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ABSTRACT: Alzheimer's disease (AD) is characterized by a progressive loss of controlled cognitive processes, and neuroimaging studies at early stages of AD provide an opportunity to tease out the neural correlates of controlled processes. Accordingly, controlled and automatic memory performance was assessed with the Process Dissociation Procedure in 50 patients diagnosed with questionable Alzheimer's disease (QAD). The patients' brain glucose metabolism was measured using FDG-PET. After a follow-up period of 36 months, 27 patients had converted to AD, while 23 remained stable. Both groups showed a similar decrease in controlled memory processes but preserved automatic processes at entry into the study. Voxel-based cognitive and metabolic correlations showed that a decrease in controlled memory processes was preferentially correlated with lower activity in the dorsomedial prefrontal and posterior cingulate cortices in very early AD patients. In stable QAD patients, reduced controlled performance in verbal memory correlated with impaired activity in the left anterior hippocampal structure. The results demonstrate the central role of a medial frontal-posterior cingulate network for controlled processing of episodic memory in the early stages of AD.
Journal of Alzheimer's disease: JAD 02/2010; 20(2):547-60. · 3.74 Impact Factor
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ABSTRACT: Although the penumbra can be saved by early reperfusion, in the rat it is consistently affected by selective neuronal loss. Mapping selective neuronal loss in the living primate would be desirable.
Five young adult baboons underwent (15)O positron emission tomography for cerebral blood flow, cerebral oxygen consumption, and oxygen extraction fraction mapping at baseline and serially during and after 20-hour temporary middle cerebral artery occlusion. At approximately day 30, (11)C-flumazenil (FMZ), a potential positron emission tomography marker of selective neuronal loss, and structural magnetic resonance-based infarct mapping were obtained, and the brain was perfused-fixed. Reduced FMZ binding in noninfarcted cortical middle cerebral artery areas was searched voxel-wise, and specific binding was assessed using compartmental modeling of FMZ time-activity curves.
Visual inspection revealed reduced late FMZ uptake in the affected cortical territory, extending well beyond the infarct. Accordingly, the incidence of selected voxels was greater than chance, documenting mildly but significantly reduced FMZ uptake and specific binding. Serial (15)O positron emission tomography revealed moderately severe acute ischemia followed by reperfusion. Histopathology documented only mild neuronal changes in or near the affected areas.
We document moderate but definite late FMZ binding decrements in noninfarcted cortical areas in the baboon, consistent with previous rat and human studies. These were acutely characterized by moderate ischemia followed by reperfusion, consistent with neuronal damage from ischemic or reperfusion injury in the salvaged at-risk tissue. Only mild histopathological changes subtended these FMZ alterations suggesting subtle processes such as isolated dendrite or synapse loss. Whether these changes impact on clinical outcome deserves studying because they may be targeted by specific neuroprotection.
Stroke 04/2008; 39(3):991-9. · 5.73 Impact Factor
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Jean-Noël Talbot,
Fabrice Gutman,
Virginie Huchet,
Khaldoun Kerrou,
Sona Balogova, Nacer Kerrouche,
Françoise Montravers,
Dany Grahek,
Olivier Cussenot,
Bernard Gattegno,
Philippe Thibault
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ABSTRACT: In prostate cancer, use of FDG, the radiopharmaceutical currently most widely used in oncology, is limited to the most aggressive cancers and, in the absence of another tracer, to attempting to localise occult recurrences detected biochemically (elevated PSA serum levels). Four other PET tracers are currently suggested in various situations of prostate cancer development: for guiding biopsies, for diagnosis and staging of the primary cancer and of local or metastatic recurrences, especially in bone, and for localizing occult biochemical recurrence. This article is illustrated by cases summarising our experience with fluoromethylcholine-(18F) and PET/CT. They cover a wide spectrum of clinical settings: localisation of intraprostatic neoplastic lesions, initial staging, monitoring treatment by ultrasound, detection of occult recurrences and characterisation of images on conventional imaging modalities, which are questionable or difficult to interpret.
La Presse Médicale 01/2008; 36(12 Pt 2):1794-806. · 0.67 Impact Factor
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ABSTRACT: We used principal component analysis to decompose functional images of patients with AD in orthogonal ensembles of brain regions with maximal metabolic covariance. Three principal components explained 38% of the total variance in a large sample of FDG-PET images obtained in 225 AD patients. One functional ensemble (PC2) included limbic structures from Papez's circuit (medial temporal regions, posterior and anterior cingulate cortex, thalamus); its disruption in AD patients was related to episodic memory impairment. Another principal component (PC1) illustrated major metabolic variance in posterior cerebral cortices, and patients' scores were correlated to instrumental functions (language and visuospatial abilities). PC3 comprised frontal, parietal, temporal and posteromedial (posterior cingulate and precuneus) cortices, and patients' scores were related to executive dysfunction and global cognitive impairment. The three main metabolic covariance networks converged in the posterior cingulate area that showed complex relationships with medial temporal structures within each PC. Individual AD scores were distributed as a continuum along PC axes: an individual combination of scores would determine specific clinical symptoms in each patient.
