Biomedical subjects

M Reivich

Publications and source records attributed to M Reivich.

At least 19 recordsLinked to original sources

PubMed2001

Progressive peripheral agraphia.

We describe RW, a patient who presented with writing difficulty that deteriorated over time. While her graphemes were typically legible, her writing was extremely slow, and her letters were written in an inconsistent and heterogeneous manner (e.g. each "a" in the word "banana" was produced in a different way). Her mental imagery of letters was impoverished, and she also produced allographic errors in her writing. She had some spelling errors as well, but many of these were due to omissions, perseverations, and motor operations. A positron emission tomography scan demonstrated superior parietal occipital and superior frontal defects that were more evident on the left than the right. Our observations are consistent with the hypothesis that RW has a deficit retrieving physical letter forms as manifested by her heterogeneous and slow production of letter forms. This disruption of grapheme retrieval is associated with interruption of a superior frontal-parietal system in the left hemisphere.

Aged↗

PubMed2001

Interactions between the endothelium-derived relaxing factor/nitric oxide system and the endogenous opiate system in the modulation of cerebral and spinal vascular CO2 responsiveness.

The role of the L-arginine-nitric oxide (NO) system, the role of the endogenous morphine-like substances (endorphins), and the possible interaction between these two systems in the modulation of regional cerebral and spinal CO2 responsiveness was investigated in anesthetized, ventilated, normotensive, normoxic cats. Regional cerebral blood flow was measured with radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions in nine individual cerebral and spinal cord regions. General opiate receptor blockade by 1 mg/kg naloxone intravenously alone or NO synthase blockade by 3 mg/kg N(omega)-nitro-L-arginine-methyl ester (L-NAME) intravenously alone caused no changes in regional CO2 responsiveness. Combined administration of these two blocking agents in the very same doses, however, resulted in a strong potentiation, with a statistically significant reduction of the CO2 responsiveness observed. Separation of the blood flow response to hypercapnia and hypocapnia indicates that this reduction occurs only during hypercapnia. Specific mu and delta opiate receptors were blocked by 0.5 mg kg(-1) IV beta-funaltrexamine and 0.4 mg kg(-1) IV naltrindole, respectively. The role of specific mu and delta opiate receptors in the NO-opiate interaction was found to be negligible because neither mu nor delta receptor blockade along with simultaneous NO blockade were able to decrease CO2 responsiveness. The current findings suggest a previously unknown interaction between the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) system and the endogenous opiate system in the cerebrovascular bed during hypercapnic stimulation, with the phenomenon not mediated by mu or delta opiate receptors.

Animals↗

PubMed2001

A new model of localized ischemia in rat somatosensory cortex produced by cortical compression.

BACKGROUND AND PURPOSE: Because of its precise connectivity and functional specificity, the rat whisker-barrel system offers an excellent opportunity to study experience-dependent neuroplasticity. However, data are lacking regarding the neuroplasticity of this system after cerebral ischemia. The purpose of the present study was to develop a reproducible model for the production of ischemia/reperfusion of the posteromedial barrel subfield (PMBSF) in the rat, which is the visible representation of the large whiskers on the opposite face. METHODS: Focal cortical ischemia was induced in male Sprague-Dawley rats (n=40) by slowly compressing the intact dura (maximum 0.05 mm/s) with a 4- or 5-mm-diameter brass cylinder equipped with a laser-Doppler probe, combined with ipsilateral common carotid artery occlusion. The microvascular blood flow of PMBSF during compression ischemia was maintained at 18% to 20% of baseline flow for 1 hour. The total infarction volume was measured by 2,3,5-triphenyltetrazolium chloride staining at several reperfusion times, and pathological examination was performed on hematoxylin-eosin-stained sections. RESULTS: The infarct volumes were 36.5+/-9.2 (n=9), 40.7+/-7.7 (n=7), and 36.6+/-6.4 mm(3) (n=5) at 24 hours, 72 hours, and 7 days after ischemia, respectively, with no significant differences among these values. There was no evidence of damage to white matter or to deep gray matter and no evidence of hemorrhage. The topographic distribution of the damaged tissue was in good agreement with that of PMBSF. CONCLUSIONS: This stroke model produces a highly consistent cortical infarct in PMBSF and can facilitate the study of behavioral, functional, and structural consequences after cerebral ischemia/reperfusion in the rat somatosensory cortex.

