A PET study of word generation in Huntington's disease: effects of lexical competition and verb/noun category.

Huntington's disease (HD) patients show language production deficits that have been conceptualized as a consequence of executive disorders, e.g. selection deficit between candidate words or switching between word categories. More recently, a deficit of word generation specific to verbs has been reported, which might relate to impaired action representations in HD. We studied the brain correlates of language impairment in HD using H(2)O(15) positron emission tomography (PET). The activation task consisted of generation of semantically appropriate nouns and verbs in dominant (low lexical selection) and selective conditions (high lexical selection). Reaction times were longer and number of errors was higher in 12 non-demented HD than in 17 age-matched controls in all conditions. In both groups, the selective condition yielded longer reaction time and a greater number of errors than the dominant one. PET data revealed that, in control subjects, the left inferior temporal gyrus was involved in the selective condition whereas it was not in HD. Moreover, activity in the anterior cingulate and the inferior frontal gyri was correlated with behavioral performance in control subjects only. In HD, the lack of implication of these regions, already shown to be crucial in lexical selection, might have been partly compensated by the activation in the left supramarginal gyrus (phonological loop activity) and the right inferior frontal gyrus (effortful retrieval processes), which might support accessory language strategies allowing patients to achieve word generation.

Object naming and action-verb generation in Parkinson's disease: a fMRI study.

INTRODUCTION: Previous studies have demonstrated that non-demented Parkinson's disease (PD) patients have particular difficulty in producing verbs in a word generation situation. Two alternative explanations for this deficit have been proposed: the "motor" theory (verbs as action representawcttions) and the "grammatical" theory (verbs as lexical category). The aim of this study was to investigate the "motor" theory by exploring the neuronal substrates of action-related word production. METHODS: Event-related functional magnetic resonance with a 3T magnetic resonance imaging (MRI) was used to explore brain activity during two overt oral language tasks, i.e., object naming (ON) and generation of action-verbs (GenA), in 14 non-demented PD patients using a common set of object drawings. The objects used were either man-made objects (MMO) or manipulable biological objects (MBO). Stimuli and tasks were randomized across subjects. Neuroimaging data were analyzed using SPM2. RESULTS: Reaction times in GenA(MBO) were significantly longer than in the other three conditions (ON(MBO), ON(MMO), GenA(MMO)). The distribution of brain activities associated with each condition resembled that reported in previous studies on healthy subjects using similar tasks; a comparison between GenA and ON revealed slight differences located above all in the premotor and prefrontal cortices, particularly as regards GeneA(MBO)>ON(MMO). Furthermore, we found positive correlations between the severity of the motor deficit (as assessed by the Unified Parkinson's Disease Rating Scale - UPDRS score) and brain activity, particularly during GenA(MBO), in the pre- and post-central gyri bilaterally, left frontal operculum, left supplementary motor area (SMA) and right superior temporal cortex. CONCLUSIONS: The direct comparison in our study of brain activity during the production of action-words and of object names did not reveal any major differences. However, our results point to a relationship between motor system dysfunction in PD and the extent of activation in verb generation, a task which implies in-depth processing of semantic representation of actions.

Paroxetine-induced modulation of cortical activity supporting language representations of action.

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.

Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy.

We conducted a randomized, double-blind, placebo-controlled, single-patient (N = 1) trial to evaluate the efficacy of zolpidem in a 48-year-old woman with an akinetic mutism. Motor and cognitive examinations and functional imaging were performed. Acute administration of zolpidem markedly improved motor performance and neuropsychological status. Cerebral metabolism ((18)F-fluorodeoxyglucose positron emission tomography) increased in postrolandic territories and in frontal cortex. Using the H(2) (15)O positron emission tomography, we found a drug-induced activation in the anterior cingulate and orbitofrontal cortices. Zolpidem induced a transient improvement in motor and cognitive performances. This paradoxical effect could result from an activation of limbic loops modulating motivational processes.

Working memory and semantic involvement in sentence processing: a case of pure progressive amnesia.