Neurobiology of aging 08/2007; 30(2):186-97. · 5.94 Impact Factor
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ABSTRACT: The brain metabolic pattern of vascular dementia (VaD) remains poorly characterized. Univariate voxel-based analysis ignores the functional correlations among structures and may lack sensitivity and specificity. Here, we applied a novel voxel-based multivariate technique to a large ((18)F)2-fluoro-2-deoxy-D-glucose positron emission tomography data set. The sample consisted of 153 subjects, one-third each being probable subcortical VaD, probable Alzheimer disease (AD) (matched for Mini-Mental-State examination (MMSE) and age), and normal controls (NCs). We first applied principal component (PC) analysis and removed PCs significantly correlated to age. The remainders were used as feature vectors in a canonical variate analysis to generate canonical variates (CVs), that is, linear combinations of PC-scores. The first two CVs efficiently separated the groups. CV(1) separated VaD from AD with 100% accuracy, whereas CV(2) separated NC from demented subjects with 72% sensitivity and 96% specificity. Images depicting CV(1) and CV(2) showed that lower metabolism differentiating VaD from AD mainly concerned the deep gray nuclei, cerebellum, primary cortices, middle temporal gyrus, and anterior cingulate gyrus, whereas lower metabolism in AD versus VaD concerned mainly the hippocampal region and orbitofrontal, posterior cingulate, and posterior parietal cortices. The hypometabolic pattern common to VaD and AD mainly concerned the posterior parietal, precuneus, posterior cingulate, prefrontal, and anterior hippocampal regions, and linearly correlated with the MMSE. This study shows the potential of voxel-based multivariate methods to highlight independent functional networks in dementing diseases. By maximizing the separation between groups, this method extracted a metabolic pattern that efficiently differentiated VaD and AD.
Journal of Cerebral Blood Flow & Metabolism 10/2006; 26(9):1213-21. · 5.01 Impact Factor
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Eric Salmon, Nacer Kerrouche,
Karl Herholz,
Daniela Perani,
Vjera Holthoff,
Bettina Beuthien-Baumann,
Christian Degueldre,
Christian Lemaire,
André Luxen,
Jean-Claude Baron,
Fabienne Collette,
Gaëtan Garraux
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ABSTRACT: Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research program the principal brain clusters characterized by a common variability in cerebral metabolism in FTD. Seventy patients with frontal variant (fv) FTD were selected according to international clinical recommendations; principal component analysis (PCA) was performed on FDG-PET metabolic images, looking for covariance clusters in this large population. A first metabolic cluster included most of the lateral and medial prefrontal cortex, bilaterally; PC1 scores correlated with performances on memory and executive neuropsychological tasks. Moreover, FDG-PET images in fv-FTD were further characterized by a metabolic covariance in two clusters comprising the subcallosal medial frontal region, the temporal pole, medial temporal structures and the striatum, separately in the left and in the right hemisphere. The study provides original data-driven arguments for metabolic involvement of separate brain clusters in the rostral limbic system, corresponding to pathological poles differentially affected in each FTD patient.
NeuroImage 05/2006; 30(3):871-8. · 5.89 Impact Factor
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ABSTRACT: Thrombolysis within 3 to 6 hours of symptom onset is recommended therapy for acute middle cerebral artery (MCA) stroke, but recent imaging studies in humans suggest that the penumbra may last much longer in some patients. It is therefore important to study the events that take place with occlusions that last longer than 6 hours. Based upon positron emission tomography (PET), the tissue with high oxygen extraction fraction (OEF) is at risk of infarction. In a previous sequential PET study in anesthetized baboons, we documented that when reperfusion was initiated at 6 hours after MCA occlusion, the region with the acutely highest OEF was not incorporated within the final magnetic resonance imaging (MRI)-defined infarct, suggesting reperfusion prevented such demise. In agreement with this hypothesis, we report here using the same sequential PET paradigm with final chronic-stage volume MRI that a 20-hour MCA occlusion resulted in, on average, 36% of the highest OEF area being recruited into the final infarct. We also found that the portion of the highest OEF area that went on to infarct had at the earliest time-point significantly lower cerebral blood flow and cerebral oxygen metabolism (mean reductions relative to unoccluded side, 56% and 32%, respectively) than the portion that did not (41% and 11%, respectively) and that some reperfusion occurred in the latter at second time-point, that is, before recanalization. Thus, apart from duration of occlusion, the fate of the at-risk tissue is predicated by the initial severity of the ischemia as well as by early secondary events such as partial spontaneous reperfusion.
