Effect of levodopa on both verbal and motor representations of action in Parkinson's disease: a fMRI study.

Previous studies have demonstrated that non-demented Parkinson's disease (PD) patients have a specific impairment of verb production compared with noun generation. One interpretation of this deficit suggested the influence of striato-frontal dysfunction on action-related verb processing. The aim of our study was to investigate cerebral changes after motor improvement due to dopaminergic medication on the neural circuitry supporting action representation in the brain as mediated by verb generation and motor imagery in PD patients. Functional magnetic resonance imaging on 8 PD patients in "ON" dopaminergic treatment state (DTS) and in "OFF" DTS was used to explore the brain activity during three different tasks: Object Naming (ObjN), Generation of Action Verbs (GenA) in which patients were asked to overtly say an action associated with a picture and mental simulation of action (MSoA) was investigated by asking subjects to mentally simulate an action related to a depicted object. The distribution of brain activities associated with these tasks whatever DTS was very similar to results of previous studies. The results showed that brain activity related to semantics of action is modified by dopaminergic treatment in PD patients. This cerebral reorganisation concerns mainly motor and premotor cortex suggesting an involvement of the putaminal motor loop according to the "motor" theory of verb processing.

Good recovery from aphasia is also supported by right basal ganglia: a longitudinal controlled PET study. EJPRM-ESPRM 2008 award winner.

AIM: It has long been a matter of debate whether recovery from aphasia after left perisylvian lesion is mediated by perilesional left hemispheric regions or by right homologous areas. To investigate the neural substrates of aphasia recovery, a longitudinal study in patients after a left single perisylvian stroke was performed. METHODS: Thirteen aphasic patients were H2(15)O PET-scanned twice at a one year interval during a word generation task. Patients are divided into two groups according to language performance for the word generation task at PET2. For the Good Recovery (GR) group, patients' performances are indistinguishable from those of normal subjects, while patients from the Poor Recovery (PR) group keep language disorders. Using SPM2, Language-Rest contrast is computed for both groups at both PET stages. Then, Session Effect contrast (TEP2-TEP1>0) is calculated for both groups. RESULTS: For the GR group, the Session Effect contrast shows an increase of activations in the left Postero-Superior Temporal Gyrus PSTG but also in the right thalamus and lenticular nuclei; for PR patients, the right lenticular nucleus activation is more important at PET1 than PET2. CONCLUSIONS: The crucial role of the left temporal activation is confirmed and its increase is linked to behavioural recovery. The role of the right basal ganglia to support good recovery from aphasia is a new finding. Their activation may be more task-dependant and related to inhibition of the right frontal cortex.

[Functional neuroimaging and the treatment of aphasia: speech therapy and repetitive transcranial magnetic stimulation]. / Imagerie fonctionnelle cérébrale et prise en charge thérapeutique de l'aphasie : orthophonie et stimulation magnétique transcrânienne répétitive.

Functional imaging has provided new evidence of the neurobiological impact of the treatment of aphasia, including speech therapy, through the alteration of the activated language neural network. In such a way, speech therapy has proved its impact. The role of each hemisphere is still very unclear. Some of the authors link the left-lateralisation of activations to the therapeutic improvement of language and the right-activated network to a maladaptative strategy, whereas others consider the latter as a useful compensatory network for speech disorders. Repetitive trans-cranial magnetic stimulation (rTMS), first used to determine cortical activity, is now used to directly interfere with cerebral activity. In the years to come, rTMS should be developed as an adjuvant therapy for aphasia.

Right hemisphere activation in recovery from aphasia: lesion effect or function recruitment?

