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J C Baron

Publications and source records attributed to J C Baron.

At least 55 records · Page 3Linked to original sources
PubMed1999

High temporal resolution dynamic mapping of instantaneous EEG amplitude modulation after tone-burst auditory stimulation.

A new method of instantaneous EEG analysis based on amplitude modulation (AM-EEG) was applied to analyze the AM-EEG changes in the alpha frequency band (8.20-12.89 Hz) for successive 5 ms epochs. Repeated auditory tone-burst stimuli (of 220 ms duration) were presented at fixed 2.56 second intervals to 12 attending right-handed young female volunteers, who were EEG-recorded over 19 EEG channels at 200 Hz sampling frequency. The time-course of functional activation was characterized in terms of percent decrease in instantaneous amplitude modulation, as compared to baseline, in analogy with the classical event-related desynchronization paradigm. A dynamic sequence of the successive 122 AM-EEG maps obtained for the 610 ms from beginning of tone-burst was stored and later animated on PC microcomputer. Topological changes among successive maps were extracted into 40 specific AM-EEG maps. Early left temporal and centro-temporal activation was observed, followed first by strong bilateral frontal, and then by left temporal activation. These changes induced by a warning tone-burst are discussed in terms of functional neurophysiology. The present method therefore allows an improved time-resolution for functional brain activation paradigms.

Acoustic Stimulation↗
PubMed1999

Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study.

The central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well-known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age- and sex-matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III-R criteria, and 10 age- and gender-matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C-flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger's and Covi's scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F-values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety-score-PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across-group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety.

Adolescent↗
PubMed1999

Voxel-based mapping of irreversible ischaemic damage with PET in acute stroke.

Objective mapping of irreversible tissue damage in the acute stage of ischaemic stroke would be useful for prognosis and in assessing the efficacy of therapeutic manoeuvres in impeding extension of infarction. From our database of 30 patients studied with 15O-PET within 5-18 h after onset of first-ever middle cerebral artery territory stroke, we extracted a subgroup of 19 survivors (age 74.6 +/- 8.5 years) in whom late CT coregistered with PET was available to determine final infarct topography. By means of a voxel-based analysis of the PET data, we determined putative thresholds for irreversible tissue damage as the lower limit of the 95% confidence interval calculated from all voxels within the ultimately non-infarcted brain parenchyma ipsilateral to the insult. The following values were found: 8.43 ml/100 ml/min, 0.87 ml/100 ml/min, 1.64 ml/100 ml, 0.27 and 2.21/min, for cerebral blood flow (CBF), oxygen consumption (CMRO2), blood volume (CBV), oxygen extraction fraction and the ratio CBF : CBV, respectively. Voxels below these thresholds occurred significantly more frequently in the final infarct region than in the non-infarcted parenchyma for CBF and CMRO2 (P = 0.016 and P = 0.0045, respectively, Wilcoxon test), but not for the other PET variables. Furthermore, with both CBF and CMRO2, the percentage of irreversible tissue damage voxels in the affected hemisphere relative to the opposite hemisphere was significantly positively correlated to both the volume of final infarct and the neurological outcome at 2 months (all P < 0.005, Spearman ranked test). These findings validate our voxel-based CBF and CMRO2 thresholds for probabilistic mapping of irreversible tissue damage within the 5-18 h interval after stroke onset; however, whether they would be applicable to earlier intervals remains to be determined. Transfer of our procedure for determination of irreversible tissue damage thresholds to other imaging modalities such as single proton emission computed tomography and diffusion-weighted MRI should be straightforward.

Aged↗
PubMed1999

Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer's disease.

