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Biomedical subjects

J C Baron

Publications and source records attributed to J C Baron.

At least 19 recordsLinked to original sources

Mapping the relative contribution of gray matter activity vs. volume in brain PET: a new approach.

Interpretation of brain positron emission tomography (PET) in terms of function vs. structure is ambiguous owing to the partial volume effect (PVE). Therefore, observed differences in tracer distribution could reflect differences in either activity or volume, a problem that applies principally to gray matter (GM) since white matter (WM) virtually always has uniform activity. To assess the contribution of GM volume vs. activity, we implemented a method to directly compare PET images with underlying structure, and applied it to resting-state (18)Fluoro-deoxy-glucose-PET (FDG) of healthy subjects. Methods. Average GM and WM PVE-corrected mean FDG uptake values were applied onto co-registered segmented magnetic resonance imaging data sets to generate a "virtual PET" in which activity is proportional to GM volume and resolution set to that of PET. The raw PET and virtual PET values were then compared across the sample of subjects, first voxel-wise to detect clusters with significant activity-volume mismatch, and second within regions-of-interest (ROI) to quantify mismatches between unsmoothed voxel values. Results. Relative to volume, there was significant hyperactivity of most GM structures of the dorsal brain-except the thalamus-and significant hypoactivity of the temporal lobe, hippocampal region, and cerebellum, consistent across the voxel- and ROI-based analyses. Conclusion. As applied to normals, our method documented the expected contribution of functional activity independently of local differences in GM volume in the normal pattern of FDG uptake, and disclosed marked heterogeneities in functional activity per unit GM volume among structures. This generic method should find applications in pathological states as well as for other PET and SPECT radiotracers.

Brain↗

Global cognitive impairment should be taken into account in SPECT-neuropsychology correlations: the example of verbal memory in very mild Alzheimer's disease.

PURPOSE: To examine the impact of severity of global cognitive impairment on SPECT-neuropsychology correlations, we correlated a verbal memory test with brain perfusion in patients with very mild Alzheimer's disease (AD), taking into account the Mini-Mental State Examination (MMSE) score as an index of global cognitive impairment. METHODS: Twenty-nine outpatients (mean age 78.2+/-5.5 years) affected by very mild, probable AD underwent brain SPECT with 99mTc-ethylcysteinate dimer and a word list learning test. SPM99 was used for voxel-based correlation analysis after normalisation to mean cerebellar counts (height threshold: p<0.01). In a first analysis, only age and years of education were inserted as nuisance covariates, while in a second analysis the MMSE score was inserted as well. RESULTS: In the first analysis, two clusters of significant correlation were found in both hemispheres, mainly including regions of the right hemisphere, such as the inferior parietal lobule, the middle temporal gyrus and the posterior cingulate. Significant correlation in the left hemisphere was observed in the lingual lobule, the parietal precuneus and the posterior cingulate. After taking into consideration the MMSE, the largest cluster of correlation was found in the left hemisphere, including the parietal gyrus angularis, the posterior cingulate and the middle temporal gyrus. CONCLUSION: The wide differences observed between the correlations achieved with and without taking into account the MMSE score indicate that severity of global cognitive impairment should be considered when searching for brain perfusion-neuropsychology correlations. In the present case, this strategy resulted in correlations that more closely matched neuropsychological models of verbal memory deficit.

Aged↗

[Ureteral access].

Knowledge of the different surgicaL approaches of the ureter remains necessary for the urologist as many ureterat diseases cannot be treated by simple urological access (endo-urology). Open and Laparoscopic accesses of the 4 parts of the ureter (lombar, iliac, pelvic and terminal parts) are described.

Humans↗

[Quantitative relationships between ADC and perfusion changes in acute ischemic stroke using combined diffusion-weighted imaging and perfusion MR (DWI/PMR)].

UNLABELLED: MR-based diffusion- and perfusion-weighted imaging (DWI/PWI) has become the standard imaging technique to assess the individual brain pathophysiological status in acute ischemic stroke. The finding of a "mismatch" with larger PWI than DWI abnormality is thought to reflect the presence of tissue at-risk of infarction, i.e., penumbra. However, there has been no detailed study of the quantitative relationships between perfusion and diffusion changes in stroke patients. According to the experimental concept of penumbra, the ADC would be expected to remain unchanged despite decreasing perfusion until a critical threshold is reached. We have tested this hypothesis directly in man. METHODS: DWI/PWI was performed in 7 patients with MCA territory stroke within 4-10 hrs from onset. Mismatch was defined on diffusion and rMTT maps, and circular ROIs were positioned within the ADC lesion (D), the mismatch area (M), and the normal appearing cortex (N); mirror ROIs were also obtained, and affected/unaffected ratios for ADC and rCBF were computed for each ROI. RESULTS: The mean (+/-1 SD) ADC ratios were 0.60 +/- 0.09, 0.95 +/- 0.10 and 1.02 +/- 0.04 in L, M and N, respectively; the corresponding rCBF ratios were 0.32 +/- 0.12, 0.75 +/- 0.14 and 0.97 +/- 0.09, respectively. The relationship was non-linear, with the rCBF but not the ADC ratio for M being significantly lower (p < 0.01) than that for N. A threshold for decline in ADC was apparent around 0.50 rCBF ratio. COMMENT: These results directly document in man that the ADC declines only after hypoperfusion has reached a certain degree (about 50%), consistent with the concept of the ischaemic penumbra.