BACKGROUND: Some neuroimaging studies have suggested that specific right hemispheric regions can compensate deficits induced by left hemispheric lesions in vascular aphasia. In particular, the right inferior frontal cortex might take part in lexical retrieval in patients presenting left-sided lesions involving the homologous area. OBJECTIVE: To address whether the involvement of the right inferior frontal cortex is either unique to recovering aphasic patients or present also in other circumstances of enrichment of lexical abilities, i.e., in non-brain-damaged subjects over learning of new vocabulary. METHODS: Ten post-stroke aphasic patients experiencing word finding difficulties were intensively trained to retrieve object names in French over a 4-week period. Twenty healthy subjects were similarly trained to name these items in either Spanish or English, i.e., foreign languages that they learned at school but did not master. By analogy to aphasic patients, healthy subjects had to work out the phonetic/phonologic representations of long-acquired but forgotten words. Brain activity changes were assessed in two H(2)(15)O PET sessions involving picture naming tasks that were performed before and after training. RESULTS: Comparable post-training performance and changes in regional cerebral blood flow including mainly the right insular and inferior frontal regions were found in both groups. CONCLUSION: Our results suggest that enhanced activities in right-sided areas observed in recovering aphasia is not the mere consequence of damage to left-sided homologous areas and could reflect the neural correlates of lexical learning also observed in control subjects.

Neural substrates of spoken language rehabilitation in an aphasic patient: an fMRI study.

Little is known about the neural counterparts of speech therapy in aphasic patients. An fMRI experiment was performed before and after a specific and intensive speech output therapy in RC, a patient with long-lasting speech output deficit following a left-sided ischemic lesion. Overt picture naming and picture/word rhyming were used as activation tasks in RC and 6 control subjects. The naming task concerned the output lexicon deficit to be rehabilitated while rhyming referred to preserved levels of processing and was used to control for repetition effect. The speech therapy program improved naming performance. By comparison to the pattern observed before therapy, the naming task after therapy induced a pattern of activation close to that observed in control subjects, involving left-sided language areas surrounding the lesion. Speech therapy effect was associated with activations in Broca's area and the left supra-marginal gyrus, which might reflect a therapy-induced phonological compensatory strategy for naming.

Lexical therapy and episodic word learning in dementia of the Alzheimer type.

The effect of a language therapy in a group of eight anomic mild patients (the Lexical Therapy group) was assessed by using a 5-month long Lexical Therapy in comparison with an occupational program used in a matched control group (AD; n = 8). The Lexical Therapy group benefited significantly from a language therapy as shown by the naming improvement postintervention. The improvement reached significance only for items that were included in the language therapy protocol and no significant generalization to untreated items was observed. In mild AD patients with anomia and no severe semantic impairment, a reinforcement of the relationship between the form of the object and the corresponding lexical label in episodic long term memory during language therapy may account for the observed lexical improvement.

[Generation of isolated words in normal subjects]. / La génération de mots isolés chez les sujets normaux.

This study aims at analyzing the performance according to age, sex, and educational level in 112 French normal subjects on word generation tests, i.e., time-limited production of a noun or a verb semantically linked to a target "noun" or "verb". The nature of hits (exclusively production of nouns) has moreover been analyzed according to different features of the targets: noun vs verb, names of natural objects vs handmade objects, transitive vs intransitive verbs. Results show 1) a significant effect of age and educational level on performance, 2) a degree of difficulty, the verb/verb production test being significantly more difficult than the three other tests, 3) a convergency effect according to the natural vs handmade dichotomy, as subjects tend to produce, without specific instruction, an item belonging to the same category as that of the stimulus, and 4) object nouns tend to be produced in response to transitive verbs whereas subject nouns are not predominantly produced in response to intransitive verbs.

Hemispheric preponderance in categorical and coordinate visual processes.

Two experiments were conducted to address whether a left hemispheric bias would be observed for categorical processing in both 'what' and 'where' systems (experiment 1) while a reverse bias would characterize coordinate processing whatever the systems (experiment 2). Young normal subjects were tested using divided visual field tasks. The results of experiment 1 indicated that subjects made categorical judgments in both what and where systems faster when stimuli are presented to the left hemisphere. The results of experiment 2 showed a significant interaction between visual field and difficulty of processing coordinate relationships. Indeed, a left-hemisphere advantage was observed when the task required easy processing whereas a right-hemisphere advantage was noted for difficult distinctions either in location (where system) or in lightness (what system). The left-hemisphere advantage we observed for categorization in both systems confirms the Kosslyn's hypothesis (1989) for the where system and suggests that the same left-hemisphere advantage also exists for the what system. Concerning coordinate processing, our findings highlight the influence of processing difficulty on the hemispheric lateralization and evidence a right hemispheric advantage for difficult coordinate processing and a left hemispheric advantage for easy coordinate processing. The results are discussed in terms of possible link between on the one hand difficulty and coordinate processing, and easiness and categorization on the other hand.

