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Vocabulary acquisition is such a major aspect of language learning in children, but also in adults when learning a foreign language, that a dedicated vocabulary learning device may exist within the language organ. To identify the relevant brain systems, we performed regional cerebral blood flow measurements in normal subjects while they were learning a list of neologisms or a list of word–nonword pairs. Structures implicated in phonological short-term memory (Broca's area, left temporo-parietal junction) were steadily activated during nonwords learning, while the left temporal lobe neocortical and paralimbic structures (parahippocampal region), associated with long-term memory, contributed to learning in a time-dependent manner, with maximal activation at the beginning of the process. The neural system specifically activated when learning new vocabulary was strongly lateralized to the left hemisphere. This evidence refines current models of memory function and supports theories which emphasise the importance of phonological competence in hemispheric dominance for language.

A new head holder for the fixation and repositioning of the patient head in PET, CT, and MR scanners has been designed and tested. With this device, a bidimensional correlation between functional and anatomical brain images can also be obtained. Head fixation and repositioning are achieved using the patient's dental morphology as an anatomical reference. With a dentistic material, a mold of the patient's teeth is obtained in a few minutes. The molding substance rests on a plastic support, fixed to the head holder. Each time the patient undergoes a new study, his/her personal mold is used, ensuring accurate head repositioning. External markers fixed on the head holder (made visible in lateral PET and CT projection images, midsaggital MR images, and also on the axial images) make it possible to record and recognize the angular orientation and the position of the brain in the three-dimensional space, to correlate images of the same patient obtained with different neuroimaging modalities, and to accurately reposition patients for follow-up studies. The head holder was tested on several subjects. Fixation and repositioning accuracy of within 2.5 mm were achieved in the three-dimensional space. Orientation accuracy was 1 degree.

The wide variety of techniques and tasks used to study the neural correlates of noun and verb processing has resulted in a body of inconsistent evidence. We performed a functional magnetic resonance imaging (fMRI) experiment to detect grammatical class effects that generalize across tasks. A total of 12 participants undertook a grammatical-class switching task (GCST), in which they were presented with a noun (or a verb) and were asked to retrieve the corresponding verb (or noun), and a classical picture naming task (PNT) widely used in the previous aphasiological and imaging literature. The GCST was explicitly designed to ensure control over confounding variables, such as stimulus complexity or imageability. Conjunction analyses of the haemodynamic responses measured in the two tasks indicated a shared verb-related activation of a dorsal premotor and posterior parietal network, pointing to a strong relationship between verb representation and action-oriented (visuo-)spatial knowledge. On the other hand, no brain area was consistently associated with nouns in both tasks. Moreover, there were task-dependent differences between noun and verb retrieval both at behavioural and at physiological level; the grammatical class that elicited the longest reaction times in both tasks (i.e., verbs in the PNT and nouns in the GCST) triggered a greater activation of the left inferior frontal gyrus. Therefore, we suggest that this area reflects a general increase in task demand rather than verb processing per se.

Introduction Current data on the neural correlates of noun and verb processing are inconsistent as studies using different imaging techniques and/or different tasks have provided remarkably different results. This fMRIstudy was designed to clarify this issue by assessing task-independent and task-dependent grammatical-class-specific effects during lexical retrieval tasks. Materials and Methods - Subjects: 12 right-handed Italian students (F=6, M=6), aged 20-34, 15 years of schooling. Materials: subjects retrieved nouns and verbs during two different tasks: a picture naming task similar to the one adopted in previous experiments (PNT) and a retrieval task (NVRT ) were verbs or nouns were derived from the corresponding noun or verb (say “vincere” (to win) when reading “vittoria” (victory), or vicversa; NVRT, see Crepaldi et al., 2006). It should be noted that the typical picture naming task used to assess noun or verb retrieval is necessarily imbalanced for imageability and visual complexity, with pictures for verbs being more complex than pictures for objects. On the other hand, in NVRT task nouns and verbs had the same level of imageability. We also had a simple reading task for nouns or for verbs as a control experiment. Before fMRI scans, subject familiarized with the experimental stimuli so that strategic search of targets was minimized. Here we recorded VOTs for the different tasks. - fMRI data acquisition and analysis: 1.5 T Marconi-Philips Infinion Scanner, EPI gradient echo sequence TR: 3”; TE: 60 msec; Flip angle: 90°. Data were collected in alternating 30” blocks of baseline and experimental tasks. Condition-specific effects were estimated according to the general linear model (GLM) in SPM2. Statistical thresholds: p

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.