Acute Disease↗

[Arguments for deciding to change treatment in benign prostatic hyperplasia].

Insufficient efficacy above all, but also the appearance of side effects or the occurrence of complications may motivate a change in the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (HBP). In terms of efficacy, surgery remains superior to all medical treatments including alphablockers which are the most active. 5-alpha-reductase inhibitors have a slow efficacy which is all the more marked when the prostatic volume is large. Phytotherapy has a slight activity which is higher than that of placebo. Drug combinations are currently being studied and, although a benefit has been shown in certain publications, their clinical efficacy remains to be specified. They may become an alternative in case of failure of single-agent therapy to prevent or delay surgery. The incidence of side effects is low and varies with the treatment used and within a same therapeutic class. With alphablockers for instance, orthostatic hypotension, which is the main side effect, varies from 1% to 8% approximately depending on the study and molecule. The side effects of 5-alpha-reductase inhibitors are mainly sexual disorders, observed in 1 to 4% of cases approximately. Hence, the occurrence of a drug side effect causing treatment discontinuation should incite a change of molecule, even within the same class for alphablockers. On the other hand, if complications of HBP occur, it is then necessary to resort to surgery.

Humans↗

Rapidly reversible dementia in cerebral amyloid inflammatory vasculopathy.

This report discusses a biopsy proven case of cerebral amyloid angiopathy, with additional prominent vascular inflammatory features, characterized by a rapidly progressive dementia and leukoencephalopathy, where the clinical and radiological abnormalities resolved rapidly with minimal therapeutic intervention. We propose the term cerebral amyloid inflammatory vasculopathy (CAIV) to describe this condition.

Adrenal Cortex Hormones↗

Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET.

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.

Aged↗

Stroke: imaging and differential diagnosis.

Structural and vascular imaging helps to differentiate haemorrhagic from acute ischemic stroke (AIS) and rule out non-stroke causes, as well as identify specific subtypes of stroke such as carotid dissection and venous thrombosis. However, it is negative in most AIS patients within 3-6 hrs of onset and thus does not allow efficient patient classification for management purposes. Physiologic neuroimaging with PET, SPECT and combined diffusion- and perfusion-weighted MR gives access to tissue perfusion and cell function/homeostasis. It has near 100% sensitivity in AIS, even in small cortical or brainstem strokes. In middle-cerebral artery (MCA) stroke, physiologic imaging also allows pathophysiological differentiation into four tissue subtypes: i) already irreversibly damaged ("core"); ii) severely hypoperfused ("penumbra"), which represents the main target for therapy; iii) mildly hypoperfused ("oligaemia"), not at risk of infarction unless secondary complications arise; and iv) reperfused/hyperperfused. PET studies have evidenced the penumbra in man, shown its largely cortical topography, documented its anticipated impact on both acute-stage neurological deficit and recovery therefrom, and shown its persistence up to 16 hrs after stroke onset in some patients. However, some patients acutely exhibit extensive irreversible damage, which places them at considerable risk of malignant MCA infarction, and others early spontaneous reperfusion, which is almost invariably associated with rapid and complete recovery. Thrombolytics and/or neuroprotective agents would therefore be expected to benefit, and hence should ideally be reserved to, only those patients in whom a substantial penumbra is documented by physiologic neuroimaging, even perhaps beyond the 3 to 6 hrs rule. In addition, excluding from thrombolytic therapy those patients with substantial necrotic core should avoid many instances of symptomatic haemorrhagic transformations. Finally, patients with extensive core might benefit from early decompressive surgery, and those with early extensive reperfusion from anti-inflammatory agents. Overall, therefore, the pathophysiologic heterogeneity underlying AIS may account for both the complications from thrombolysis and the limited success of clinical trials of neuroprotective agents, despite apparent benefit in the laboratory. Pathophysiological diagnosis as afforded by neuroimaging should now be incorporated in the design of clinical trials as well as in the routine management of stroke.

Brain Mapping↗

Excitotoxic lesions of the rhinal cortex in the baboon differentially affect visual recognition memory, habit memory and spatial executive functions.

