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Recent theories have hypothesized that semantic representations of action verbs and mental representations of action may be supported by partially overlapping, distributed brain networks. An fMRI experiment in healthy participants was designed to identify the common and specific regions in three different tasks from a common set of object drawings (manipulable man-made objects (MMO) and biological objects (MBO)): the generation of action words (GenA), the mental simulation of action (MSoA) and the mime of an action with the right hand (MimA). A fourth task, object naming (ON), was used as control for input/output effects. A null conjunction identified a common neural network consisting of nine regions distributed over premotor, parietal and occipital cortices. Within this common network, GenA elicited significantly more activation than either ON or MSoA in the left inferior frontal region, while MSoA elicited significantly more activation than either ON or GenA in the left superior parietal lobule. Both MSoA and GenA activated the left inferior parietal lobule more than ON. Furthermore, the left superior parietal cortex was activated to a greater extent by MMO than by MBO regardless of the tasks. These results suggest that action-denoting verbs and motor representations of the same actions activate a common frontal-parietal network. The left inferior parietal cortex and the left superior parietal cortex are likely to be involved in the retrieval of spatial-temporal features of object manipulation; the former might relate to the grasping and manipulation of any object while the latter might be linked to specific object-related gestures., (Copyright 2010 Elsevier B.V. All rights reserved.)

Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63-72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met.

Object: A naming task has been used to spare cortical areas involved in language. In the present study, a calculation task was combined with electrostimulation mapping (awake surgery) to spare cortical areas involved in calculation in patients undergoing surgery for brain lesions. The organization of language and calculation areas was analyzed in relation to these surgical data., Methods: Twenty patients with brain lesions close to areas possibly involved in calculation (dominant parietal lobe and F2) were prospectively studied over a 4-year period. Four patients had preoperative symptoms of acalculia and therefore were not included in the brain mapping procedure., Results: In 16 patients, direct electrostimulation caused calculation interferences in localized small cortical areas (< 2 cm(2)). Of the 53 calculation interferences found, 23 were independent of language areas, especially those in the inferior left parietal lobule. Various patterns of interference were observed (11 complete acalculia, 5 acalculia with wrong answers, 2 hesitations, and 5 mixed responses), although error patterns were fairly similar across angular, parietal, and frontal stimulation sites. Calculation areas in 4 patients could not be spared for oncological reasons; postoperatively, 3 of these patients showed significant acalculia symptoms. In contrast, none of the patients whose calculation areas were spared had arithmetic difficulties 1 month after surgery. Improvements in acalculia symptoms after surgery were also found in 3 of the 4 patients with preoperative calculation difficulties., Conclusions: To limit the risk of personal and professional disturbances caused by acquired anarithmetia in patients undergoing surgery for brain tumors or epilepsy, the authors think it is necessary to use a calculation task during brain mapping, especially when operating in the dominant parietal lobe.

Object: In an attempt to identify cortical areas involved in singing in addition to language areas, the authors used a singing task during direct cortical mapping in 5 patients who were amateur singers and had undergone surgery for brain tumors. The organization of the cortical areas involved in language and singing was analyzed in relation with these surgical data., Methods: One left-handed and 4 right-handed patients with brain tumors in left (2 cases) and right (3 cases) hemispheres and no significant language or singing deficits underwent surgery with the "awake surgery" technique. All patients had a special interest in singing and were involved in amateur singing activities. They were tested using naming, reading, and singing tasks., Results: Outside primary sensorimotor areas, singing interferences were rare and were exclusively localized in small cortical areas (< 1 cm(2)). A clear distinction was found between speech and singing in the Broca region. In the Broca region, no singing interference was found in areas in which interference in naming and reading tasks were detected. Conversely, a specific singing interference was found in nondominant middle frontal gyri in one patient. This interference consisted of abrupt singing arrest without apparent face, mouth, and tongue contraction. Finally, nonspecific singing interferences were found in the right and left precentral gyri in all patients (probably by interference in final articulatory mechanisms of singing)., Conclusions: Dissociations between speech and singing found outside primary sensorimotor areas showed that these 2 functions use, in some cortical stages, different cerebral pathways.

