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Biomedical subjects

E Paulesu

Publications and source records attributed to E Paulesu.

At least 19 recordsLinked to original sources

Left caloric vestibular stimulation ameliorates right hemianesthesia.

BACKGROUND: Left caloric vestibular stimulation (CVS) transiently reduces impairments of right-brain-damaged patients with left unilateral neglect, including left hemianesthesia, contralateral to the side of the lesion (contralesional). Conversely, no effect on right contralesional hemianesthesia in left-brain-damaged patients is seen with right CVS. This discrepancy is unexplained. METHODS: The authors explored the effect of CVS on right- and left-brain-damaged patients with hemianesthesia. One left-brain-damaged patient had an fMRI study during tactile stimulation before and after left CVS. The same fMRI touch study, without CVS, was performed in neurologically unimpaired subjects. RESULTS: A transient remission of right hemianesthesia associated with left brain damage was observed, provided that cold CVS was administered to the left ear. In the left-brain-damaged patient studied with fMRI, left CVS modulated the neural response to right hand tactile stimuli of a portion of the secondary somatosensory area (SII) of the right hemisphere. In neurologically unimpaired subjects, fMRI scans showed that the same part of area SII in the right hemisphere was activated by ipsilateral right-sided touches and to a larger extent than area SII in the left hemisphere by left-sided touches. CONCLUSIONS: Left caloric vestibular stimulation is effective on both left and right hemianesthesia because it modulates the hemisphere that has a more complete representation of, or is capable to attend to, the whole somatosensory surface of the body. These results suggest a hardwired hemispheric asymmetry in hand representation, starting from a somatotopically organized brain region such as area SII.

Adult↗

Shared cortical anatomy for motor awareness and motor control.

In everyday life, the successful monitoring of behavior requires continuous updating of the effectiveness of motor acts; one crucial step is becoming aware of the movements one is performing. We studied the anatomical distribution of lesions in right-brain-damaged hemiplegic patients, who obstinately denied their motor impairment, claiming that they could move their paralyzed limbs. Denial was associated with lesions in areas related to the programming of motor acts, particularly Brodmann's premotor areas 6 and 44, motor area 4, and the somatosensory cortex. This association suggests that monitoring systems may be implemented within the same cortical network that is responsible for the primary function that has to be monitored.

Adult↗

Brain abnormalities underlying altered activation in dyslexia: a voxel based morphometry study.

Voxel-based morphometry was used to assess the consistency among functional imaging and brain morphometry data in developmental dyslexia. Subjects, from three different cultural contexts (UK, France and Italy), were the same as those described in a previous PET activation paper, which revealed a common pattern of reduced activation during reading tasks in the left temporal and occipital lobes. We provide evidence that altered activation observed within the reading system is associated with altered density of grey and white matter of specific brain regions, such as the left middle and inferior temporal gyri and the left arcuate fasciculus. This supports the view that dyslexia is associated with both local grey matter dysfunction and with altered connectivity among phonological/reading areas. The differences were replicable across samples confirming that the neurological disorder underlying dyslexia is the same across the cultures investigated in the study.

Adult↗

Brain activity during intra- and cross-modal priming: new empirical data and review of the literature.

A positron emission tomography (PET) study was conducted to investigate the neurofunctional correlate of auditory within-modality and auditory-to-visual cross-modality stem completion priming. Compared to the auditory-to-auditory priming condition, cross-modality priming was associated with a significantly larger regional cerebral blood flow (rCBF) decrease at the boundary between left inferior temporal and fusiform gyri, brain regions previously associated with modality independent lexical retrieval and reading. Instead, within-modality auditory priming was associated with a bilateral pattern of prefrontal rCBF increase. This was likely the expression of more efficient access to output lexical representations and involuntary retrieval of the recent episode during which the just generated word had been encountered.

Acoustic Stimulation↗

A functional-anatomical model for lipreading.

Regional cerebral blood flow (rCBF) PET scans were used to study the physiological bases of lipreading, a natural skill of extracting language from mouth movements, which contributes to speech perception in everyday life. Viewing connected mouth movements that could not be lexically identified and that evoke perception of isolated speech sounds (nonlexical lipreading) was associated with bilateral activation of the auditory association cortex around Wernicke's area, of left dorsal premotor cortex, and left opercular-premotor division of the left inferior frontal gyrus (Broca's area). The supplementary motor area was active as well. These areas have all been implicated in phonological processing, speech and mouth motor planning, and execution. In addition, nonlexical lipreading also differentially activated visual motion areas. Lexical access through lipreading was associated with a similar pattern of activation and with additional foci in ventral- and dorsolateral prefrontal cortex bilaterally and in left inferior parietal cortex. Linear regression analysis of cerebral blood flow and proficiency for lexical lipreading further clarified the role of these areas in gaining access to language through lipreading. The results suggest cortical activation circuits for lipreading from action representations that may differentiate lexical access from nonlexical processes.

