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.

Event-related functional magnetic resonance imaging study of the extrastriate cortex response to a categorically ambiguous stimulus primed by letters and familiar geometric figures.

Functional neuroimaging studies have suggested a specific role of the extrastriate cortex in letter string and visual word form processing. However, this region has been shown to be involved in object recognition and its specificity for the processing of linguistic stimuli may be questioned. The authors used an event-related functional magnetic resonance imaging design with category priming to record the response elicited by the passive viewing of single letters, geometric figures, and of the categorically ambiguous stimulus "O" that pertains to both sets of familiar symbols. Bilateral activations in the extrastriate cortex were found, with a left predominance particularly pronounced for the ambiguous stimulus. Individual analysis of spatial extent and signal intensity showed a priming x stimulus x hemisphere interaction. When primed by the congruous categoric set, a bilateral decrease in activation was observed for letters and geometric figures. The ambiguous stimulus behaved as a letter for the left hemisphere, with decreased activation when primed by letters, whereas in the right hemisphere, an adaptation effect occurred when primed by geometric figures. These priming effects suggest that, for the ambiguous stimulus, letter processing was systematically involved in the left extrastriate cortex. The current results support the existence of a neural substrate for the abstract category of letters.

Within-session and between-session reproducibility of cerebral sensorimotor activation: a test--retest effect evidenced with functional magnetic resonance imaging.

The aim of the current study was to assess the reproducibility of functional magnetic resonance imaging (fMRI) brain activation signals in a sensorimotor task in healthy subjects. Because random or systematic changes are likely to happen when movements are repeated over time, the authors searched for time-dependent changes in the fMRI signal intensity and the extent of activation within and between sessions. Reproducibility was studied on a sensorimotor task called "the active task" that includes a motor output and a sensory feedback, and also on a sensory stimulation called "the passive task" that assessed the sensory input alone. The active task consisted of flexion and extension of the right hand. The subjects had performed it several times before fMRI scanning so that it was well learned. The passive task consisted of a calibrated passive flexion and extension of the right wrist. Tasks were 1 Hz-paced. The control state was rest. Subjects naïve to the MRI environment and non--MRI-naïve subjects were studied. Twelve MRI-naïve subjects underwent 3 fMRI sessions separated by 5 hours and 49 days, respectively. During MRI scanning, they performed the active task. Six MRI-naïve subjects underwent 2 fMRI sessions with the passive task 1 month apart. Three non--MRI-naïve subjects performed twice an active 2-Hz self-paced task. The data were analyzed with SPM96 software. For within-session comparison, for active or passive tasks, good reproducibility of fMRI signal activation was found within a session (intra-and interrun reproducibility) whether it was the first, second, or third session. Therefore, no within-session habituation was found with a passive or a well-learned active task. For between-session comparison, for MRI-naïve or non--MRI-naïve subjects, and with the active or the passive task, activation was increased in the contralateral premotor cortex and in ispsilateral anterior cerebellar cortex but was decreased in the primary sensorimotor cortex, parietal cortex, and posterior supplementary motor area at the second session. The lower cortical signal was characterized by reduced activated areas with no change in maximum peak intensity in most cases. Changes were partially reversed at the third session. Part of the test-retest effect may come from habituation of the MRI experiment context. Less attention and stress at the second and third sessions may be components of the inhibition of cortical activity. Because the changes became reversed, the authors suggest that, beyond the habituation process, a learning process occurred that had nothing to do with procedural learning, because the tasks were well learned or passive. A long-term memory representation of the sensorimotor task, not only with its characteristics (for example, amplitude, frequency) but also with its context (fMRI), can become integrated into the motor system along the sessions. Furthermore, the pattern observed in the fMRI signal changes might evoke a consolidation process.

[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.

Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia.