Animals↗

PubMed1999

Hippocampal cell density and subcortical metabolism in temporal lobe epilepsy.

PURPOSE: Correlations between hippocampal cell density and subcortical metabolism in patients with temporal lobe epilepsy (TLE) were studied to explore possible links between subcortical function and the regulation of hippocampal excitability. METHODS: Resected hippocampal cell densities were correlated with cortical and subcortical regional cerebral metabolic rate for glucose (CMRglu), as measured by [18F]-fluorodeoxyglucose positron emission tomography (18-FDG-PET), in 39 patients with intractable TLE who underwent anterior temporal lobectomy (ATL). CMRglu was measured ipsilateral and contralateral to the resected temporal lobe. Linear regression techniques were used for statistical analysis. RESULTS: Hilar cell densities correlated positively and significantly with CMRglu in the bilateral thalamus, putamen and globus pallidus, and the ipsilateral caudate. Dentate granule cell densities correlated positively and significantly with CMRglu in the bilateral thalamus and putamen. There was no significant correlation between cell densities and CMRglu in any cortical region, including the hippocampus. CONCLUSIONS: We postulate that hippocampal cell loss results in decreased efferent synaptic activity to the thalamus and basal ganglia, causing decreased neuronal activity in these structures with consequent hypometabolism. This synaptic activity has a significant bilateral component. Subcortical hypometabolism in patients with TLE may reinforce the epileptogenic potential of mesial temporal lobe discharges.

Amygdala↗

PubMed1999

Limbic activation during cue-induced cocaine craving.

OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the non-drug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.

Adult↗

PubMed1998

Cognitive, neuroimaging, and pathological studies in a patient with Pick's disease.

We conducted cognitive, imaging, and neuropathological studies on a patient with Pick's disease. The patient was impaired at interpreting sentences with complex grammatical constructions, differing significantly from control subjects and patients with Alzheimer's disease (AD). Evaluation of regional brain functioning at rest, with positron emission tomography, revealed reduced left frontal activity compared with control subjects and AD patients. Autopsy demonstrated the classic pathology of Pick's disease, including massive neuron loss and gliosis in the frontal and cingulate cortex as well as numerous tau-positive hippocampal Pick bodies. The abnormal tau proteins were phosphorylated at the same amino acid residues as AD paired helical filament tau (PHFtau), but they exhibited a unique migration profile on western blot. Our observations support the hypothesis that a distinct variety of hyperphosphorylated tau in Pick's disease compromises the long-term viability of selectively vulnerable populations of neurons in frontal cortices that contribute to sentence processing.

Aged↗

PubMed1998

Estimation of component and parameter distributions in spectral analysis.

A method is presented for estimating the distributions of the components and parameters determined with spectral analysis when it is applied to a single data set. The method uses bootstrap resampling to simulate the effect of noise on the computed spectrum and to correct for possible bias in the estimates. A number of bootstrap procedures are reviewed, and one is selected for application to the kinetic analysis of positron emission tomography dynamic studies. The technique is shown to require minimal assumptions about noise in the measurements, and its small sample properties are established through Monte-Carlo simulations. The advantages and limitations of spectral analysis with bootstrap resampling for deriving inferences for tracer kinetic modeling are illustrated through sample analyses of time-activity curves for [18F]fluorodeoxyglucose and [15O]-labeled water.

Algorithms↗

PubMed1997

Fluorine-18-FDG evaluation of crossed cerebellar diaschisis in head injury.

