Ferruccio Fazio

Listening to Action-related Sentences Activates Fronto-parietal Motor Circuits

Observing actions made by others activates the cortical circuits responsible for the planning and execution of those same actions. This observationexecution matching system (mirror-neuron system) is thought to play an important role in the understanding of actions made by others. In an fMRI experiment, we tested whether this system also becomes active during the processing of action-related sentences. Participants listened to sentences describing actions performed with the mouth, the hand, or the leg. Abstract sentences of comparable syntactic structure were used as control stimuli. The results showed that listening to action-related sentences activates a left fronto-parieto-temporal network that includes the pars opercularis of the inferior frontal gyrus (Brocas area), those sectors of the premotor cortex where the actions described are motorically coded, as well as the inferior parietal lobule, the intraparietal sulcus, and the posterior middle temporal gyrus. These data provide the first direct evidence that listening to sentences that describe actions engages the visuomotor circuits which subserve action execution and observation.

Localization of grasp representations in humans by PET: 1. Observation versus execution

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 (Brodmanns area 21) and the caudal part of the left inferior frontal gyrus (Brodmanns area 45). The possible functional homologies between these areas and the monkey STS region and frontal area F5 are discussed.

Discrimination between Alzheimer Dementia and Controls by Automated Analysis of Multicenter FDG PET

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimers disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.

Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results

BACKGROUND Low-dose spiral CT of the chest effectively detects early-stage lung cancer in high-risk individuals. The high rate of benign nodules and issues of making a differential diagnosis are critical factors that currently hamper introduction of large-scale screening programmes. We investigated the efficacy of repeated yearly spiral CT and selective use of positron emission tomography (PET) in a large cohort of high-risk volunteers. METHODS We enrolled 1035 individuals aged 50 years or older who had smoked for 20 pack-years or more. All patients underwent annual low-dose CT, with or without PET, for 5 years. Lesions up to 5 mm were deemed non-suspicious and low-dose CT was repeated after 12 months (year 2). FINDINGS By year 2, 22 cases of lung cancer had been diagnosed (11 at baseline, 11 at year 2). 440 lung lesions were identified in 298 (29%) participants, and 95 were recalled for high-resolution contrast CT. PET scans were positive in 18 of 20 of the identified cancer cases. Six patients underwent surgical biopsy for benign disease because of false-positive results (6% of recalls, 22% of invasive procedures). Complete resection was achieved in 21 (95%) lung cancers, 17 (77%) were pathological stage I (100% at year 2), and the mean tumour size was 18 mm. There were no interval lung cancers in the 2.5 years of follow-up (average time on study from randomisation to last contact), although 19 individuals were diagnosed with another form of cancer (two deaths and 17 non-fatal admissions). INTERPRETATION Combined use of low-dose spiral CT and selective PET effectively detects early lung cancer. Lesions up to 5 mm can be checked again at 12 months without major risks of progression.

Brain processing of native and foreign languages.

We used positron emission tomography to study brain activity in adults while they were listening to stories in their native language, in a second language acquired after the age of seven, and in a third unknown language. Several areas, similar to those previously observed in monolinguals, were activated by the native but not by the second language. Both the second and the unknown language yielded distinct left-hemispheric activations in areas specialized for phonological processing, which were not engaged by a backward speech control task. These results indicate that some brain areas are shaped by early exposure to the maternal language, and are not necessarily activated by the processing of a second language to which they have been exposed for a limited time later in life.

Syntax and the Brain: Disentangling Grammar by Selective Anomalies

Many paradigms employed so far with functional imaging in language studies do not allow a clear differentiation of the semantic, morphological, and syntactic components, as traditionally defined within linguistic theory. In fact, many studies simply consider the brains response to lists of unrelated words, rather than to syntactic structures, or do not neutralize the confounding effect of the semantic component. In the present PET experiment, we isolated the functional correlates of morphological and syntactic processing. The neutralization of the access to the lexical-semantic component was achieved by requiring the detection of anomalies in written sentences consisting of pseudowords. In both syntactic and morphosyntactic processing, the involvement of a selective deep component of Brocas area and of a right inferior frontal region was detected. In addition, within this system, the left caudate nucleus and insula were activated only during syntactic processing, indicating their role in syntactic computation. These findings provide original in vivo evidence that these brain structures, whose individual contribution has been highlighted by clinical studies, constitute a neural network selectively engaged in morphological and syntactic computation.

Different neural systems for the recognition of animals and man-made tools

Using positron emission tomography, we mapped brain activity in normal volunteers during the recognition of visual stimuli representing living (animals) and nonliving (artefacts) entities. The subjects had to decide whether pairs of visual stimuli were different representations of the same object, or different objects. Animal recognition was associated with activations in the inferior temporo-occipital areas, bilaterally, whereas artefact recognition engaged a predominantly left hemispheric network, involving the left dorsolateral frontal cortex. These findings, which concur with clinical observations in neurological patients, provide in vivo evidence for a fractionation of the neural substrates of semantic knowledge in man.

The role of age of acquisition and language usage in early, high‐proficient bilinguals: An fMRI study during verbal fluency

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.

Different brain correlates for watching real and virtual hand actions.

We investigated whether observation of actions reproduced in three-dimensional virtual reality would engage perceptual and visuomotor brain processes different from those induced by the observation of real hand actions. Participants were asked to passively observe grasping actions of geometrical objects made by a real hand or by hand reconstructions of different quality in 3D virtual reality as well as on a 2D TV screen. We found that only real actions in natural environment activated a visuospatial network including the right posterior parietal cortex. Observation of virtual-reality hand actions engaged prevalent visual perceptual processes within lateral and mesial occipital regions. Thus, only perception of actions in reality maps onto existing action representations, whereas virtual-reality conditions do not access the full motor knowledge available to the central nervous system.

Word and picture matching: A PET study of semantic category effects

We report two positron emission tomography (PET) studies of cerebral activation during picture and word matching tasks, in which we compared directly the processing of stimuli belonging to different semantic categories (animate and inanimate) in the visual (pictures) and verbal (words) modality. In the first experiment, brain activation was measured in eleven healthy adults during a same/different matching task for textures, meaningless shapes and pictures of animals and artefacts (tools). Activations for meaningless shapes when compared to visual texture discrimination were localized in the left occipital and inferior temporal cortex. Animal picture identification, either in the comparison with meaningless shapes and in the direct comparison with non-living pictures, involved primarily activation of occipital regions, namely the lingual gyrus bilaterally and the left fusiform gyrus. For artefact picture identification, in the same comparison with meaningless shape-baseline and in the direct comparison with living pictures, all activations were left hemispheric, through the dorsolateral frontal (Ba 44/6 and 45) and temporal (Ba 21, 20) cortex. In the second experiment, brain activation was measured in eight healthy adults during a same/different matching task for visually presented words referring to animals and manipulable objects (tools); the baseline was a pseudoword discrimination task. When compared with the tool condition, the animal condition activated posterior left hemispheric areas, namely the fusiform (Ba 37) and the inferior occipital gyrus (Ba 18). The right superior parietal lobule (Ba 7) and the left thalamus were also activated. The reverse comparison (tools vs animals) showed left hemispheric activations in the middle temporal gyrus (Ba 21) and precuneus (Ba 7), as well as bilateral activation in the occipital regions. These results are compatible with different brain networks subserving the identification of living and non-living entities; in particular, they indicate a crucial role of the left fusiform gyrus in the processing of animate entities and of the left middle temporal gyrus for tools, both from words and pictures. The activation of other areas, such as the dorsolateral frontal cortex, appears to be specific for the semantic access of tools only from pictures.