We have studied the regional cerebral blood flow (rCBF) changes induced by the execution of a finger-to-thumb opposition motor task in the supplementary and primary motor cortex of two groups of parkinsonian patients on L-dopa medication, the first one without L-dopa induced dyskinesia (n = 23) and the other with moderate peak-dose dyskinesia (n = 15), and of a group of 14 normal subjects. Single photon emission tomography with i.v. 133Xe was used to measure the rCBF changes. The dyskinetic parkinsonian patients exhibited a pattern of response which was markedly different from those of the normal subjects and non-dyskinetic parkinsonian patients, with a significant overactivation in the supplementary motor area and the ipsi- and contralateral primary motor areas. These results are compatible with the hypothesis that an hyperkinetic abnormal involuntary movement, like L-dopa-induced peak dose dyskinesia, is due to a disinhibition of the primary and associated motor cortex secondary to an excessive outflow of the pallidothalamocortical motor loop.

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.

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).

Activation of association auditory cortex demonstrated with functional MRI.

Activations in the temporal lobes previously observed using positron emission tomography and auditory stimuli were partially reproduced with functional MRI and echo-planar imaging at 1.5 T in six volunteers performing tone and phoneme monitoring tasks. Verbal processing compared to a tone recognition task significantly activated a cortical area located in the left anterior temporal region (P < 0.02).

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.

Cerebral blood flow correlates of word monitoring in sentences: influence of semantic incoherence. A spect study in normals.

The aim of this study was to assess the cerebral blood flow (CBF) changes induced by the semantic incoherence of sentences whose words were to be monitored by the subjects. According to Marslen-Wilson and Tyler, word processing would be parallel (global) in semantically coherent sentences, and serial (local) in semantically incoherent ones. We hypothesized that, in comparison with the parallel mode, the serial mode of word processing would result in a preponderant activation of the frontal lobes and/or of the left hemisphere, hence in a flow increase in these regions. In addition, one could assume that the increase in task complexity resulting from the breaking of semantic coherence would reinforce the functional links between hemispheres. Furthermore, as interactions between the processing of semantically coherent vs incoherent of verbal materials and the processing of imageable vs non-imageable stimuli was recently suspected, we designed a study combining coherent vs incoherent sentences and imageable vs non-imageable words. The results we obtained in 12 normal volunteers by measuring regional cerebral blood flow by SPECT and IV injection of Xenon 133 during the four experimental conditions, did not allow us to firmly establish our hypotheses. Indeed, we failed to demonstrate any significant CBF changes across conditions and there was no interaction between coherent vs incoherent and imageable vs non-imageable conditions. However, the analysis of the inter-regional correlations pointed to an increase in the functional links between the hemispheres in the incoherent conditions, whatever the imageability.

Cognition and cerebral blood flow in lateralised parkinsonism: lack of functional lateral asymmetries.

Cognitive and cerebral blood flow (CBF) lateral asymmetries have been quantified in 23 right handed patients with lateralised idiopathic Parkinson's disease. Thirteen patients who had predominant right-sided symptoms (RPD) were compared with ten who had predominant left-sided symptoms (LPD). The patient subgroups were matched for age, education, duration of illness, disease severity and medication. Normalised asymmetries scores were calculated from the data obtained with a test battery and SPECT. No correlation was found between laterality of motor Parkinsonian symptoms and cognitive or haemodynamic asymmetry scores.

Quantitative assessment of cerebral blood volume by single-photon emission computed tomography.