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.

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.

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.

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.

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.

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.

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). (H2O)-O-15 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

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.

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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.

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.

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

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.

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.

As discussed by ourselves[1xRight on in sign language. Paulesu, E. and Mehler, J. Nature. 1998; 392: 233–234Crossref | PubMed | Scopus (17)See all References][1]and also by Hickok and colleagues in the preceding comment[2xWhat's right about the neural organization of sign language? A perspective on recent neuroimaging results. Hickok, G., Bellugi, U., and Klima, E. Trends Cognit. Sci. 1998; 2: 465–468Abstract | Full Text | Full Text PDF | PubMed | Scopus (33)See all References][2]and elsewhere[3xLanguage, modality and the brain. Bellugi, U., Poizner, H., and Klima, E. Trends Neurosci. 1989; 12: 380–388Abstract | Full Text PDF | PubMed | Scopus (79)See all References][3], we believe that the available evidence from fMRI and other studies points to a left hemispheric dominance for language, even in the case of sign language[4xThe neurobiology of sign language and its implications for the neural basis of language. Hickok, G., Bellugi, U., and Klima, E. Nature. 1996; 381: 699–702Crossref | PubMed | Scopus (97)See all References, 5xNeural correlates of thinking in sign language. McGuire, P. et al. NeuroReport. 1997; 8: 695–698Crossref | PubMedSee all References, 6xSign language aphasia during left-hemisphere Amytal injection. Damasio, A. et al. Nature. 1986; 322: 363–365Crossref | PubMed | Scopus (35)See all References]. However, while the left hemispheric activations seen in recent imaging data for sign language could be largely predicted from lesion data, we are still inclined to believe, in contrast to Hickok et al.[2xWhat's right about the neural organization of sign language? A perspective on recent neuroimaging results. Hickok, G., Bellugi, U., and Klima, E. Trends Cognit. Sci. 1998; 2: 465–468Abstract | Full Text | Full Text PDF | PubMed | Scopus (33)See all References][2], that the right hemispheric activations described by Neville et al.[7xCerebral organization for language in deaf and hearing subjects: biological constraints and effects of experience. Neville, H. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 922–929Crossref | PubMed | Scopus (302)See all References][7]are not artefactual—even though a real surprise, given the expectation from patient data. The baseline for the sign-language comprehension task used by Neville et al. (observation of non-linguistic gestures made by a signer) was closely matched to the experimental task. Auditory-language comprehension tasks using a similarly close baseline, such as backwards speech, do not show such prominent activations in the right hemisphere[8xThe bilingual brain: proficiency and age of acquisition of the second language. Perani, D. et al. Brain. 1998; 121: 1841–1852Crossref | PubMed | Scopus (370)See all References][8].As we proposed in our commentary[1xRight on in sign language. Paulesu, E. and Mehler, J. Nature. 1998; 392: 233–234Crossref | PubMed | Scopus (17)See all References][1], reconciliation of the mismatch between functional imaging and lesion data will require further investigations on both sides. Even if our suggestion[1xRight on in sign language. Paulesu, E. and Mehler, J. Nature. 1998; 392: 233–234Crossref | PubMed | Scopus (17)See all References][1]turned out to be true—that the right hemispheric activations seen for sign language by Neville et al. could have been due to prosodic processing[9xDominant language functions of the right hemisphere? Prosody and emotional gesturing. Ross, E. and Mesulam, M. Arch. Neurol. 1979; 36: 144–148Crossref | PubMed | Scopus (381)See all References][9]—this would still be a challenge for our understanding of the biological causes of the regional brain distribution of linguistic competences in both hearing and congenitally deaf subjects. Left-sided `dominance', together with right-sided linguistic competence of the kind seen in hearing subjects[9xDominant language functions of the right hemisphere? Prosody and emotional gesturing. Ross, E. and Mesulam, M. Arch. Neurol. 1979; 36: 144–148Crossref | PubMed | Scopus (381)See all References, 10xThe role of the right hemisphere in the interpretation of figurative aspects of language: a positron emission tomography activation study. Bottini, G. et al. Brain. 1994; 117: 1231–1253Crossref | PubMed | Scopus (407)See all References], is a complex scenario that is not evaluated by the hypotheses usually discussed in neuro-linguistics and neither is it discussed by Hickok et al. in their present comment.