Temporoparietal glucose hypometabolism, neuronal loss in the basal forebrain cholinergic structures and preferential accumulation of neurofibrillary tangles in the rhinal cortex (i.e. in the entorhinal and perirhinal cortices) are three early characteristics of Alzheimer's disease. Based on studies of the effects of neurotoxic lesions in baboons, we previously concluded that damage to the cholinergic structures plays, at best, a marginal role in the association neocortex hypometabolism of Alzheimer's disease. In the present study, we have assessed the remote metabolic effects of bilateral neurotoxic lesions of both entorhinal and perirhinal cortices. Using coronal PET coregistered with MRI, the cerebral metabolic rate for glucose (CMR(glc)) was measured before surgery and sequentially for 2-3 months afterward (around days 30, 45 and 80). Compared with sham-operated baboons, the lesioned animals showed a significant and long-lasting CMR(glc) decline in a small set of brain regions, especially in the inferior parietal, posterior temporal, posterior cingulate and associative occipital cortices, as well as in the posterior hippocampal region, all of which also exhibit glucose hypometabolism in Alzheimer's disease. Remarkably, the degree of CMR(glc) decline in four of these regions significantly correlated with the severity of histologically determined damage in the rhinal cortex, strongly supporting the specificity of the observed metabolic effects. There were also differences between the metabolic pattern observed in the lesioned animals and that classically reported in Alzheimer's disease; for instance, the hypometabolism we found in the stratum has not been reported in early Alzheimer's disease, although this structure can be affected in late stages of the disease and has direct anatomical connections with the rhinal cortex. Nevertheless, this study shows for the first time that the temporoparietal and hippocampal hypometabolism found in Alzheimer's disease may partly result from neuroanatomical disconnection with the rhinal cortex. This, in turn, further strengthens the hypothesis that neuronal damage and dysfunction in the rhinal cortices play a major role in the expression of Alzheimer's disease.

Alzheimer Disease↗
PubMed1999

Early postischemic hyperperfusion: pathophysiologic insights from positron emission tomography.

Early postischemic hyperperfusion (EPIH) has long been documented in animal stroke models and is the hallmark of efficient recanalization of the occluded artery with subsequent reperfusion of the tissue (although occasionally it may be seen in areas bordering the hypoperfused area during arterial occlusion). In experimental stroke, early reperfusion has been reported to both prevent infarct growth and aggravate edema formation and hemorrhage, depending on the severity and duration of prior ischemia and the efficiency of reperfusion, whereas neuronal damage with or without enlarged infarction also may result from reperfusion (so-called "reperfusion injury"). In humans, focal hyperperfusion in the subacute stage (i.e., more than 48 hours after onset) has been associated with tissue necrosis in most instances, but regarding the acute stage, its occurrence, its relations with tissue metabolism and viability, and its clinical prognostic value were poorly understood before the advent of positron emission tomography (PET), in part because of methodologic issues. By measuring both CBF and metabolism, PET is an ideal imaging modality to study the pathophysiologic mechanism of EPIH. Although only a few PET studies have been performed in the acute stage that have systematically assessed tissue and clinical outcome in relation to EPIH, they have provided important insights. In one study, about one third of the patients with first-ever middle cerebral artery (MCA) territory stroke studied within 5 to 18 hours after symptom onset exhibited EPIH. In most cases, EPIH affected large parts of the cortical MCA territory in a patchy fashion, together with abnormal vasodilation (increased cerebral blood volume), "luxury perfusion" (decreased oxygen extraction fraction), and mildly increased CMRO2, which was interpreted as postischemic rebound of cellular metabolism in structurally preserved tissue. In that study, the spontaneous outcome of the tissue exhibiting EPIH was good, with late structural imaging not showing infarction. This observation was supported by another PET study, which showed, in a few patients, that previously hypoperfused tissue that later exhibited hyperperfusion after thrombolysis did not undergo frank infarction at follow-up. In both studies, clinical outcome was excellent in all patients showing EPIH except one, but in this case the hyperperfused area coexisted with an extensive area of severe hypoperfusion and hypometabolism. These findings from human studies therefore suggest that EPIH is not detrimental for the tissue, which contradicts the experimental concept of "reperfusion injury" but is consistent with the apparent clinical benefit from thrombolysis. However, PET studies performed in the cat have shown that although hyperperfusion was associated with prolonged survival and lack of histologic infarction when following brief (30-minute) MCA occlusion, it often was associated with poor outcome and extensive infarction when associated with longer (60-minute) MCA occlusion. It is unclear whether this discrepancy with human studies reflects a shorter window for tissue survival after stroke in cats, points to the cat being more prone to reperfusion injury, or indicates that EPIH tends not to develop in humans after severe or prolonged ischemia because of a greater tendency for the no-reflow phenomenon, for example. Nevertheless, the fact that the degree of hyperperfusion in these cat studies was related to the severity of prior flow reduction suggests that hyperperfusion is not detrimental per se. Preliminary observations in temporary MCA occlusion in baboons suggest that hyperperfusion developing even after 6 hours of occlusion is mainly cortical and associated with no frank infarction, as in humans. Overall, therefore, PET studies in both humans and the experimental animal, including the baboon, suggest that hyperperfusion is not a key factor in the development of tissue infarction and that it may be a harmless phenomenon