We implemented a technique for measuring regional cerebral blood volume using single-photon emission computed tomography and in vivo technetium-99m-labeled red blood cells and then evaluated it in nine normal human volunteers (controls) and seven patients with bilateral occlusion or severe stenosis of the internal carotid artery. We also measured regional cerebral blood flow using single-photon emission computed tomography and intravenous xenon-133 in the same subjects. We studied regional cerebral blood flow, regional cerebral blood volume, and their ratio before and after the intravenous injection of 1 g acetazolamide. Mean +/- SD baseline regional cerebral blood volume was higher in the patients than in the controls (4.1 +/- 0.6 versus 3.2 +/- 0.3 ml/100 g, p less than 0.01), and mean +/- SD baseline regional cerebral blood flow was lower in the patients than in the controls (40.5 +/- 11 versus 55.6 +/- 11 ml/100 g/min, p less than 0.05). Acetazolamide induced similar mean +/- SD increases in regional cerebral blood volume in both the controls and the patients (0.3 +/- 0.1 and 0.3 +/- 0.2 ml/100 g), while the mean +/- SD regional cerebral blood flow reactivity was significantly less in the patients than in the controls (12.6 +/- 7.6 versus 24.5 +/- 9.6 ml/100 g/min, p less than 0.05). Our study shows that single-photon emission computed tomography can provide quantitative estimates of both regional cerebral blood volume and regional cerebral blood flow in humans.

[Cerebral blood volume, endarterectomy and SPECT]. / Volume sanguin cérébral, endartérectomie et SPECT.

Cerebral blood flow and cerebral blood volume were measured and quantified using single photon emission computed tomography before and after unilateral endarterectomy in 3 patients with bilateral severe lesions of the internal carotid artery. These parameters were measured using an intravenous injection of 133 Xenon and 99m Technetium respectively. Before endarterectomy cerebral blood volume was high in all patients suggesting a focal vasodilatation in response to a reduced cerebral perfusion pressure. After endarterectomy a decrease of cerebral blood volume and an increase of cerebral blood flow were observed. These preliminary results confirm that the hemodynamic adaptative mechanisms secondary to carotid occlusion are reversible when the stenosis is removed and demonstrate that these changes can be accurately measured using single photon emission computed tomography. Positron emission tomography was previously considered to be the only method able to quantify cerebral blood volume in man. Single photon emission computed tomography can also be considered a reliable technique to measure both cerebral blood flow and cerebral blood volume. This technique can then be used to assess individual cerebral vascular adaptative states and to evaluate the influence of cerebral hemodynamic changes on stroke occurrence in large longitudinal studies.

Lateral asymmetries in primary degenerative dementia of the Alzheimer type. A correlative study of cognitive, haemodynamic and EEG data, in relation with severity, age of onset and sex.

Cognitive, haemodynamic and EEG lateral asymmetries have been quantified in 20 patients with Primary Degenerative Dementia (PDD) and in 20 age-matched normal volunteers. Normalized asymmetry scores were calculated from the data obtained with a test battery, with SPECT and with quantitative EEG. Significant correlations were found between cognitive, haemodynamic and EEG scores in patients but not in controls. The functional asymmetries correlated to the Mini Mental State (MMS) score, the lowest MMS values being observed in patients with right hemisphere predominant impairment. Besides, in these patients, a significant correlation was observed between age at onset and MMS score so that, in this subgroup only, the earlier the onset the more severe the disease. Finally, the prevalence of pronounced functional asymmetry seemed to be higher in our male patients. Our study shows that lateral asymmetries are frequent in patients with PDD and that preferential lateralization of the abnormalities should be given further attention, especially with regards to age, sex and overall severity.

Measurement of cerebral circulation time in man.

A simple, inexpensive method for measuring the cerebral circulation time (CCT) was developed. The CCT was considered to be equal to the time that an intravenously injected bolus of sodium pertechnetate Tc 99m took to go from the subclavian artery to the posterior venous confluence. The dilution curves were externally recorded at these two vessels. Particular attention was given to the curve treatment. The computer programmes were specially conceived in order to detect and, if possible, correct the experimental curve defects. Several reliability criteria were also defined in order to test the validity of each measurement. From a physiological point of view, the CCT is equal to the ratio of the global cerebral blood volume to the global cerebral blood flow. Thus, it can be widely applied in clinical research. For example, in a study of the relationship between CCT and age, sex and light cerebrovascular impairment, the technique was sensitive enough to discriminate between healthy subjects and patients suffering from-transient ischemic attack, or regressive stroke, and to show the action of a drug on the cerebral circulation in such patients.