It is generally believed that the Earth's magnetic field arises from dynamo action in the convecting outer core1-3. Thus the geomagnetic field, and especially its strength, can provide information about core processes. Recent determinations of the geomagnetic palaeointensity using Archaean and early Proterozoic samples from the Kaapvaal and Superior cratons are consistent with a sharp increase in the magnitude of the geomagnetic field between 2.7 and 2.1 Gyr. Analysis of published late Archaean and early Proterozoic apparent polar wander paths shows that an abrupt change in the rate and style of continental motion occurred at about 2.5-2.6 Gyr ago. If this change is also interpreted to be related to the growth of an inner core, then, an intriguing conjecture arises that the Archaean-Proterozoic transition is related to inner core nucleation. © 1987 Nature Publishing Group.

The ligand PK11195 is selective for the peripheral benzodiazepine binding site and exhibits minimal binding in normal brain. In brain lesions, however, there is a massive increase in binding, which in vitro studies have demonstrated is associated with infiltrating macrophages and activated microglia. Here, the binding of [11C]PK11195 was studied in the brains of multiple sclerosis patients using a CTI/Siemens 953B positron emission tomograph with retractable septa, acquiring data in either two-dimensional (2D) or 3D mode. Images acquired in 2D following injection of ~ 370 MBq were generally featureless. In some cases, poorly circumscribed signals were observed in brain stem or thalamus but with a minimal signal-to-noise ratio. However, regions showing gadolinium enhancement in magnetic resonance (MR) imaging, indicating a blood-brain barrier disturbance and known from histology to contain macrophages, never showed an elevated [11C]PK11195 signal. Three dimensional positron emission tomography (PET), using similar doses of radioligand, gave a fivefold increase in counts and produced a marked improvement in image quality. Gadolinium-enhancing lesions were clearly visualized, together with hot spots of binding in regions with apparently normal MR imaging appearance. The PET signals were often well delineated and, following coregistration with MR images, could be localized to well-defined anatomical structures such as individual thalamic nuclei and white matter tracts. In several cases, these structures identified pathways correlating with the clinical condition of the patient. It was concluded that while 2D PET and [11C]PK11195 can be used to image gross macrophage infiltration in the central nervous system, more subtle pathology requires 3D scanning in order to realize the full potential of the methodology.

International audience; 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.

Summary A rhyming and a short-term memory task with visually presented letters were used to study brain activity in five compensated adult developmental dyslexics. Their only cognitive difficulty was in phonological processing, manifest in a wide range of tasks including spoonerisms, phonemic fluency and digit naming speed. PET scans showed that for the dyslexics, a subset only of the brain regions normally involved in phonological processing was activated: Broca 's area during the rhyming task, temporo-parietal cortex during the short-term memory task. In contrast to normal controls these areas were not activated in concert. Furthermore the left insula was never activated. We propose that the defective phonological system of these dyslexics is due to weak connectivity between anterior and posterior language areas. This could be due to a dysfunctional left insula which may normally act as an anatomical bridge between Broca's area, superior temporal and inferior parietal cortex. The independent activation of the posterior and anterior speech areas in dyslexics supports the notion that representations of unsegmented and segmented phonology are functionally and anatomically separate.