Journal of Cerebral Blood Flow & Metabolism 06/2004; 24(5):495-508. · 5.01 Impact Factor
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ABSTRACT: The aim of this study is to examine the effects of sleep deprivation during the first or second half of the night on episodic memory consolidation. Episodic memory is defined as memory for events located in time and space. It is also characterized by autonoetic consciousness, which gives a subject the conscious sensation of traveling back in time to relive the original event and forward into the future.
Consolidation of episodic information was tested after 4-hour retention intervals, which followed learning and occurred during either the early or late half night, respectively dominated by slow wave sleep (SWS) or rapid eye movement (REM) sleep, or corresponding periods of wakefulness.
Data collection occurred in the sleep laboratory.
Forty-three young healthy subjects: 9 men and 34 women, age ranging from 18 to 26 years (mean 20.18 +/- 1.94 years) were included in this study.
Waking after a 4-hour retention interval filled with early or late sleep, or 4-hour sleep deprivation, during early or late period of night.
The cognitive task, named the What-Where-When test, was specially designed to assess factual, spatial, and temporal components of episodic memory. This task was associated with the Remember/Know paradigm to assess autonoetic consciousness. We measured performance on immediate free recall, delayed free recall (after a 4-hour interval of wakefulness or sleep), and delayed recognition. We also calculated a forgetting rate for each feature (factual, spatial, and temporal) and, for the recognition task, scores of autonoetic consciousness (R responses). REM-sleep deprivation was associated with significantly lower recall of spatial information compared to SWS deprivation (P < .01) or late sleep (P < .05) conditions. REM-sleep deprivation was also associated with a higher forgetting rate of temporal information as compared to the early sleep condition (P< .01). Finally, REM-sleep deprivation led subjects to give significantly fewer R responses, indicative of true memories, as compared to SWS deprivation (P < .05).
These results suggest that consolidation of truly episodic memories mainly involves REM sleep.
Sleep 05/2004; 27(3):395-401. · 5.05 Impact Factor
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ABSTRACT: Increased semantic priming effects (hyperpriming) are sometimes observed in Alzheimer's disease (AD) and in normal aging. Whereas the processes underlying this phenomenon are now well understood in AD, the interpretation is much more woolly in normal aging. To explore semantic priming, the authors used a lexical decision task in which the influence of attention and cognitive slowing was controlled. To explore the semantic organization, the words had coordinate (tiger-lion) or attribute relations (zebra-stripes). Priming scores of 21 older and 20 young participants were equivalent in the 2 conditions. These results reflect the integrity of semantic memory with normal aging and call into question some investigations showing hyperpriming for older participants; this may instead be an artifact of a general slowing effect.
Neuropsychology 11/2003; 17(4):594-601. · 3.82 Impact Factor
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ABSTRACT: Principal component analysis (PCA) is a well-known technique for reduction of dimensionality of functional imaging data. PCA can be looked at as the projection of the original images onto a new orthogonal coordinate system with lower dimensions. The new axes explain the variance in the images in decreasing order of importance, showing correlations between brain regions. We used an efficient, stable and analytical method to work out the PCA of Positron Emission Tomography (PET) images of 74 normal subjects using [(18)F]fluoro-2-deoxy-D-glucose (FDG) as a tracer. Principal components (PCs) and their relation to age effects were investigated. Correlations between the projections of the images on the new axes and the age of the subjects were carried out. The first two PCs could be identified as being the only PCs significantly correlated to age. The first principal component, which explained 10% of the data set variance, was reduced only in subjects of age 55 or older and was related to loss of signal in and adjacent to ventricles and basal cisterns, reflecting expected age-related brain atrophy with enlarging CSF spaces. The second principal component, which accounted for 8% of the total variance, had high loadings from prefrontal, posterior parietal and posterior cingulate cortices and showed the strongest correlation with age (r = -0.56), entirely consistent with previously documented age-related declines in brain glucose utilization. Thus, our method showed that the effect of aging on brain metabolism has at least two independent dimensions. This method should have widespread applications in multivariate analysis of brain functional images.
Human Brain Mapping 02/2003; 18(1):13-21. · 5.88 Impact Factor