To specify the functional role of the rhinal cortex, baboons with bilateral excitotoxic lesions of the rhinal cortex (RH group) were tested on a series of computerized memory and learning tasks. Preoperatively, they were trained to and then tested on a delayed nonmatching-to-sample (DNMS) task with trial-unique stimuli. Postoperatively, this visual recognition memory task was given twice. As compared to a sham-operated group, the RH group showed good retention of rule learning and were unimpaired on the Delay memory subtest. Performance on the List Length memory subtest was, however, severely impaired at both postoperative evaluations, with a significant negative correlation between cognitive performance and neuronal loss in rhinal areas. Visual habit memory and spatial working memory were assessed postoperatively only, using a concurrent discrimination learning task and both a delayed-response task (with a two- and four-location choice) and a delayed alternation task, respectively. The RH group was unimpaired on the first two tasks and was even faster than the controls in learning the delayed-response task with four locations. Finally, most RH baboons failed to learn the delayed alternation task within the limits of testing. These results indicate that neuronal loss in the rhinal cortex is sufficient to impair visual recognition memory, and extend the implication of this area to spatial executive functions. Furthermore, the observation of impaired recognition memory and executive processes with preserved procedural memory and retrograde memory suggests that damage to the rhinal cortex probably participates in the cognitive deficits typical of the early stages of Alzheimer's disease.

Animals↗

Sequential activation brain mapping after subcortical stroke: changes in hemispheric balance and recovery.

We prospectively studied 5 patients while they were recovering from left-sided subcortical stroke affecting the cortico-spinal tract, and examined them twice with H(2)(15)O-PET over several months while performing an identical task with the affected hand. Concomitant motor recovery was assessed by measuring the number of thumb-to-index tappings performed in 15 s at each PET session. Across patients, the hemispheric activation balance tended to shift over time toward the unaffected hemisphere, but the magnitude of this shift was highly variable from patient to patient and significantly correlated with recovery. Thus, in subcortical stroke, a shift of activation balance towards the unaffected hemisphere appears associated with lesser initial recovery and, conversely, the more this physiological balance is maintained over time the better the recovery.

Brain Mapping↗

Visual priming within and across symbolic format using a tachistoscopic picture identification task: a PET study.

The present work was aimed at characterizing picture priming effects from two complementary behavioral and functional neuroimaging (positron emission tomography, PET) studies. In two experiments, we used the same line drawings of common living/nonliving objects in a tachistoscopic identification task to contrast two forms of priming. In the within-format priming condition (picture-picture), subjects were instructed to perform a perceptual encoding task in the study phase, whereas in the cross-format priming condition (word-picture), they were instructed to perform a semantic encoding task. In Experiment 1, we showed significant priming effects in both priming conditions. However, the magnitude of priming effects in the same-format/perceptual encoding condition was higher than that in the different-format/semantic encoding condition, while the recognition performance did not differ between the two conditions. This finding supports the existence of two forms of priming that may be subserved by different systems. Consistent with these behavioral findings, the PET data for Experiment 2 revealed distinct priming-related patterns of regional cerebral blood flow (rCBF) decreases for the two priming conditions when primed items were compared to unprimed items. The same-format priming condition involved reductions in cerebral activity particularly in the right extrastriate cortex and left cerebellum, while the different-format priming condition was associated with rCBF decreases in the left inferior temporo-occipital cortex, left frontal regions, and the right cerebellum. These results suggest that the extrastriate cortex may subserve general aspects of perceptual priming, independent of the kind of stimuli, and that the right part of this cortex could underlie the same-format-specific system for pictures. These data also support the idea that the cross-format/semantic encoding priming for pictures represents a form of lexico-semantic priming subserved by a semantic neural network extending from left temporo-occipital cortex to left frontal regions. These results reinforce the distinction between perceptual and conceptual priming for pictures, indicating that different cerebral processes and systems are implicated in these two forms of picture priming.

Adult↗

Contributions of frontal and medial temporal regions to verbal episodic memory: a PET study.

Using PET, subtraction and correlation analysis were jointly employed to determine the specific and complementary contributions of frontal and medial temporal regions to verbal episodic encoding and retrieval processes. Subtraction analysis highlighted prefrontal rCBF increases which were predominantly left-sided during intentional encoding and exclusively right-sided during retrieval, the latter being moreover associated with bilateral precuneus activation. However, significant correlation between rCBF values obtained during intentional encoding and performance scores obtained during retrieval concerned, among other regions, the left parahippocampal gyrus, which indicated that the higher the neuronal activity in this medial temporal region during encoding, the better the retrieval performance.

Adult↗

Entorhinal cortex disruption causes memory deficit in early Alzheimer's disease as shown by PET.