ED, a 83-year-old woman, meets the criteria of pure progressive amnesia, with gradual impairment of episodic and autobiographical memory, sparing of semantic processing and strong working memory (WM) deficit. The dissociation between disturbed WM and spared semantic processing permitted testing the role of WM in processing anaphors like pronouns or repeated names. Results showed a globally normal anaphoric behavior in two experiments requiring anaphoric processing in sentence production and comprehension. We suggest that preserved semantic processing in ED would have compensated for working memory deficit in anaphoric processing.

Subcortical aphasia: a longitudinal PET study.

BACKGROUND AND PURPOSE: Very few neuroimaging studies have focused on follow-up of subcortical aphasia. Here, overt language production tasks were used to correlate regional cerebral blood flow (rCBF) changes and language performance in patients with vascular subcortical lesions. METHODS: Seven aphasic patients were scanned twice with positron emission tomography (PET) at 1-year interval during a word-generation task. Using SPM2, Language-Rest contrast at PET1 was correlated to language performance and to time-lag from stroke. The same contrast was performed at PET2 and session effect (PET2-PET1) was correlated with performance improvement. RESULTS: At PET1, correlation between rCBF and delay from stroke involved mainly ventral regions of the left temporal cortex and mesial frontal cortex. Correlations between rCBF and performance showed predominantly left dorsal regions in the frontal, temporal, and parietal lobes, but also the left ventral temporal cortex. One year apart, language performance improved and rCBF increased in perisylvian regions bilaterally. Best performers at PET2 showed an increase of activity in left ventral temporal cortex as well as in right middle temporal gyrus. CONCLUSIONS: On follow-up, expected language improvement and increase of activation in the classical language areas and their counterparts were observed. Moreover, all correlational analyses both at PET1 and on follow-up implicated the anterior part of the left inferior temporal gyrus, suggesting a disconnection between the superior and inferior parts of the left temporal cortex and a specific role for this region in lexical semantic processing.

Renewal of the neurophysiology of language: functional neuroimaging.

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.

Functional MRI follow-up study of language processes in healthy subjects and during recovery in a case of aphasia.

BACKGROUND AND PURPOSE: The goal of this study was to develop a functional MRI (fMRI) paradigm robust and reproducible enough in healthy subjects to be adapted for a follow-up study aiming at evaluating the anatomical substratum of recovery in poststroke aphasia. METHODS: Ten right-handed subjects were studied longitudinally using fMRI (7 of them being scanned twice) and compared with a patient with conduction aphasia during the first year of stroke recovery. RESULTS: Controls exhibited reproducible activation patterns between subjects and between sessions during language tasks. In contrast, the patient exhibited dynamic changes in brain activation pattern, particularly in the phonological task, during the 2 fMRI sessions. At 1 month after stroke, language homotopic right areas were recruited, whereas large perilesional left involvement occurred later (12 months). CONCLUSIONS: We first demonstrate intersubject robustness and intrasubject reproducibility of our paradigm in 10 healthy subjects and thus its validity in a patient follow-up study over a stroke recovery time course. Indeed, results suggest a spatiotemporal poststroke brain reorganization involving both hemispheres during the recovery course, with an early implication of a new contralateral functional neural network and a later implication of an ipsilateral one.

Lexical learning of the English language: a PET study in healthy French subjects.

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.

Verb and noun generation tasks in Huntington's disease.

We compared noun- and verb-generation tasks in a demented group (n = 9, Dementia Rating Scale < or = 129) and in a non-demented group (n = 17, Dementia Rating Scale > 129) of Huntington's disease (HD) patients compared to 26 matched normal subjects. We did not find a specific deficit for verb production in non-demented patients who had a performance similar to but weaker than that of the controls across the four tasks. The profile of results was different in the demented group because, apart from a global deficit whatever the task in comparison with both non-demented and control groups, the demented patients exhibited increased difficulties in the two tasks implying verb production. The deficit of verb production observed in demented HD patients is discussed in relation to the damage to the motor loop in HD patients at later stages of disease.

Neural substrates of impaired categorical perception of phonemes in adult dyslexics: an fMRI study.

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.

Behavioral and neurofunctional changes over time in healthy and aphasic subjects: a PET Language Activation Study.