Acute Disease↗
PubMed1999

Episodic memory in transient global amnesia: encoding, storage, or retrieval deficit?

OBJECTIVES: To assess episodic memory (especially anterograde amnesia) during the acute phase of transient global amnesia to differentiate an encoding, a storage, or a retrieval deficit. METHODS: In three patients, whose amnestic episode fulfilled all current criteria for transient global amnesia, a neuropsychological protocol was administered which included a word learning task derived from the Grober and Buschke's procedure. RESULTS: In one patient, the results suggested an encoding deficit, and in two others, a storage deficit. CONCLUSIONS: The encoding/storage impairment concerning anterograde amnesia documented in our patients stands in clear contrast with the impairment in retrieval which must underly the retrograde amnesia that also characterises transient global amnesia. This dissociation in turn favours the idea of a functional independence among the cognitive mechanisms that subserve episodic memory.

Aged↗
PubMed1999

[The pathophysiology of acute cerebral ischemia: clinical approach using physiologic imaging].

Physiologic imaging has recently allowed major new insights into the pathophysiology of acute ischemic stroke in man. The main observation concerns the major heterogeneity in pathophysiological patterns, with three situations being encountered: 1) cortical ischemic penumbra persisting up till 16 hrs post onset, which would represent an ideal therapeutic target; 2) early spontaneous reperfusion, predictive of favourable clinical and tissular outcome, and a priori requiring no specific therapy; and 3) early extensive necrosis, predictive of malignant hemispheric infarction. Physiologic imaging should soon become a fundamental tool in the evaluation of the individual pathophysiologic situation before a therapeutic decision about entry into trials is made.

Humans↗
PubMed1999

Parametric PET imaging of 5HT2A receptor distribution with 18F-setoperone in the normal human neocortex.

