acupuncture appears to act by activating areas also involved in pain. This indicates that acupuncture could relief pain by unbalancing the equilibrium of distributed pain-related central networks.

Acupuncture Points↗
PubMed2001

Cerebral representations for egocentric space: Functional-anatomical evidence from caloric vestibular stimulation and neck vibration.

The internal representation of space involves the integration of different sensory inputs-visual, somatosensory/proprioceptive, vestibular-yielding reference frames which are not based on individual peripheral sensory codes, being organized instead in ego-centred (e.g. head, trunk, arm) and object- or environment-centred coordinates. Lateralized or direction-specific stimulation of peripheral sensory systems, such as caloric vestibular stimulation (CVS), posterior neck muscle mechanical vibration (NV) and optokinetic stimulation, can induce a distortion of egocentric coordinates, causing, for example, a deviation of the subjective straight ahead in pointing tasks. Appropriate forms of this stimulation can also temporarily improve a variety of pathological manifestations of unilateral neglect. We used PET measurements of regional cerebral blood flow changes in normal volunteers to measure the brain responses shared by CVS and NV. We show that somatosensory areas of the perisylvian cortex including the insula and retroinsular cortex, the temporoparietal junction and somatosensory area II receive signals from both sensory channels. We propose that these anatomical sites contribute to egocentric representation of space.

Adult↗
PubMed2001

Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks.

The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-gamma-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [18F]fluoro-deoxy-D-glucose ([18F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [18F]FDG and water may provide complementary information in pharmacodynamic studies.

Adult↗
PubMed2000

A cultural effect on brain function.

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.

Adult↗
PubMed1999

A multiparametric MRI study of frontal lobe dementia in multiple sclerosis.

Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2- and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2- and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P=0.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.

Dementia↗
PubMed1999

Rapid assessment of regional cerebral metabolic abnormalities in single subjects with quantitative and nonquantitative [18F]FDG PET: A clinical validation of statistical parametric mapping.

The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion studies.

Adolescent↗
PubMed1999

Pathways of interhemispheric transfer in normals and in a split-brain subject. A positron emission tomography study.

We studied with PET the intra- and interhemispheric pathways subserving a simple, speeded-up visuomotor task. Six normal subjects and one patient with a complete section of the corpus callosum (M.E.) underwent regional cerebral blood flow (rCBF) measurements under conditions of lateralized tachistoscopic visual presentations in a simple manual reaction time paradigm. Confirming previous behavioural findings, we found that on average crossed hand and/or hemifield conditions, i.e. those requiring an interhemispheric transfer of information, yielded a longer RT than uncrossed conditions. This difference (0.7 ms) was dramatically larger (45.6 ms) in the callosum-sectioned patient M.E. In normal subjects the cortical areas selectively activated in uncrossed and crossed conditions were different. In the former condition, most activation foci were anterior to the ventral anterior commissure (VAC) plane, whereas in the latter there was a prevalent parietal and occipital activation. This shows that a simple model in which the cortical visuo-motor pathways are similar in the intra- and the interhemispheric condition, with an extra callosal route for the latter, is too simplistic. Furthermore, these results suggest that the bulk of visuomotor interhemispheric transfer takes place through the widespread callosal fibres interconnecting the parietal cortices of the two hemispheres. The pattern of activation in the two crossing conditions was markedly different in M.E., in whom interhemispheric transfer might take place via his intact anterior commissure or subcortical commissures.

Adult↗
PubMed1998

Recovery of neglect after right hemispheric damage: H2(15)O positron emission tomographic activation study.

BACKGROUND: The neural correlates of recovery of unilateral neglect (ULN), as well as of other consequences of focal brain damage, are largely unknown. Functional neuroimaging methods (in particular, positron emission tomography [PET]) can be applied to the in vivo study of recovery mechanisms in neurologic patients. OBJECTIVE: To evaluate the functional cerebral correlates of recovery from ULN in patients with right-sided lesions, with the use of a PET activation paradigm. METHODS: Study of 3 patients with cerebrovascular lesions that involved corticosubcortical (patient 1) or subcortical (patients 2 and 3) areas of the right hemisphere. Unilateral neglect was tested twice, before and after completion of a 2-month rehabilitation program, after which all 3 patients showed considerable improvement. Similarly, 2 PET examinations were performed, before and after recovery, during the performance of a visuospatial task requiring the patients to detect and respond to visual targets moving on a computer screen from the right to the left visual hemifield (experimental condition). The cerebral activation was compared with a baseline task in which subjects responded to a black dot flashing in a fixed position of the right hemifield. RESULTS: The brain areas activated by the performance of the visuospatial task before and after recovery were compared. In all 3 patients, the regions notably more active after recovery were almost exclusively found in right-sided cortical areas and largely overlapped with those observed in a group of 4 normal subjects performing the same task. Other areas, which have been shown to be involved in attentional and oculomotor tasks in other PET studies, were also activated in patients with ULN. CONCLUSIONS: The behavioral recovery of ULN in these patients with predominantly subcortical lesions is mainly associated with cerebral activations in cortical regions similar to those observed in normal subjects. There is some evidence of functional reorganization in individual subjects, which involves other areas related to space representation and exploration.