Voxel-based mapping of the correlations between cognitive scores and resting-state brain glucose utilization measured by PET has recently emerged as a novel way to reveal in living patients with Alzheimer's disease (AD) the neural systems whose disruption underlies particular neuropsychological, especially mnemonic, deficits. We have now applied this approach using a novel cognitive paradigm designed to selectively assess verbal episodic memory, and show that in early AD disruption of the left entorhinal cortex underlies this memory deficit, consistent with post mortem data showing that this brain area is affected earliest and most severely by tau pathology in AD.

Aged↗

Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.

Adult↗

In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease.

Up till now, the study of regional gray matter atrophy in Alzheimer's disease (AD) has been assessed with regions of interest, but this method is time-consuming, observer dependent, and poorly reproducible (especially in terms of cortical regions boundaries) and in addition is not suited to provide a comprehensive assessment of the brain. In this study, we have mapped gray matter density by means of voxel-based morphometry on T1-weighted MRI volume sets in 19 patients with mild AD and 16 healthy subjects of similar age and gender ratio and report highly significant clusters of gray matter loss with almost symmetrical distribution, affecting mainly and in decreasing order of significance the medial temporal structures, the posterior cingulate gyrus and adjacent precuneus, and the temporoparietal association and perisylvian neocortex, with only little atrophy in the frontal lobe. The findings are discussed in light of previous studies of gray matter atrophy in AD based either on postmortem or neuroimaging data and in relation to PET studies of resting glucose consumption. The limitations of the method are also discussed in some detail, especially with respect to the segmentation and spatial normalization procedures as they apply to pathological brains. Some potential applications of voxel-based morphometry in the study of AD are also mentioned.

Aged↗

An ERD mapping study of the neurocognitive processes involved in the perceptual and semantic analysis of environmental sounds and words.

The aim of this paper was to investigate and compare the EEG mechanisms underlying the perceptual and semantic processes involved in environmental and language sounds perception by manipulating the degree of identification of sounds and using the ERD (event-related desynchronization) method in healthy subjects. Four types of stimuli were analyzed: meaningful environmental sounds, meaningless sounds, words and non-words. We report many similarities in the ERDs and ERSs (event-related synchronizations) patterns among all stimuli, with: (i) similar time-course of ERDs and ERSs between meaningful environmental sounds and words, and between meaningless sounds and non-words; (ii) similar topography of the maximal ERDs for meaningful environmental sounds, words and non-words; and (iii) same right posterior ERSs for all four stimuli. However, differences were also observed: (i) in time-course, with earlier ERSs for meaningless than meaningful stimuli, whether environmental or verbal; and (ii) in topography, with ERDs predominating in left and right hemisphere channels for meaningful and meaningless environmental sounds, respectively; (iii) ERSs predominating in the left temporal channel for non-words and in the left posterior and right frontal channels for meaningless sounds. The results of this study suggest that meaningful stimuli involve greater and longer-lasting semantic processes than meaningless stimuli, while the occurrence of ERSs for the latter points to the possible involvement of an inhibitory processing of semantic representations. Finally, the findings concerning the comparison between verbal and non verbal stimuli suggest the involvement of left-lateralized phonological and semantic processes for the former, and more distributed neurocognitive processes in both hemispheres for the latter although with predominant left laterality for their semantic processing.

Adult↗

A survey of neuroimaging research in European neurological departments.

In the international neurological literature, neuroimaging research plays an important role. Neuroimaging techniques are also of steadily increasing importance for clinical diagnosis and treatment monitoring. Therefore, neuroimaging research activities were surveyed by a questionnaire, which was completed by 100 neurological centres across Europe. It showed that most groups use magnetic resonance imaging (MRI), fMRI, computerized tomography (CT) and single photon emission computerized tomography (SPECT). Positron emission tomography (PET) and ultrasound are also employed by nearly half of the centres. Neuroimaging research involves co-operation amongst typically five to 10 disciplines. Cerebrovascular disease, dementia, cognitive disorders, epilepsy, movement disorders, brain tumours and multiple sclerosis are frequently being studied. Many groups rely on small budgets, have few full-time scientists and limited access to expensive resources. There is little exchange of scientists amongst laboratories. It was felt that funding and co-operation needed improvement in order to maintain a high standard in neuroimaging research.

Data Collection↗

Guidance for the preparation of neurological management guidelines by EFNS scientific task forces.

The aim of an EFNS neurological management guideline is to provide guidance for clinical neurologists, other health care professionals and health care providers about important aspects of management of neurological disease. It represents the view of an expert task force appointed by the chairperson of the scientific committee with the agreement of the chairperson of a Scientist Panel. It will be a peer-reviewed statement of minimum desirable standards for the guidance of practice based on the best available evidence. It is not intended to have legally binding implications in individual cases.

Humans↗