Object: It has been hypothesized that specific brain regions involved in face naming may exist in the brain. To spare these areas and to gain a better understanding of their organization, the authors studied patients who underwent surgery by using direct electrical stimulation mapping for brain tumors, and they compared an object-naming task to a famous face-naming task., Methods: Fifty-six patients with brain tumors (39 and 17 in the left and right hemispheres, respectively) and with no significant preoperative overall language deficit were prospectively studied over a 2-year period. Four patients who had a partially selective famous face anomia and 2 with prosopagnosia were not included in the final analysis., Results: Face-naming interferences were exclusively localized in small cortical areas (< 1 cm2). Among 35 patients whose dominant left hemisphere was studied, 26 face-naming specific areas (that is, sites of interference in face naming only and not in object naming) were found. These face naming-specific sites were significantly detected in 2 regions: in the left frontal areas of the superior, middle, and inferior frontal gyri (p < 0.001) and in the anterior part of the superior and middle temporal gyri (p < 0.01). Variable patterns of interference were observed (speech arrest, anomia, phonemic, or semantic paraphasia) probably related to the different stages in famous face processing. Only 4 famous face-naming interferences were found in the right hemisphere., Conclusions: Relative anatomical segregation of naming categories within language areas was detected. This study showed that famous face naming was preferentially processed in the left frontal and anterior temporal gyri. The authors think it is necessary to adapt naming tasks in neurosurgical patients to the brain region studied.

Introduction: Previous studies have shown that paroxetine, a selective serotonin reuptake inhibitor, affects brain motor pathway activity in healthy subjects using simple motor tasks. In this study, we explored the effects of paroxetine on the activity of cortical areas implicated in higher-order representations of goal-directed movements, i.e., action-related language processing., Materials and Methods: A double-blind, crossover, randomized paradigm was used to compare two 1-month treatment phases with either paroxetine (20 mg per day) or placebo. A functional magnetic resonance imaging experiment on 12 healthy subjects, conducted at the end of each treatment phase, comprised a single list of verbs and three tasks that consisted in repeating the verbs aloud, generating verbs depicting actions aloud, and mentally simulating the corresponding actions. The effects of the drug, i.e., paroxetine-placebo>0 (hyperactivation) and placebo-paroxetine >0 (hypoactivation) were assessed on the basis of the activation-rest contrast for each task., Results and Discussion: For both verb generation and mental simulation of action which both engaged higher-order representations of action, we observed hypoactivation in the left-sided prefrontal and right-sided medial premotor cortex. By contrast, we observed hyperactivation in the right-sided Brodmann's area 6 for the less demanding verb repetition task., Conclusion: Chronic treatment with paroxetine may modulate the cerebral activities elicited by action-related language tasks depending on the cognitive components involved in such tasks.

Object: To spare the cortical areas involved both in musical score reading and in language, the authors used a score reading task during direct cortical stimulation mapping in musicians undergoing operations for brain lesions. The organization of the cortical areas involved in language and score reading, respectively, was analyzed in relation with these surgical data., Methods: Seven patients with brain lesions were tested using three language tasks and a score-reading task. Preoperatively, none of them had exhibited significant language or musical ability deficits, and all had a special interest in music. All were involved in professional or amateur musical activities. Interference in score reading was found in small cortical areas, mainly in the dominant parietal lobe and sometimes in the frontal gyri. During direct stimulation, interference was either language-specific (15 sites), common to language and score-reading tasks (18 sites), or specific to the score-reading task (four sites). Different patterns of score-reading interferences (score-reading arrest, semantic paraphasia) were observed, probably corresponding to different stages of score reading. Postoperatively, some patients showed transitory score-reading difficulties related to the surgical procedure., Conclusions: The cortical areas involved in score reading can occasionally be distinct from other language areas. This could explain differential word- and score-reading impairments sometimes observed in musicians with brain lesions. Brain mapping for neurosurgical procedures in musicians should ideally be performed using a score-reading task in addition to standard language tasks, especially for mapping in the dominant parietal lobe.