Brain correlates of memory processes in patients with dementia of Alzheimer's type: a SPECT Activation Study.

Task-induced changes in regional cerebral blood flow (rCBF) during verbal episodic memory activation were compared in 17 right-handed patients with dementia of the Alzheimer's type (DAT) and 20 healthy volunteers. Regional cerebral blood flow was assessed using single photon emission computed tomography (SPECT) and an injection of 133Xe (xenon, isotope of mass 133) in 21 regions of interest (ROI) during rest, passive listening to 36 words, and memorizing of a 12-word list repeated three times. In healthy subjects, memory-listening comparison showed activation of a distributed system involving several left-sided ROI, especially the posterior inferior frontal region. In patients with DAT, the same pattern of activation was found for listening-rest comparison, and no significant changes were found in memory-listening comparison. During listening compared with rest, significant activation was observed in left-sided hypoperfused regions. A significant correlation between memory performance and rCBF recorded in patients with DAT during the memory task was found only in the right lateral frontal region, a region that was not hypoperfused significantly in patients. The involvement of this region might relate to either retrieval effort or actual performance of patients with DAT on the memory task.

Age related cognitive decline: a clinical entity? A longitudinal study of cerebral blood flow and memory performance.

OBJECTIVES: To evaluate the changes in regional cerebral blood flow (rCBF) and memory performance in patients with age related cognitive decline (ARCD) who did and did not become demented during a follow up period. METHODS: Twenty four patients with ARCD were recruited from an outpatient memory clinic, of whom 18 were followed up over a mean period of two years. Eighteen patients with mild to moderate probable Alzheimer's disease and 18 aged normal controls were followed up over a mean period of three years. Memory performance and rCBF were evaluated quantitatively at inclusion and during follow up, using single photon emission computed tomography with xenon-133 injection and three subtests of the Wechsler memory scale (logical memory, paired associated learning, and digit span). RESULTS: Patients with ARCD showed decreased rCBF and memory performance at initial evaluation compared with controls. Five of them became demented during the follow up period, with further decline in memory and rCBF. At inclusion, the only feature that distinguished these five patients as a group from the remainder was a pronounced temporoparietal asymmetry. The 13 patients with ARCD who did not become demented still exhibited impaired memory and rCBF at follow up, but without any further decline and no increase in flow asymmetry. CONCLUSIONS: Apart from patients in the preclinical phase of Alzheimer's disease, the ARCD category includes non-demented patients who have brain dysfunction that may represent a distinct clinical entity.

[Main syndromes revealed in a consultation specially focusing on memory]. / Principaux syndromes révélés lors d'une consultation spécialisée de la mémoire.

This paper reports our 2-year experience in a memory clinic practice at a University Hospital. During these 2 years, 128 patients with memory complaints were evaluated by a neurologist, a psychiatrist, a geriatrist and a neuropsychologist using a standardized test battery; only 58 of these patients actually presented with objective memory deficits. These memory impairments were mainly observed in patients with neurologic disorders (principally dementia) and in patients with psychiatric disorders (principally depression, major anxiety and psychiatric diseases with troubles of personality). The aim of this memory clinic is to identify the origin of memory disorders, provide a pharmacological treatment when required, propose appropriate assessment and follow up, and diagnose early symptoms of dementia.

Diversity of patterns of improvement in confrontation naming rehabilitation: some tentative hypotheses.

A previous group analysis of the effects of a computerized written naming rehabilitation program revealed global improvement with generalization of benefits to untrained items and to untreated oral naming (Deloche et al., 1992). The present multiple single-case analysis of the data indicates a variety of patterns of improvement and of generalization effects among individual patients. Patterns of relationships between written and oral naming behaviors help to explain the type of improvement that was observed.