BACKGROUND AND PURPOSE: Follow-up neuroimaging studies of aphasia never addressed a comparison between aphasic and healthy subjects. Investigation of changes over time in healthy subjects during language tasks seems a prerequisite before interpretation of longitudinal changes in aphasic patients. METHODS: Six healthy subjects and 8 aphasic patients were PET scanned twice (PET1 and PET2) at a 1-year interval during a word generation task. Using SPM99, language-rest main effect was compared at PET1 and PET2 in each group, whereas group effect was assessed at each session. Correlations were analyzed in each group between performance indexes and changes in regional cerebral flood flow (rCBF) between the 2 sessions. RESULTS: Language performances were improved in both groups. rCBF decreased from PET1 to PET2 in the healthy group and increased in the aphasic group in perisylvian regions bilaterally. Correlations between performance and rCBF changes across sessions were similar in the 2 groups; positive correlations involved superior temporal cortexes bilaterally, and negative correlations concerned superior frontal and medial temporal regions. CONCLUSIONS: Increased perisylvian activation over time probably reflects improved performance at the expenses of cognitive effort in aphasic patients. Decreased activation in different neural systems suggests a familiarization effect with reduced emotional load.

Electrophysiological comparison of grammatical processing and semantic processing of single spoken nouns.

Access to meaning from speech input is a high-speed process. However, models of word comprehension stipulate that words must be analyzed at phonological, grammatical and semantic levels. Here we used event-related potentials (ERPs) to compare on-line semantic categorization (natural/manufactured) and grammatical gender categorization (masculine/feminine) of spoken monosyllabic French noun pairs. Twenty four native French speakers were instructed to spot pairs of nouns in which both stimuli pertained to a category specified prior to each block. They could make a decision either after processing the first noun (i.e., ignore the second, Release condition), or after processing both (Hold condition). Virtually identical N4 components affecting Hold and Release ERPs in relation to category expectations were elicited by the first noun in both the tasks. Their topography was intermediary between that of the N400 and that of the Left Anterior Negativity. Despite shorter Release reaction times (RTs) for gender decisions than semantic ones, Release and Hold ERPs diverged 84 ms earlier in the semantic context than in the gender context, indicating faster onset for the processing of meaning. Conversely, the offset of Hold/Release differences was observed 42 ms earlier in the gender task than in the semantic task, suggesting an earlier completion for gender categorization. In sum, electrophysiological differences induced by semantic operations commenced earlier but recovered later than those relating to grammatical gender analysis. In convergence with previous Lateralized Readiness Potential and N200 studies, our results suggest that conscious semantic access can precede access to other types of lexical information during word comprehension in highly controlled conditions.

Neural timing of visual implicit categorization.

Most of the neuroimaging studies that have shown visual category-specific activations or categorization effects have been based on a subtractive approach. In the present study, we investigated, by means of EEG, not only the net result of the categorization but also the dynamics of the process. Subjects had to perform a target detection task throughout an image set of distractors belonging to six categories: letters, geometrical figures, faces, tools, structured textures and Asiatic characters. Multivariate analyses were performed on the responses to the non-target stimuli according to their category. Categorical neural responses were only obtained on P2 latencies and N2 amplitudes. This result suggests that there are no differences in the first stage of the implicit categorization of the distractors (visual analysis and proximal stimulus representation elaboration from 100 to 220 ms) and that differences appear between 220 and 280 ms (matching to structural representations). Over-learned stimuli (e.g. letters) elicited the shortest P2 latency, contrasting with unknown categories (e.g. Asiatic characters) that revealed the longest P2 latencies and flattened N2 waves. Categorical differences indicate that the more a subject knows about an object, the less cognitive resources are used. In conclusion, our results suggest that a reduction in neural activity could reflect an improved accuracy in cognitive and cortical processing.

Demand on verbal working memory delays haemodynamic response in the inferior prefrontal cortex.