UNLABELLED: This study investigates the phenomenon of crossed cerebellar diaschisis in head injury patients. METHODS: We visually compared fluorine-18-fluorodeoxyglucose (FDG)-PET images to radiograph computed tomography or magnetic resonance images in 19 patients with head injury. RESULTS: We found that of 68 focal unilateral lesions, 40% were associated with contralateral cerebellar hypometabolism and 19% were associated with ipsilateral cerebellar hypometabolism. Of supratentorial, extraparenchymal lesions (n = 20), 45% were associated with contralateral cerebellar hypometabolism, whereas 15% had ipsilateral cerebellar hypometabolism. Intraparenchymal lesions were associated with contralateral cerebellar hypometabolism in 38% of the patients and with ipsilateral cerebellar hypometabolism in 21% of the patients. Of the cortical lesions that were the patients' most severe injury, 69% were associated with contralateral cerebellar hypometabolism, whereas only 8% were associated with ipsilateral cerebellar hypometabolism. In patients with focal supratentorial lesions alone, 50% of all focal lesions were associated with contralateral cerebellar hypometabolism and 13% had ipsilateral hypometabolism. Of patients with both focal and diffuse brain injuries, 27% of the focal lesions had contralateral cerebellar hypometabolism and 27% had ipsilateral cerebellar hypometabolism to the most severe focal injury. CONCLUSION: Crossed cerebellar diaschisis is seen more often in patients with focal cortical or extraparenchymal injuries and is not seen in patients with multiple or diffuse brain injuries. Furthermore, this predominance is more pronounced with lesions of the greatest severity.

Adult↗

PubMed1996

Radiosynthesis and biodistribution of the S-[18F]fluoroethyl analog of McN5652.

[11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[18F]fluoroethyl analog of McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([18F]fluoroethylthio)-phenyl] pyrrolo-[2,1-a]-isoquinoline) ([18F]FEMcN) and evaluated as a PET radiotracer for imaging serotonin uptake sites. The radiosynthesis was performed via a one-pot, two-step procedure. In the first step, 1-bromo-2-[18F]fluoroethane was prepared from 2-bromoethyl triflate and K18F/Kryptofix 2.2.2. in THF at room temperature. The second step, the S-fluoroalkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2-[18F]fluoroethane, by adding the normethyl McN5652 to the reaction vial, which was warmed at 45 degrees C for 1 min. The fluoroalkylation reaction proceeded quickly, giving [18F]FEMcN in an average overall radio-chemical yield of 13 +/- 7%. The specific activity was 1593 +/- 625 mCi/mumol. Ex vivo autoradiographic studies revealed that [18F]FEMcN accumulated into regions with high densities of 5-HT uptake sites such as hypothalamus, substantia nigra, and raphe nuclei. With blockade by nitroquipazine, a selective and highly potent 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, suggesting that this radiotracer binds specifically to 5-HT uptake sites. The regional distribution of [18F]FEMcN at 60 min postinjection correlated with the distribution of [11C]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT uptake blocker agreed with the distribution of the number of 5-HT uptake sites measured in vitro. Thus, 5-HT uptake sites were visualized in vivo with [18F]FEMcN. However, comparison with the in vivo behavior of [11C]McN5652 indicated less favorable properties of [18F]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood-brain barrier penetration and lower target-to-nontarget ratios.

Animals↗

PubMed1996

Use of positron emission tomography and evoked potentials in the detection of cortical afferents from the gastrointestinal tract.

OBJECTIVE: Positron emission tomography permits precision identification of the cerebral regions involved in physiologic functions. As the cerebral localization for visceral sensation has not been identified, our aim was to examine the cerebral viscerotopic representation for rectal sensation. METHODS: Cerebral-evoked potentials were measured in five healthy volunteers who underwent rectal balloon distension. Simultaneously, cerebral blood flow was measured using positron emission tomography with 15H2O. RESULTS: A cerebral-evoked potential occurred with rectal balloon distension. An increase in cerebral blood flow was noted in the pre- and postcentral gyrus and the thalamus. CONCLUSION: The techniques for measuring cerebral-evoked potentials and cortical blood flow are useful in the delineation of the cerebral regions subserving visceral sensation.