Aged↗
PubMed1998

Differential distribution of striatal [123I]beta-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography.

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P<0. 0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3" caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [123I]beta-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP.

Aged↗
PubMed1998

The bilingual brain. Proficiency and age of acquisition of the second language.

Functional imaging methods show differences in the pattern of cerebral activation associated with the subject's native language (L1) compared with a second language (L2). In a recent PET investigation on bilingualism we showed that auditory processing of stories in L1 (Italian) engages the temporal lobes and temporoparietal cortex more extensively than L2 (English). However, in that study the Italian subjects learned L2 late and attained a fair, but not an excellent command of this language (low proficiency, late acquisition bilinguals). Thus, the different patterns of activation could be ascribed either to age of acquisition or to proficiency level. In the current study we use a similar paradigm to evaluate the effect of early and late acquisition of L2 in highly proficient bilinguals. We studied a group of Italian-English bilinguals who acquired L2 after the age of 10 years (high proficiency, late acquisition bilinguals) and a group of Spanish-Catalan bilinguals who acquired L2 before the age of 4 years (high proficiency, early acquisition bilinguals). The differing cortical responses we had observed when low proficiency volunteers listened to stories in L1 and L2 were not found in either of the high proficiency groups in this study. Several brain areas, similar to those observed for L1 in low proficiency bilinguals, were activated by L2. These findings suggest that, at least for pairs of L1 and L2 languages that are fairly close, attained proficiency is more important than age of acquisition as a determinant of the cortical representation of L2.

Adult↗
PubMed1997

Anatomical variability in the cortical representation of first and second language.

Functional magnetic resonance imaging was used to assess inter-subject variability in the cortical representation of language comprehension processes. Moderately fluent French-English bilinguals were scanned while they listened to stories in their first language (L1 = French) or in a second language (L2 = English) acquired at school after the age of seven. In all subjects, listening to L1 always activated a similar set of areas in the left temporal lobe, clustered along the left superior temporal sulcus. Listening to L2, however, activated a highly variable network of left and right temporal and frontal areas, sometimes restricted only to right-hemispheric regions. These results support the hypothesis that first language acquisition relies on a dedicated left-hemispheric cerebral network, while late second language acquisition is not necessarily associated with a reproducible biological substrate. The postulated contribution of the right hemisphere to L2 comprehension is found to hold only on average, individual subjects varying from complete right lateralization to standard left lateralization for L2.

Adult↗
PubMed1997

Functional heterogeneity of left inferior frontal cortex as revealed by fMRI.

Using functional magnetic resonance imaging (fMRI), we mapped brain activity in six normal volunteers during two silent verbal fluency tasks, one with a phonemic (letter) cue and one with a semantic (category) cue. In comparison with resting state, both tasks activated the anterior triangular portion of the left inferior frontal gyrus (IFG or F3, for third frontal gyrus) and the left thalamus. There were also areas activated in one task but not in the other: the posterior opercular portion of the left IFG for phonemic fluency, and the left retrosplenial region for semantic fluency. Our findings concur with normal psychophysical data and neuropsychological observations to suggest the recruitment of two overlapping but dissociable systems for the two tasks, and demonstrate functional heterogeneity within the left IFG (Broca's area), where the opercular portion is responsible for obtaining access to words through a phonemic/articulatory route.

Adult↗
PubMed1996

Brain activity during stimulus independent thought.

The neural correlates of stimulus-independent thoughts (SITs) were investigated in two studies of normal volunteers, using positron emission tomography (PET) and H2(15)O to measure regional cerebral blood flow. Subjects rated how frequently SITs occurred while they were concurrently performing different sets of cognitive tasks. In both studies, the main positive correlations between SITs and blood flow were in the medial prefrontal region. These correlations were not attributable to between-task differences in cognitive demand, or to effects of practice on these demands. An association between medial prefrontal activity and SITs is consistent with data linking this region to self-initiated thought, and its activation during tasks which entail thinking which is decoupled from stimuli in the immediate environment.