Living/non-living dissociation in a case of semantic dementia: a SPECT activation study.

A category-specific dissociation with massive deficits in semantic knowledge of animals and preservation of knowledge of objects was observed in a demented patient with a left inferior temporal cortical atrophy responsible for a deficit of visual semantic processing. When the patient successfully processed the semantic feature of aurally presented object names, a SPECT study showed an activation of the left posterior and middle temporal cortex (Wernicke's area). This haemodynamic pattern was not observed during an unsuccessful processing of animal names that was associated with an activation of the left and right inferior frontal regions. Activation in Wernicke's area probably reflects an adequate matching between auditory lexical input and semantic knowledge for entities with multimodal representations, such as man-made objects. Activation in Broca's area and its right homologous region may correspond to an unsuccessful phonological strategy to evoke semantic features of animals, a category that is mainly visually represented.

Picture confrontation oral naming: performance differences between aphasics and normals.

Oral confrontation naming was compared in 108 normal subjects controlled for education, age, and gender and in 18 aphasic patients for the same set of 115 pictures. Demographic variables influenced both normals' and aphasics' performance. However, the nature of aphasics' misnamings on the one hand and the differential effects of characteristics of pictures and words on normals' and aphasics' responses on the other indicated specific deficits in patients. The classical hypothesis that aphasics' misnamings and the production of word associations by normals should rely on similar mechanisms (Rinnert & Whitaker, 1973) is questioned. Nondominant responses observed in normals accounted for a larger proportion of verbal errors than associates to target words.

Brain functional profiles in formal and semantic fluency tasks: a SPECT study in normals.

SPECT method is used to analyze changes in regional cerebral blood flow in a group of 19 normal subjects during a baseline task (repetition of two words) and two verbal fluency tasks, a semantic fluency and a formal fluency. The semantic fluency task was associated with a relative CBF increase in the right dorso-lateral and medial frontal region when compared with that seen in the baseline condition. No specific activation was found for the formal fluency task compared to that seen in the baseline task. We suggest that the activation of the right frontal region reflects semantic categorization strategies in semantic fluency. The lack of activation of the left frontal region may be due to an activation induced by the nature of the baseline task (i.e., a self-paced repetition task).

[Cognitive evaluation of patients with Alzheimer-type dementia by French revised version of the Hierarchic Dementia Scale]. / L'évaluation cognitive des patients présentant une démence de type Alzheimer par la version française révisée de la hierarchic dementia scale. Echelle hiérarchisée de la démence (EHD).

The revised French version of the Hierarchic Dementia Scale (HDS) was assessed in 88 DAT patients (30 men, 58 women, mean age: 70, MMS from 0 to 26). The HDS consisted of 20 subtests which covered the entire range of cognitive functions; each subtest was hierarchically organized. This scale has been validated by the authors in 149 control subjects (Démonet et al., 1990). The goals of the present study were to validate this scale in DAT patients in comparison with the MMS scores and to specify the cognitive impairments of our pathologic population. Results showed that the scores on the HDS were highly correlated with the MMS scores (p < .0001). Some subtests of the HDS (memory subtests and mental control) allow good discrimination between mild demented patients and controls (sensibility = 80.8 p. 100, specificity = 96 p. 100). Conversely some subtests allowed a cognitive follow-up of patients for whom the MMS was no longer useful (MMS scores from 0 to 10). In conclusion, it appears that this scale is useful for drawing cognitive profile of DAT patients and to approach the heterogeneity of dementia.

Activation of regional cerebral blood flow by a memorization task in early Parkinson's disease patients and normal subjects.