Object: It has been hypothesized that a certain degree of specialization exists within language areas, depending on some specific lexical repertories or categories. To spare hypothetical category-specific cortical areas and to gain a better understanding of their organization, the authors studied patients who had undergone electrical stimulation mapping for brain tumors and they compared an object-naming task with a category-specific task (color naming)., Methods: Thirty-six patients with no significant preoperative language deficit were prospectively studied during a 2-year period. Along with a reading task, both object- and color-naming tasks were used in brain mapping. During color naming, patients were asked to identify 11 visually presented basic colors. The modality specificity of the color-naming sites found was subsequently tested by asking patients to retrieve the color attributes of objects. High individual variability was observed in language organization among patients and in the tasks performed. Significant interferences in color naming were found in traditional language regions-that is, Broca (p < 0.003) and Wernicke centers (p = 0.05)--although some color-naming areas were occasionally situated outside of these regions. Color-naming interferences were exclusively localized in small cortical areas (< 1 cm2). Anatomical segregation of the different naming categories was apparent in 10 patients; in all, 13 color-specific naming areas (that is, sites evoking no object-naming interference) were detected in the dominant-hemisphere F3 and the supramarginal, angular, and posterior parts of the temporal gyri. Nevertheless, no specific brain region was found to be consistently involved in color naming (p > 0.05). At five sites, although visually presented color-naming tasks were impaired by stimulation, auditory color naming (for example, "What color is grass?") was performed with no difficulty, showing that modality-specific areas can be found during naming., Conclusions: Within language areas, a relative specialization of cortical language areas for color naming can be found during electrical stimulation mapping.

Neuroimaging studies that look at reading processes using words, pseudowords, nonwords and letters frequently report specific left fusiform gyrus (BA37) activations. In the present study, we examined fMRI signal variations within the left and right BA37 for paired Latin letters, Korean letters and geometrical figures in discrimination and categorization tasks. Data of Pernet et al. (Pernet, C., Franceries, X., Basan, S., Cassol, E., Démonet, J.F., Celsis, P., 2004. Anatomy and time course of discrimination and categorization processes in vision: an fMRI study. NeuroImage 22, 1563-1577) were re-analyzed using a ROI methodology that highlights the selective response of the left BA37 to Latin letter categorization. First, differences according to stimulus type were observed for the categorization task only. Second, we found weaker activation for Latin letter categorization than for both geometrical figure and Korean letter categorization. Third, only Latin letter categorization elicited as left-sided activation, although the direct comparison between regions did not demonstrate a significant difference. These data suggest that the left fusiform gyrus sustains access to letter representations in memory; and results are discussed with reference to the relationship between letter categorization and word recognition and to selective vs. specific (i.e. task-independent) neural response.

Functional neuroimaging methods have reached maturity. It is now possible to start to build the foundations of a physiology of language. The remarkable number of neuroimaging studies performed so far illustrates the potential of this approach, which complements the classical knowledge accumulated on aphasia. Here we attempt to characterize the impact of the functional neuroimaging revolution on our understanding of language. Although today considered as neuroimaging techniques, we refer less to electroencephalography and magnetoencephalography studies than to positron emission tomography and functional magnetic resonance imaging studies, which deal more directly with the question of localization and functional neuroanatomy. This review is structured in three parts. 1) Because of their rapid evolution, we address technical and methodological issues to provide an overview of current procedures and sketch out future perspectives. 2) We review a set of significant results acquired in normal adults (the core of functional imaging studies) to provide an overview of language mechanisms in the "standard" brain. Single-word processing is considered in relation to input modalities (visual and auditory input), output modalities (speech and written output), and the involvement of "central" semantic processes before sentence processing and nonstandard language (illiteracy, multilingualism, and sensory deficits) are addressed. 3) We address the influence of plasticity on physiological functions in relation to its main contexts of appearance, i.e., development and brain lesions, to show how functional imaging can allow fine-grained approaches to adaptation, the fundamental property of the brain. In closing, we consider future developments for language research using functional imaging.

In order to identify the cortical areas involved in the reading process and to spare them during surgery, we systematically studied cortical areas by direct cortical stimulation in patients operated on for brain tumours. Seventy-six cortical stimulation mapping studies for language were performed in 35 monolingual and 19 bi- or multilingual patients over a 5-year period. We systematically searched for reading interference areas in addition to standard naming areas using an 'awake surgery' technique for brain mapping. A 'reading aloud' task (translated into different languages in multilingual patients) was used. Brain mapping was performed in left (44 patients) and right (10 patients) hemispheres. Cortical areas involved in reading were identified according to the type of interference, location and distinctness from naming areas. Stimulation of several major hemispheric regions resulted in significant interference with reading aloud: (i) the lower part of the pre- and postcentral gyri (P < 0.00001); (ii) the dominant supramarginal, angular and the posterior part of the superior temporal gyri (P < 0.00001); (iii) in the dominant inferior and middle frontal gyri (P < 0.001); and (iv) in the posterior part of the dominant middle temporal gyrus (P < 0.05). Interferences in reading were generally found in small cortical areas, with intervening areas evoking no reading interferences. Only partial overlap between reading and naming sites was found. Reading-specific sites were preferentially found when stimulating dominant inferior parietal or posterior temporal areas. Different types of reading interferences were noted. While 'articulatory' interferences were found in pre- and postcentral gyri bilaterally, and ocular-induced movements in bilateral middle frontal gyri, paraphasias were found mainly in the dominant supramarginal and posterior superior temporal gyri. Reading arrest sites were found in many regions. Reading interference sites were also occasionally found in the non-dominant hemisphere. In bilingual patients, if common cortical areas could be found, language- and reading-specific areas were sometimes detected, lending support to the concept that bilinguals can have relatively distinct cortical representation of their language skills. Finally, in this series, the location of reading interference sites and their relative specialization showed considerable individual variability.