UNLABELLED: Because of 5HT2A receptor's (5HT2AR) putative role in several neuropsychiatric diseases, studying it in vivo is an important goal. 18F-setoperone is a well-validated and widely used PET radioligand for the study of neocortical 5HT2AR. We have previously developed and validated in baboons a method to generate parametric maps of the binding potential (i.e., the k3-to-k4 ratio) on a pixel-by-pixel basis, based on a single-dose tracer amount dynamic 18F-setoperone PET paradigm, and with the receptor-poor cerebellum as reference structure. However, previous semiquantitative PET human studies suggested that nonspecific (NS) binding in the neocortex might not be identical to that in the cerebellum. METHODS: As a first step in the development of k3:k4 parametric mapping in humans, we therefore estimated directly the NS binding of 18F-setoperone in the neocortex of four young healthy volunteers who were studied with PET both before and after 2 wk of daily therapeutic oral doses of sertindole, an atypical neuroleptic possessing strong 5HT2AR antagonistic activity. RESULTS: Visual analysis of the dynamic PET data obtained over 120 min confirmed that virtually full receptor saturation had indeed been achieved; however, the late neocortical time-activity curves (TACs) progressively fell to lower uptake values than corresponding cerebellar TACs and could not be fitted according to a four-compartment (four-Cpt) nonlinear model, indicating lack of specific binding. The cerebellum TACs for both the control and the challenge conditions, as well as the challenge neocortical TACs, were fitted according to three-Cpt modeling, providing the k/k6 ratio and in turn the f2 fraction for both structures. Despite the small sample of only four subjects, the f2 fraction for the neocortex was significantly larger (i.e., NS binding was smaller) than that estimated for the cerebellum. This allowed us to determine the k3-to-k4 ratio for the control neocortex using the challenge neocortex as reference structure, that is, without using the cerebellum at all. This "assumption-free" approach was also successfully used to generate k3:k4 maps for these four subjects, which showed highest values for the temporal cortex. CONCLUSION: This study shows that, for every new PET or SPECT radioligand and when estimation of specific binding is based on a reference structure, it is important to determine the uniformity of nonspecific binding before proceeding with human investigations.

Adult↗
PubMed1998

Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping.

The aging process is thought to result in changes in synaptic activity reflecting both functional and structural cell derangement. However, previous PET reports on age-related changes in resting brain glucose utilization (CMRglc) have been discrepant, presumably because of methodological as well as subject screening differences. In contrast to other studies, which used a region of interest approach, the objective of the present work was to determine, by means of the SPM software, the changes in regional CMRglc as a function of age in 24 optimally healthy, unmedicated volunteers of ages from 20 to 67 years. Global CMRglc showed a significant decline with age (approximately 6% per decade, P < 0.05), which concerned all the voxels studied save for most of the occipital cortex and part of the cerebellum. The most significant effects (P < 0.001) concerned the association neocortex in perisylvian temporoparietal and anterior temporal areas, the insula, the inferior and posterior-lateral frontal regions, the anterior cingulate cortex, the head of caudate nucleus, and the anterior thalamus, in a bilateral and essentially symmetrical fashion. The high posterior parietal cortex was not sampled in this study. This distribution of changes in CMRglc with age may differ from that seen in Alzheimer' disease, where the earliest metabolic reduction has been shown to affect the posterior cingulate cortex.

Adult↗
PubMed1998

Effect of environmental sound familiarity on dynamic neural activation/inhibition patterns: an ERD mapping study.

The aim of this study was to analyze the timing and topography of brain activity in relation to the cognitive processing of different types of auditory information. We specifically investigated the effects of familiarity on environmental sound identification, an issue which has been little studied with respect to cognitive processes, neural substrates, and time course of brain activity. To address this issue, we implemented and applied an electroencephalographic mapping method named event-related desynchronization, which allows one to assess the dynamics of neuronal activity with high temporal resolution (here, 125 ms); we used 19 recording electrodes with standard positioning. We designed an activation paradigm in which healthy subjects were asked to discriminate binaurally heard sounds belonging to one of two distinct categories, "familiar" (i.e., natural environmental sounds) or "unfamiliar" (i.e., altered environmental sounds). The sounds were selected according to strict preexperimental tests so that the former should engage greater semantic, and the latter greater structural, analysis, which we predicted to preferentially implicate left posterior and right brain regions, respectively. During the stimulations, significant desynchronizations (thought to reflect neuronal activations) were recorded over left hemisphere regions for familiar sounds and right temporofrontal regions for unfamiliar sounds, but with only few significant differences between the two sound categories and a common bilateral activation in the frontal regions. However, strongly significant differences between familiar and unfamiliar sounds occurred near the end of and following the stimulations, due to synchronizations (though to reflect deactivations) which appeared over the left posterior regions, as well as the vertex and bilateral frontal cortex, only after unfamiliar sounds. These unexpected synchronizations after the unfamiliar stimuli may reflect an awareness of the unfamiliarity of such sounds, which may have induced an inhibition of semantic and episodic representations because the latter could not be associated with meaningless sounds.