Task-induced changes in regional cerebral blood flow (rCBF) during memory activation were compared in 18 right-handed patients with early Parkinson's disease (PD) and 20 normal volunteers using the same activation paradigm. We used single-photon emission computed tomography and 133Xe in 21 regions of interest during rest, passive listening of a work list, and memorization of another word list, which was followed by a free recall test immediately after completion of the rCBF measurement. The average performance on free recall was not significantly lower in PD patients than in controls. In normal subjects, five left-sided regions (anterior middle frontal, posterior inferior frontal, superior middle temporal, thalamic, and lenticular) showed a significant increase in memorizing compared to passive listening. This pattern of activation suggests the existence of a verbal rehearsal strategy during the memorization task in normals. In PD patients, increases in these regions did not reach significance, whereas significant activations were noted in superior prefrontal regions. Such alterations in the pattern of activation in PD patients, despite a memory performance similar to that of controls are viewed as a consequence of an early dysfunction of the articulatory loop system and of compensatory mechanisms in other parts of the frontal lobe emerging in the early stages of the disease.

Right temporal compensatory mechanisms in a deep dysphasic patient: a case report with activation study by SPECT.

A brain activation study using SPECT and 133Xe in a deep dysphasic patient with left temporal lesion is presented. The activation paradigm consisted of a passive listening to foreign language as baseline, a phoneme monitoring condition and a semantic word monitoring condition. The specific activation of the right middle temporal cortex observed in the semantic condition is congruent with the hypothesis of a compensatory role of the right hemisphere in processing concrete words. This case illustrates the interest of functional imaging for a better understanding of neural mechanisms of functional recovery after brain injury.

The anatomy of phonological and semantic processing in normal subjects.

We assessed brain activation of nine normal right-handed volunteers in a positron emission tomography study designed to differentiate the functional anatomy of the two major components of auditory comprehension of language, namely phonological versus lexico-semantic processing. The activation paradigm included three tasks. In the reference task, subjects were asked to detect rising pitch within a series of pure tones. In the phonological task, they had to monitor the sequential phonemic organization of non-words. In the lexico-semantic task, they monitored concrete nouns according to semantic criteria. We found highly significant and different patterns of activation. Phonological processing was associated with activation in the left superior temporal gyrus (mainly Wernicke's area) and, to a lesser extent, in Broca's area and in the right superior temporal regions. Lexico-semantic processing was associated with activity in the left middle and inferior temporal gyri, the left inferior parietal region and the left superior prefrontal region, in addition to the superior temporal regions. A comparison of the pattern of activation obtained with the lexico-semantic task to that obtained with the phonological task was made in order to account for the contribution of lower stage components to semantic processing. No difference in activation was found in Broca's area and superior temporal areas which suggests that these areas are activated by the phonological component of both tasks, but activation was noted in the temporal, parietal and frontal multi-modal association areas. These constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language.

[Standardization of a modular and hierarchic cognitive evaluation scale applicable to dementia. A French version of the Hierarchic Dementia Scale]. / Etalonnage d'une échelle d'évaluation cognitive de structure modulaire et hiérarchisée applicable aux démences. Version française modifiée de la Hierarchic Dementia Scale.

We tested a revised version of the Hierarchic Dementia Scale (HDS), proposed by Cole and Dastoor (1980), in order to improve its clinical usefulness and to enrich our knowledge about ageing. The scale was built with 20 subtests which covered the entire range of cognitive and motor functions. Each subtest was hierarchically organized so that success in a item implied success in inferior items. This hierarchical principle was time-saving and was validated by Cole and Dastoor. 149 control subjects performed this test. They were equally divided in 4 age-groups (55-64, 65-74, 75-84, 85-97) and 2 educational levels. None of these subjects had previous history of somatic or neuropsychiatric disease. They were completely self-sufficient in daily life. A large part of the controls failed in the most difficult items of some subtests: Learning, Calculation, Mental Control, Drawing, Recall, Similarities, Constructional Praxis. For these subtests, significantly different mean-scores were observed between age-groups and educational levels. However, the influence of each factor was variable from one subtest to another. Moreover, subgroups seem to exist in our population according to specific difficulties in some of these subtests. This study calls for caution in the interpretation of results in demented patients. Comparisons with other psychometric tools remain to be performed. This scale seems to be more useful for the quantification and follow-up of cognitive deficits than for the early diagnosis of dementia. In addition, this scale, which briefly explores many aspects of cognitive functions, seems especially useful to approach the heterogeneity of DAT.