Dipartimento di Psicologia

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.

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.

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.

significantly lower rCBF in Sz relative to the controls (Z threshold = 2,80; corrected p =0.05; region size= 360 (k) voxels, P(l1max>k)=0.015), presumed to represent diminished tertiary olfactory processing. Importantly, controls (but not Sz), had significantly increas~d rCB~in ,olf~ctory activation than in baseline task condition. This activation 10 only controls, was shown in Talairach Atlas to include Rt hippocampus, Rt medial temporal/lateral, Left occi~i~" and left .me~al te',llporallobe. By region of interest ana~ysls It included inf~~or/nuddle temporal gyrus, fusiform and lingual gyrus o~occ~plto-te~poral, I~be, posterior parahippocampal gy~s, and~e~or medial occl~ltal. This study data identified deficient activation of the (tertiary) cortical and medial temporal lobe (secondary) structures involved in olfactory processing. Data suggests that the abnor-:nality underlying deficient olfactory discrimination in patients may originate from MTL lobe abn?rmalities.

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([123I]β-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]β-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]β-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.

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.

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 Abbreviations: BA ϭ Brodmann area; CVS ϭ caloric vestibular stimulation; NV ϭ neck muscle mechanical vibration; PIVC ϭ parietoinsular vestibular cortex; rCBF ϭ regional cerebral blood flow; Ri ϭ retroinsular

We assessed the effects of age of acquisition and language exposure on the cerebral correlates of lexical retrieval in high-proficient, early-acquisition bilinguals. Functional MRI was used to study Spanish–Catalan bilinguals who acquired either Spanish or Catalan as a first language in the first years of life. Subjects were exposed to the second language at 3 years of age, and have used both languages in daily life since then. Subjects had a comparable level of proficiency in the comprehension of both languages. Lexical retrieval with the verbal fluency task resulted in the well-established pattern of left hemispheric activation centered on the inferior frontal region. The effect of age of acquisition was assessed by dividing the subjects into two groups, on the basis of the language acquired first (Catalan-born or Spanish-born bilinguals). Functional comparisons indicated that less extensive brain activation was associated with lexical retrieval in the language acquired earlier in life. The two groups were also different in language usage/exposure, as assessed with a specific questionnaire; in particular, the exposure to the second language (Spanish) was less intensive in the case of Catalans. This was reflected in a significant interaction, indicating a more extensive activation in Catalans during production in Spanish. Overall, these results indicate that, during a production task, both age of acquisition and language exposure affect the pattern of brain activation in bilinguals, even if both languages are acquired early and with a comparable level of proficiency. Hum. Brain Mapping 19:170–182, 2003. © 2003 Wiley-Liss, Inc.

rCBF PET scans were used to study the physiological bases of lip-reading, 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 (non-lexical lip-reading) was associated with bilateral activation of 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 phonogical processing, speech and mouth motor planning and execution. In addition, non-lexical lip-reading also differentially activated visual motion areas. Lexical access through lip-reading 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 lip-reading further clarified the role of these areas in gaining access to language through lipreading. The results suggest cortical activation circuits for lip-reading from action representations which may differentiate lexical access from nonlexical processes.

The [ 18 F]fluorodeoxyglucose ([ 18 F]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) [ 18 F]FDG PET data. We show that a 10-min noninteractive voxelbased 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.

A 2-["F]-Fluoro-2-Deoxy-v-Glucose ([ 1°F]FDG) and positron emission tomography (PETI study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion . In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated . At follow-up evaluation the patient showed an almost complete recovery from unilateral neglect . This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired . Another patient with an extensive right cerebral i .schaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase . A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found . These data suggest that the remission of unilateral neglect might he associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere.

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 . 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.

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 .

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.

In a small proportion of the normal population, stimulation in one modality can lead to perceptual experience in another, a phenomenon known as synaesthesia. In the most common form of synaesthesia, hearing a word can result in the experience of colour. We have used the technique of PET, which detects brain activity as changes of regional cerebral blood flow (rCBF), to study the physiology of colour-word synaesthesia in a group of six synaesthete women. During rCBF measurements synaesthetes and six controls were blindfolded and were presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synaesthesia in synaesthetes. In both groups word stimulation compared with tone stimulation activated the classical language areas of the perisylvian regions. In synaesthetes, a number of additional visual associative areas, including the posterior inferior temporal cortex and the parieto-occipital junctions, were activated. The former has been implicated in the integration of colour with shape and in verbal tasks which require attention to visual features of objects to which words refer. Synaesthetes also showed activations in the right prefrontal cortex, insula and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas VI, V2 and V4. These results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration. In the case of colour-word synaesthesia, conscious visual experience appears to occur without activation of the primary visual cortex.