Arousal↗
PubMed1998

The functional neuroanatomy of episodic memory: the role of the frontal lobes, the hippocampal formation, and other areas.

Because it allows direct mapping of synaptic activity during behavior in the normal subject, functional neuroimaging with the activation paradigm, especially positron emission tomography, has recently provided insight into our understanding of the functional neuroanatomy of episodic memory over and above established knowledge from lesional neuropsychology. The most striking application relates to the ability to distinguish the structures implicated in the encoding and the retrieval of episodic information, as these processes are extremely difficult to differentiate with behavioral tasks, either in healthy subjects or in brain-damaged patients. Regarding encoding and retrieval, the results from most studies converge on the involvement of the prefrontal cortex in these processes, with a hemispheric encoding/retrieval asymmetry (HERA) such that the left side is preferentially involved in encoding, and the right in retrieval. However, there are still some questions, for instance, about bilateral activation during retrieval and a possible specialization within the prefrontal cortex. More expected from human and monkey lesional data, the hippocampal formation appears to play a role in both the encoding and the retrieval of episodic information, but the exact conditions which determine hippocampal activation and its fine-grained functional neuroanatomy have yet to be fully elucidated. Other structures are activated during episodic memory tasks, with asymmetric activation that fits the HERA model, such as preferentially left-sided activation of the association temporal and posterior cingulate areas in encoding tasks and preferentially right-sided activation of the association parietal cortex, cerebellum, and posterior cingulate in retrieval tasks. However, this hemispheric asymmetry appears to depend to some extent on the material used. These new data enhance our capacity to comprehend episodic memory deficits in neuropsychology, as well as the neural mechanisms underlying the age-related changes in episodic memory performances.

Brain Mapping↗
PubMed1998

[11C]S21007, a putative partial agonist for 5-HT3 receptors PET studies. Rat and primate in vivo biological evaluation.

We recently labeled with carbon-11, a high affinity, selective, 5-HT3 receptor (5-HT3R) ligand, S21007, for potential positron emission tomography (PET) applications. To evaluate the in vivo binding properties of [11C]S21007, its brain regional distribution, tissue and plasma pharmacokinetics and plasma metabolisation were characterized. To circumvent the problem of highly discrete brain localization of the 5-HT3R (area postrema, hippocampus), we designed an original approach combining high-resolution imaging techniques (ex vivo phosphor plate autoradiography and MRI-guided coronal PET in the rat and baboon, respectively). After i.v. injection of trace amounts of [11C]S21007 to rats, phosphorimager autoradiography failed to reveal in vivo specific binding to, nor selectivity for 5-HT3R-rich areas. PET studies in the baboon showed consistent results, i.e., there was no selective accumulation of [11C]S21007 in the area postrema or hippocampus, and neither displacement nor presaturation with cold S21007 resulted in significant changes in tissue distribution or kinetics of [11C]S21007.

Animals↗
PubMed1998

Synthesis and biological investigations of [18F]MR18445, a 5-HT3 receptor partial agonist.