Positron emission tomography (PET) was used to localize brain regions that are active during the observation of grasping movements. Normal, right-handed subjects were tested under three conditions. In the first, they observed grasping movements of common objects performed by the experimenter. In the second, they reached and grasped the same objects. These two conditions were compared with a third condition consisting of object observation. On the basis of monkey data, it was hypothesized that during grasping observation, activations should be present in the region of the superior temporal sulcus (STS) and in inferior area 6. The findings in humans demonstrated that grasp observation significantly activates the cortex of the middle temporal gyrus including that of the adjacent superior temporal sulcus (Brodmann's area 21) and the caudal part of the left inferior frontal gyrus (Brodmann's area 45). The possible functional homologies between these areas and the monkey STS region and frontal area F5 are discussed.

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

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.

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.

Scopolamine, a muscarinic antagonist, impairs memory performance in both humans and animals. In this study, repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers whilst performing auditory verbal memory tasks, before and after the administration of scopolamine (0.4 mg s.c.) or placebo. Compared to placebo, scopolamine increased blood flow in the lateral occipital cortex bilaterally and the left orbitofrontal region. Scopolamine decreased rCBF in the region of the right thalamus, the precuneus and the right and left lateral premotor areas. Scopolamine attenuated memory-task-induced increases of rCBF in the left and right prefrontal cortex and the right anterior cingulate region. These data suggest that acute blockade of cholinergic neurotransmission affects diverse brain areas, including components of the visual and motor systems, and, in addition, modulates memory task activations at distinct points in a distributed network for memory function.

We investigated cerebral activity in six normal volunteers using PET to explore the hypothesis that the right hemisphere has a specific role in the interpretation of figurative aspects of language such as metaphors. We also mapped the anatomical structures involved in sentence comprehension. During regional cerebral blood flow measurement subjects were asked to perform three different linguistic tasks: (i) metaphorical comprehension; (ii) literal comprehension of sentences; and (iii) a lexical-decision task. We found that comprehension of sentences compared with the lexical-decision task, induced extensive activation in several regions of the left hemisphere, including the prefrontal and basal frontal cortex, the middle and inferior temporal gyri and temporal pole, the parietal cortex and the precuneus. Comprehension of metaphors was associated with similar activations in the left hemisphere, but in addition, a number of sites were activated in the right hemisphere: the prefrontal cortex, the middle temporal gyrus, the precuneus and the posterior cingulate. We conclude that the interpretation of language involves widespread distributed systems bilaterally with the right hemisphere having a special role in the appreciation of metaphors.

The cerebral representation of space depends on the integration of many different sensory inputs. The vestibular system provides one such input and its dysfunction can cause profound spatial disorientation. Using positron emission tomography (PET), we measured regional cerebral perfusion with various vestibular stimulations to map central vestibular projections and to investigate the cerebral basis of spatial disorientation. We showed that the temporoparietal cortex, the insula, the putamen, and the anterior cingulate cortex are the cerebral projections of the vestibular system in man and that the spatial disorientation caused by unilateral vestibular stimulation is associated with their asymmetric activation.

BY repeating words 'in our head', verbal material (such as telephone numbers) can be kept in working memory1 almost indefinitely. This 'articulatory loop' includes a subvocal rehearsal system2-6 and a phonological store3,6-10. Little is known about neural correlates of this model of verbal short-term memory. We therefore measured regional cerebral blood flow, an index of neuronal activity, in volunteers performing a task engaging both components of the articulatory loop (short-term memory for letters) 5-10 and a task which engages only the subvocal rehearsal system (rhyming judgement for letters) 4,11. Stimuli were presented visually and the subjects did not speak. We report here that comparisons of distribution of cerebral blood flow in these conditions localized the phonological store to the left supramarginal gyrus whereas the subvocal rehearsal system was associated with Broca's area. This is, to our knowledge, the first demonstration of the normal anatomy of the components of the 'articulatory loop'. © 1993 Nature Publishing Group.