Adult↗
PubMed1996

Silent ischemia as a central problem: regional brain activation compared in silent and painful myocardial ischemia.

OBJECTIVE: To test whether the silence of painless myocardial ischemia is caused by abnormal handling by the central nervous system of afferent messages from the heart. DESIGN: Nonrandomized study. SETTING: A tertiary referral center (postgraduate medical school). PATIENTS: 2 matched groups of nondiabetic patients with coronary artery disease. Group A consisted of nine patients with reproducible stress-induced angina; group B consisted of nine patients with reproducible stress-induced myocardial ischemia but no angina. INTERVENTIONS: Intravenous placebo infusion and low-dose (5 and 10 micrograms/ kg per minute) and high-dose (20 to 35 micrograms/kg per minute) dobutamine infusions. MEASUREMENTS: Positron emission tomography was used to measure regional cerebral blood flow changes as an index of neuronal activation during painful and silent myocardial ischemia induced by intravenous dobutamine. RESULTS: Regional cerebral blood flow changes during myocardial ischemia were compared with those during baseline conditions and during placebo infusion. During myocardial ischemia, regional cerebral blood flow increased bilaterally in the thalami and prefrontal, basal frontal, and ventral cingulate corticles in patients in group A. Both thalami were activated in group B, but cortical activation was limited to the right frontal region. A formal comparison of groups A and B showed significant differences (P < 0.01) in activation of the basal frontal cortex, ventral cingulate cortex, and left temporal pole. In both groups, thalamic regional cerebral blood flow remained increased after the symptoms and signs of ischemia had ceased. CONCLUSIONS: Bilateral activation of the thalamus can be shown in both angina and silent ischemia; thus, peripheral nerve dysfunction cannot completely explain silent ischemia. Frontal cortical activation appears to be necessary for the sensation of pain. Abnormal central processing of afferent pain messages from the heart may play a determining role in silent myocardial ischemia.

Afferent Pathways↗
PubMed1996

PET Studies of Phonological Processing: A Critical Reply to Poeppel

Poeppel (1996) raises a number of criticisms about the methods and reported results for eight studies of phonological processing from six different neuroimaging laboratories. We would freely admit that valid criticisms of PET methodology can be made and that, like any method, it has limitations; in fact, we and others have engaged in such critical commentary (Steinmetz & Seitz, 1991; Sergent et al., 1992; Demonet, 1995; Fiez et al., 1996a; Zatorre et al., 1996). Poeppel's analysis, though, falls far short of providing new insights into the limitations of PET methodology or the means by which future functional imaging studies could be improved. Many of Poeppel's criticisms derive from a failure to understand some of the fundamental issues which motivate functional imaging studies, including those he reviews. However, we are grateful to our critic inasmuch as he offers us the challenge to clarify our positions on important aspects of our experimental design, analysis, and interpretation. In our discussion of these issues, we begin with a general commentary, followed by specific comments from individual authors.

Journal Article↗
PubMed1996

Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study.

Structural neuroimaging has been used to correlate lesional patterns with the cognitive profile of patients with multiple sclerosis (MS), especially for "frontal" dysfunction. However, a clear-cut anatomical explanation has yet to be found for the long-term memory deficit which is a hallmark of MS cognitive impairment. We have used PET to measure regional cerebral glucose metabolism (rCMRglc) in a group of 15 MS patients with involvement of verbal and/or spatial long-term memory. These patients were compared with 10 normal controls and 13 MS patients unimpaired on all neuropsychological tests. Relative to the controls, MS patients with memory deficits showed a significant bilateral reduction of rCMRglc in the hippocampus, cingulate gyrus, thalamus, associative occipital cortex, and cerebellum. Direct comparisons between patients with memory deficits and the group of unimpaired MS patients showed a metabolic reduction in the left thalamus and in both hippocampi. Seven of the memory-impaired patients also had neuropsychological signs of frontal dysfunction. These patients were compared with patients who had isolated memory deficit. Here we observed a further metabolic reduction in a number of brain regions including bilateral prefrontal cortex, inferior parietal cortex, and basal ganglia. Our findings indicate that hypometabolism of thalamic and deep cortical gray structures of the temporal lobe is associated with episodic memory dysfunction in MS. On the other hand, pathological performance on tests designed to assess frontal functions was associated with widespread reduction of glucose metabolism.

Adult↗