18F Labelled MR18445 (4-[4-(4-[18F]fluorobenzyl)piperazino]-7-methoxypyrrolo++ +[1,2-alpha] quinoxaline), a selective 5-HT3 receptor partial agonist with nanomolar affinity, was synthesized and examined as a potential radioligand for PET imaging of brain 5HT3 receptors. Radiotracer was prepared by N-alkylation of the MR18491 precursor with 4-[18F]fluorobenzyl iodide. This latter was synthesized in a three-step procedure from 4-[18F]fluorobenzaldehyde obtained by 18F-nucleophilic displacement of 4-nitrobenzaldehyde, subsequently reduced to 4-[18F]fluorobenzyl alcohol and converted into reactive 4-[18F]fluorobenzyl iodide. The reduction step was performed on a column filled with NaBH4/Al2O3 and 4-[18F]fluorobenzyl alcohol was obtained with high reproducible yield (82-93% from 4-[18F]fluorobenzaldehyde) if there were traces of water in the system. The radiosynthesis of [18F]MR18445 required approximately 120 min. Semi-preparative HPLC purification followed by formulation gave injectable solutions of [18F]MR18445 with a radiochemical purity > 99%. The overall yield of the synthesis was mainly dependent upon the first step efficiency of aromatic incorporation of 18F- and varied from 12% to 29%. All the synthetic procedure was realized on a ZYMARK robotic system. Biological in vivo studies in rats showed that uptake of [18F]MR18445 in brain was rapid and high. No evidence of radiolabeled metabolites could be observed in the brain as late as 40 min after injection, despite the rapid appearance of metabolites in the plasma. However, neither phosphorimaging autoradiographic studies in rats nor PET experiments in baboons revealed specific binding of the radiotracer in brain, suggesting [18F]MR18445 is not suitable for 5-HT3 receptors PET studies.

Animals↗
PubMed1998

The neural substrates of memory systems impairment in Alzheimer's disease. A PET study of resting brain glucose utilization.

The aim of this study was to determine the neuronal basis for memory impairment in Alzheimer's disease by taking advantage of the clinical and metabolic heterogeneity of this pathology. To this end, 19 patients satisfying the NINCDSADRDA criteria for probably Alzheimer's disease of mild-to-moderate severity underwent a detailed examination of the five memory systems according to Tulving's model, together with a PET measurement of resting regional cerebral glucose utilization (CMRGlc). Compared with controls, the patients as a group showed the expected memory and metabolic profiles of impairment. Correlations (corrected for the effects of ageing) were calculated between memory scores and CMRGlc (normalized by the vermis CMRGlc) using two methods: (i) the classic regions-of-interest method, based on a priori hypotheses and individual coregistered structural MRI; and (ii) the statistical parametric mapping method which allows a systematic voxel-by-voxel analysis, in a more descriptive and exploratory way. Significant correlations were above chance levels and largely consistent between the two methods. They were almost exclusively positive (i.e. in the neurobiologically expected direction) and their distribution showed striking differences according to each memory system. Thus, verbal episodic memory impairment was related to changes in a large neuronal network including not only the limbic structures (mesial temporal cortex, thalamus and cingulate gyrus, with left side predominance) but also the parietotemporal and frontal association cortices of the right hemisphere, possibly on a compensatory basis. Regardless of modality, short-term memory tests were mainly correlated with bilateral activity in posterior association cortex, and also with activity in left prefrontal cortex for the visuospatial span, possibly indicating essentially uniform strategies for the performance of the different tasks. As predicted, semantic memory scores correlated with activity in temporoparietal and frontal association cortices of the left hemisphere, and also with activity in left cingulate cortex. Thus, for episodic, short-term and semantic memory, many findings fit classical neuropsychology, while most of the less expected ones were consistent with recent results from functional neuro-imaging in healthy subjects, notably with the hemispheric encoding/ retrieval asymmetry (HERA) model; only few findings suggested possible reorganization processes and/or recourse to unexpected cognitive strategy. Finally, only negative correlations were found for perceptual priming and procedural memory; although they could arise by chance, some of these unexpected findings give rise to interesting hypotheses about the cognitive relationships between the most and least affected memory systems. This study documents the validity and usefulness of our approach in unravelling the neural substrates of cognitive impairment in brain pathology without focal tissue loss such as that seen in neurodegenerative diseases.

Aged↗
PubMed1998

Evaluation of the ratio of cerebral blood flow to cerebral blood volume as an index of local cerebral perfusion pressure.