Corpus callosum (CC) atrophy by magnetic resonance imaging (MRI) is a common finding in multiple sclerosis (MS). In order to examine the relationship between CC atrophy and cortical brain metabolism, we compared the cerebral metabolic rates for glucose (CMRglc), measured by positron emission tomography (PET), of 8 MS patients with evidence of CC atrophy on midsagittal MRI, 8 MS patients without CC atrophy and 10 healthy controls. Results showed no significant differences in supratentorial CMRglc absolute values between the three groups, although a slight metabolic reduction was observed in both MS groups compared with normal controls. By contrast, only patients with CC atrophy showed greater directional metabolic asymmetry than normals, the left frontal, temporal and parietal association cortices being significantly lower than the right. Predominant left hemispheric metabolic reductions were not accompanied by a corresponding left-sided predominance in the extent of MRI-detected demyelinating lesions. Therefore our data suggest that CC atrophy interfers more with left than with right metabolic function.

Psychopharmacological activation, in conjunction with positron emission tomographic measurements of regional cerebral blood flow (rCBF), was used to investigate the neurotransmitter basis of a specific cognitive function in man. Monoaminergic neurotransmission was pharmacologically manipulated during performance of auditory - verbal memory tasks. Statistical parametric mapping was used to identify the brain sites of interaction between memory-induced increases in rCBF and active drugs. Memory task-induced increases in rCBF in the left prefrontal cortex were attenuated by apomorphine, a non-selective dopamine agonist, whilst buspirone, a serotonin1A partial agonist, augmented rCBF increases in this area. In addition, apomorphine and buspirone augmented memory-induced increases in rCBF centred in the posterior cingulate cortex, whilst buspirone alone attenuated rCBF increases in the retrosplenial cortex and posterior parahippocampal gyrus. These regionally selective interactions may represent neuromodulatory effects of monoaminergic neurotransmission on a specific cognitive function in man.

Human amnesia is a clinical syndrome exhibiting the failure to recall past events and to learn new information. Its “pure” form, characterized by a selective impairment of long-term memory without any disorder of general intelligence or other cognitive functions, has been associated with lesions localized within Papez's circuit and some connected areas. Thus, amnesia could be due to a functional disconnection between components of this or other neural structures involved in long-term learning and retention. To test this hypothesis, we measured regional cerebral metabolism with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) and positron emission tomography (PET) in 11 patients with “pure” amnesia. A significant bilateral reduction in metabolism in a number of interconnected cerebral regions (hippocampal formation, thalamus, cingulate gyrus, and frontal basal cortex) was found in the amnesic patients in comparison with normal controls. The metabolic impairment did not correspond to alterations in structural anatomy as assessed by magnetic resonance imaging (MRI). These results are the first in vivo evidence for the role of a functional network as a basis of human memory.

In two separate experiments positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while normal subjects performed the Stroop colour word interference test, a test of selective attention. In the first experiment performance of the Stroop task was associated with activation of right orbito-frontal and bilateral parietal structures, an unexpected result in view of previously reported findings. In addition, there were highly significant time related focal changes in rCBF. A second experiment was therefore carried out which altered the experimental parameters to replicate an earlier study. In this second experiment focal activation of the right anterior cingulate and right frontal polar cortex occurred during the Stroop task. As in the first experiment significant time effects were again apparent. To determine the functionally related brain systems during the performance of the Stroop task a correlation analysis was carried out in relation to blood flow changes induced by experimental manipulation in the right anterior cingulate. This analysis indicated the engagement of a widespread network of anterior brain regions and reciprocal inhibition of posterior brain regions during the performance of the task. The results provide evidence for the involvement of anterior right hemisphere and medial frontal structures in attentional tasks but also indicate that time effects can confound task specific activations. Furthermore subtle experimental treatment parameters, such as stimulus presentation rate, influence the degree and distribution of observed activations.

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.