Adult↗

Preserved functional competence of perilesional areas in drug-resistant epilepsy with lesion in supplementary motor cortex: fMRI and neuropsychological observations.

We report a presurgical fMRI study and a longitudinal behavioral and structural MRI study in a 26-year-old right-handed woman with drug-resistant epilepsy of the supplementary motor region with cytoarchitectural dysplasia and minimal cortico-subcortical gliotic damage. fMRI scans were acquired during a silent phonemic verbal fluency task (VF), an automatic counting task (CT), and a finger-tapping motor task (MT). These were all compared with rest. Presurgical neuropsychological assessment was substantially normal with only a minor deficit in the domain of visuo-constructive and complex motor-planning skills. Noticeably, performance on phonemic verbal fluency was normal. Presurgical fMRI results revealed a normal specialization of left SMA and pre-SMA, including a fine-grained somatotopy for mouth and hand representations despite epilepsy. Immediately after surgical removal of the epileptogenic zone (the posterior third of the superior and middle frontal gyri including pre-SMA and part of SMA, and part of the anterior cingulate region--all of which were active presurgically at the fMRI tests), the patient suffered from transcortical motor aphasia temporarily. One year after surgery, she still showed impaired performance in the verbal fluency tasks while naming and comprehension were recovered. The patient was now free from seizures. This fMRI study supports the case that repeated seizures per se may not be sufficient to alter the distribution of neural representations of cognitive function. Selective behavioral impairment after surgical removal of brain areas that were activated during presurgical fMRI permits us to establish a causal link between these activations and task performance. This link could not have been made on the basis of activation patterns or lesion data taken on their own. These findings support the case that some epileptic patients may represent a unique opportunity for cognitive neuroscience studies.

Adult↗

Central neural contribution to the perception of chest pain in cardiac syndrome X.

OBJECTIVE: To investigate the central neural contribution to chest pain perception in cardiac syndrome X (angina-like pain, ECG changes during stress, angiographically normal coronary arteriogram). SUBJECTS: Eight syndrome X patients and eight healthy volunteers. METHODS: Dobutamine stress using echocardiography to assess myocardial function, and positron emission tomography to measure changes in regional cerebral blood flow, as an index of neuronal activity. RESULTS: During similar doses of dobutamine, syndrome X patients and controls showed comparable regional cerebral blood flow changes in the hypothalamus, thalami, right orbito-frontal cortex, and anterior temporal poles, associated with the sensation of a fast or powerful heart beat. In patients, but not controls, the stress also generated severe chest pain associated with increased activity in the right anterior insula/frontal operculum junction. There were ischaemia-like ECG changes in the syndrome X patients, but no left ventricular dysfunction on echocardiography. Activation of the right insula during chest pain clearly distinguished the syndrome X patients from a group of patients with known coronary disease. CONCLUSIONS: Chest pain and ECG changes were not accompanied by demonstrable myocardial dysfunction in syndrome X patients, but altered central neural handling of afferent signals may contribute to the abnormal pain perception in these patients.

Aged↗

Interhemispheric transmission of visuomotor information in humans: fMRI evidence.

Normal human subjects underwent functional magnetic resonance imaging (fMRI) while performing a simple visual manual reaction-time (RT) task with lateralized brief stimuli, the so-called Poffenberger's paradigm. This paradigm was employed to measure interhemispheric transmission (IT) time by subtracting mean RT for the uncrossed hemifield-hand conditions, that is, those conditions not requiring an IT, from the crossed hemifield-hand conditions, that is, those conditions requiring an IT to relay visual information from the hemisphere of entry to the hemisphere subserving the response. The obtained difference is widely believed to reflect callosal conduction time, but so far there is no direct physiological evidence in humans. The aim of our experiment was twofold: first, to test the hypothesis that IT of visuomotor information requires the corpus callosum and to identify the cortical areas specifically activated during IT. Second, we sought to discover whether IT occurs mainly at premotor or perceptual stages of information processing. We found significant activations in a number of frontal, parietal, and temporal cortical areas and in the genu of the corpus callosum. These activations were present only in the crossed conditions and therefore were specifically related to IT. No selective activation was present in the uncrossed conditions. The location of the activated callosal and cortical areas suggests that IT occurs mainly, but not exclusively, at premotor level. These results provide clear cut evidence in favor of the hypothesis that the crossed-uncrossed difference in the Poffenberger paradigm depends on IT rather than on a differential hemispheric activation.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