Local cerebral perfusion pressure (CPP), a crucial parameter that should allow a better assessment of the haemodynamic compromise in cerebrovascular diseases, is not currently measurable by non-invasive means. Experimental and clinical studies have suggested that the regional ratio of cerebral blood flow to cerebral blood volume (CBF:CBV), as measured by PET, represents an index of local CPP in focal ischaemia. The present study was designed to evaluate further the reliability of the CBF:CBV ratio during manipulations of CPP by deliberately varying mean arterial pressure (MAP) in the anaesthetized baboon. Cortical CBF, CBV, cerebral metabolic rate for oxygen (CMRO2) and oxygen extraction fraction were measured by PET using the (15)O steady-state technique in 10 anaesthetized baboons. Five baboons (Group A) underwent four PET examinations at different levels of MAP: base line (101 +/- 6 mmHg) followed by moderate hypotension (58 +/- 3 mmHg) and, in a separate experiment, minor hypotension (72 +/- 3 mmHg) followed by profound hypotension (34 +/- 5 mmHg). Trimetaphan was used to lower MAP to minor and moderate levels while profound hypotension was achieved by the combined effects of trimetaphan and lower-body negative pressure. Five other baboons (Group B) were subjected to hypertension (121 +/- 2 mmHg) induced by metaraminol and were compared with their base line state (81 +/- 10 mmHg). While CBF displayed significant changes with varying MAP, i.e. decrease and increase with hypotension and hypertension, respectively (-11% from base line to moderate hypotension compared with -20%, from minor to profound hypotension and +31% from base line to hypertension), CBV was more variable and did not significantly change, except with profound hypotension when the increase was significant (+13%). The CBF:CBV ratio decreased significantly at all stages of hypotension (-21 and -31%) and was significantly increased during hypertension (+30%). Importantly, the CBF:CBV ratio demonstrated a significant correlation with MAP (rho = 0.78, Spearman's rank correlation coefficient, P < 0.01). No major changes in CMRO2 were noted during either hypotension or hypertension. Our results demonstrate that, under physiological conditions, cortical CBF:CBV is significantly correlated with CPP, itself a function of MAP. In the investigated range of MAP, the relationships between CBF:CBV and MAP appear to be linear. These findings further argue for the reliability of CBF:CBV as an index of CPP in situations where increases or decreases of MAP without superimposed changes in cerebrovascular tone are encountered, and they confirm the potential usefulness of this regional ratio for clinical investigations and management in cerebrovascular diseases.

Animals↗
PubMed1998

Effects of damage to the basal forebrain on brain glucose utilization: a reevaluation using positron emission tomography in baboons with extensive unilateral excitotoxic lesion.

Neuronal loss in the basal forebrain cholinergic structures and frontotemporal hypometabolism are two characteristics of Alzheimer's disease, but their interrelations still are unsettled. We previously reported that unilateral electrolytic lesions of the nucleus basalis of Meynert in baboons were associated with marked but transient cortical hypometabolism. The current study reevaluates this issue using improved methodology. Baboons with unilateral ibotenic acid lesion of all three basal forebrain cholinergic structures (IBO group) were compared with sham-operated animals. The CMRglc was measured with high-resolution coronal positron emission tomography scanning coregistered with magnetic resonance imaging, before surgery and serially between 4 and 72 days afterward. Severe histologic basal forebrain damage and a decrease of more than 50% in cortical choline acetyltransferase activity were found postmortem in the IBO group. Transient and nonspecific hypometabolism was found in the needle track area in both groups. Compared with the sham-operated group, only marginally significant decreases in ipsilateral-contralateral CMRglc ratios were observed in the IBO group, affecting only 1 of 14 neocortical areas investigated (the anterior temporal cortex) at a single postsurgical time (day 14), and the posterior hippocampal region at days 14 and 38. Furthermore, there was no consistently significant correlation between ipsilateral-contralateral CMRglc ratios and cortical choline acetyltransferase activity values in any of the four regions analyzed. These results suggest that cholinergic deafferentation play at best a marginal role in the brain hypometabolism observed in Alzheimer's disease.

Alzheimer Disease↗