To investigate the neural correlates of word learning in adults, 10 right-handed French subjects who had learned English without mastering it performed an English and a French naming task during two PET sessions, one before (PET1) and the second after (PET2) a 4-week lexical training in English. Behavioral performance was collected during the two PET exams and 2 months after (T3). At T2, performance on English naming increased in all subjects; this improvement persisted at T3, with no correlation between English performance at T2 and T3. Cerebral activation during French naming mainly showed a left frontal temporal network. The pattern specifically associated with English lexical learning included, in addition to the anterior cingulate cortex involved in attentional processing and BAs 4/6 reflecting speech output, the right cerebellum and the left insular cortex that are linked to speech gesture learning, and the right medial temporal regions, likely to reflect the involvement of episodic memory during verbal learning. Correlations between English T2/T1 performance and English T2/T1 rCBF changes reinforced the hypothesis of intervention of episodic memory since they interested right frontal, hippocampal, and lateral temporal regions. 'Predictive' correlations between English T3/T2 performance and English T2/T1 rCBF changes showed, in good reminders, increased activities in the left posterior superior temporal sulcus and middle temporal cortex probably related to efficient semantic storage of learned words.

The understanding and the prediction of the clinical outcomes of focal or degenerative cerebral lesions, as well as the assessment of rehabilitation procedures, necessitate knowing the cerebral substratum of cognitive or sensorimotor functions. This is achieved by activation studies, where subjects are asked to perform a specific task while data of their brain functioning are obtained through functional neuroimaging techniques. Such studies, as well as animal experiments, have shown that sensorimotor or cognitive functions are the offspring of the activity of large-scale networks of anatomically connected cerebral regions. However, no one-to-one correspondence between activated networks adn functions can be found. Our research aims at understanding how the activation of large-scale networks derives from cerebral information processing mechanisms, which can only explain apparently conflicting activation data. Our work falls at the crossroads of neuroimaging interpretation techniques and computational neuroscience. Since knowledge in cognitive neuroscience is permanently evolving, our research aims more precisely at defining a new modeling formalism and at building a flexible simulator, allowing a quick implementation of the models, for a better interpretation of cerebral functional images. It also aims at providing plausible models, at eht level of large-scale networks, of cerebral information processing mechanisms in humans. In this paper, we propose a formalism, based on dynamic Bayesian networks (DBNs), that respects the following constraints: an oriented, networks architecture, whose nodes (the cerebral structures) can all be different, the implementation of causality--the activation of the structure is caused by upstream nodes' activation--the explicit representation of different time scales (from 1 ms for the cerebral activity to many seconds for a PET scan image acquisition), the representation of cerebral information at the integrated level of neuronal populations, the imprecision of functional neuroimaging data, the nonlinearity and the uncertainty in cerebral mechanisms, and brain's plasticity (learning, reorganization, modulation). One of the main problems, nonlinearity, has been tackled thanks to new extensions of the Kalman filter. The capabilities of the formalism's current version are illustrated by the modeling of a phoneme categorization process, explaining the different cerebral activations in normal and dyslexic subjects.

Phonological developmental dyslexics remain impaired in phonetic categorical perception (CP) even in adulthood. We studied the brain correlates of CP in dyslexics and controls using a block design fMRI protocol and stimuli from an phonetic continuum between natural /Pa/ and /Ta/ syllables. Subjects performed a pseudo-passive listening task which does not imply voluntary categorical judgment. In the control group, categorical deviant stimuli elicited specific activations in the left angular gyrus, the right inferior frontal gyrus and the right superior cingulate cortex. These regions were not activated in the dyslexic group in which activation was observed for acoustic but not phonetic changes in stimuli. Failures to activate key regions for language perception and auditory attention in dyslexic might account for persistent deficits in phonological awareness and reading tasks. [Copyright &y& Elsevier]