Event-related functional magnetic resonance imaging was used to test the involvement of the inferior prefrontal cortex in verbal working memory. Pairs of French nouns were presented to ten native French speakers who had to make semantic or grammatical gender decisions. Verbal working memory involvement was manipulated by making the categorization of the second noun optional. Decisions could be made after processing the first noun only (RELEASE condition) or after processing the two nouns (HOLD condition). Reaction times suggested faster processing for gender than for semantic category in RELEASE. Despite the absence of anatomical difference across tasks and conditions in the wide activated network, the haemodynamic response peak latencies of the inferior prefrontal cortex were significantly delayed in HOLD versus RELEASE while no such peak delay was observed in the superior temporal gyrus. Interestingly, this pattern did not interact with language tasks. This study shows that cognitive manipulation can influence haemodynamic time-course and suggests that the main cognitive process determining inferior prefrontal activation is verbal working memory rather than specific linguistic processes such as grammatical or semantic analysis.

Deficit of verb generation in nondemented patients with Parkinson's disease.

Clinical and neuroimaging studies have shown that verb processing suggests a preferential participation of a prefrontal network, which is dysfunctional in Parkinson's disease (PD). To assess a verb processing deficit in PD, we compared noun- and verb-generation tasks for 34 nondemented PD patients (according to the Dementia Rating Scale) with 34 matched normal subjects, using two intracategory tasks (noun/noun and verb/verb generation) and two intercategory tasks (noun/verb and verb/noun generation). PD patients were significantly impaired in the two tasks involving verb production, i.e., verb/verb and noun/verb generation, whereas their performance was similar to those of controls in the two tasks requiring noun production. For the two impaired tasks, we assessed 1) the influence of lexical competition that corresponds to the presence of several candidate words for a given stimulus; 2) the influence of slight cognitive dysfunction; and 3) the influence of motor deficit. Significant correlations were found between DRS scores and performance on the noun/verb task, and no significant correlations were found between lexical competition or motor deficit and performance. The specific deficit for verb production in PD patients is discussed in relation to deficits affecting either action or grammatical representations.

Enhanced response of the left frontal cortex to slowed down speech in dyslexia: an fMRI study.

Language difficulties of dyslexic subjects may result partly from a basic deficit in processing rapidly changing sensory inputs. In this fMRI study, we compared brain activities in adult dyslexics and controls during implicit categorical perception of phonemes with normal and slowed down stimuli. Perception of phonemic contrasts activated a frontal parietal network (Broca's area and the left supramarginal gyrus) in which the frontal component was down-regulated by slowed speech in controls and enhanced in dyslexic subjects. No modulation by speech rate was observed in the left supra-marginal gyrus. Enhancement of activity in Broca's area for slowed speech in dyslexic subjects might represent a neural basis of the improvement of performance that has been observed after remediation using this type of stimuli.

Seeing, since childhood, without ventral stream: a behavioural study.

We report the case of a 30-year-old man (S.B.) who developed visual agnosia following a meningoencephalitis at the age of 3 years. MRI disclosed extensive bilateral lesions of the occipital temporal visual pathway (ventral stream) and lesions in the right dorsal pathway, sparing primary visual cortices. S.B. showed a severe visual recognition deficit (texture, colour, objects, faces and words), although movement and space perception were largely preserved. His remaining visual capacities illustrate the competence of an isolated dorsal system which essentially functions on the sole basis of magnocellular afferents (low spatial resolution, high sensitivity to low contrast and moving stimuli). Patient S.B. also shows remarkable visuomotor competences, despite his perceptual limitations. It is suggested that his perceptual capacities correspond to the visual processing limitations of the dorsal visual stream, which in this patient have become accessible to perceptual awareness.

Resolução anafórica e foco do discurso: o caso do pronome demonstrativo francês híbrido Este (celui-ci) / Anaphoric resolution and discourse focus: the case of the french hybrid demonstrative pronoun (celui-ci)

Na tradição da teoria da centralização, muitos estudos mostraram uma sensibilidade significativa dos pronomes anafóricos para se referir às entidades focalizadas na representação do discurso. Essa sensibilidade estaria ausente nas expressões explícitas e nos substantivos repetidos. De acordo com os princípios dessa teoria, apresentamos um experimento com o objetivo de estudar a função referencial de identificação de uma expressão híbrida, o pronome demonstrativo este. Os resultados indicam que a utilização dessa expressão está fortemente restringida pelas entidades de focalização e estaria motivada a estabelecer o centro de atenção sobre uma entidade mediamente focalizada. Esses resultados são discutidos à luz da teoria da centralização(AU)