Brain↗

PubMed1996

Regional heterogeneity and differential vulnerability of cerebral and spinal vascular CO2-responsiveness during graded haemorrhagic hypotension.

Regional inhomogeneity of cerebrovascular CO2-sensitivity as well as its changes at three different levels of standardized haemorrhagic hypotension were studied in ten distinct brain and spinal cord regions of anesthetized, ventilated cats. Regional cerebral blood flow was measured with radiolabelled microspheres in hypocapnic, normocapnic, and hypercapnic conditions, and CO2-responsiveness was determined from the equation of the slopes of the best fit regression lines to the obtained flow values. It was concluded that in normotensive, normoxic cats response of the cerebral and spinal vessels to PaCO2 alterations can be assigned to four major categories. The CO2-responsiveness of a brain region is not solely determined by the rate of its basal steady state blood flow: CO2-reactivity of the hypothalamus was significantly different from that of any other investigated regions with almost identical steady state flow values. Vulnerability of the cerebrovascular CO2-sensitivity during hypotension was different from region to region, with the vessels of the pons-medulla oblongata region being the most sensitive to haemorrhage. Reduced regional cerebral and spinal CO2-responsiveness during haemorrhage is not a consequence of a reduced L-arginine supply for nitric oxide generation since administration of an excess amount of the precursor L-arginine failed to restore the haemorrhage-induced reduction of regional CO2-sensitivity at the 60 mm Hg mean arterial pressure level.

Animals↗

PubMed1995

Resting cerebral glucose metabolism in first-episode and previously treated patients with schizophrenia relates to clinical features.

BACKGROUND: Functional neuroimaging can elucidate brain dysfunction in schizophrenia. The frontal, temporolimbic, and diencephalic regions have been implicated. There is a lack of prospective samples of first-episode and previously treated patients followed up longitudinally. METHODS: Patients and controls (42 per group) were studied. Positron emission tomography with flurodeoxyglucose, cross-registered with magnetic resonance imaging, measured metabolism. Scales assessed clinical features, premorbid adjustment, and outcome. RESULTS: There were no differences between groups in whole-brain metabolism or regional ratios or in anterior-posterior gradients, but left midtemporal metabolism was relatively higher in patients. This was pronounced in the negative and Schneiderian and absent in the paranoid subtypes. Higher metabolism and lower relative left hemispheric values were associated with better premorbid adjustment and outcome. A higher subcortical-cortical gradient was noted in first-episode patients. CONCLUSIONS: There are no resting metabolic abnormalities in any brain region, but abnormal gradients are evident. These vary in subtypes, and laterality is associated with functioning. The results support the hypothesis of temporolimbic disturbance in schizophrenia that is all ready present at the onset of illness.

Adult↗

PubMed1995

PET imaging studies of dopamine D2 receptors: comparison of [18F]N-methylspiperone and the benzamide analogues [18F]MABN and [18F]MBP in baboon brain.

A series of positron emission tomography (PET) imaging studies was conducted in a baboon with the benzamide derivatives [18F]2,3-dimethoxy-N-[9-(4-fluorobenzyl)-9-azabicyclo[3.3.1]non an-3 beta-yl]benzamide ([18F]MABN) and [18F]2,3-dimethoxy-N-[1-(4-fluorobenzyl)piperidin-4-yl]be nza mide ([18F]MBP). Studies were also conducted with the butyrophenone [18F]N-methylspiperone (NMSP) for comparison. Tissue-time activity curves of [18F]MABN are similar to those of [18F]NMSP since both compounds displayed approximately the same uptake in the basal ganglia and displayed irreversible binding kinetics in vivo. However, the rapid rate of clearance from the cerebellum and high basal ganglia:cerebellum ratio of [18F]MABN indicate that this compound has a much lower amount of nonspecific binding than [18F]NMSP. [18F]MBP displayed a higher uptake in the basal ganglia relative to [18F]NMSP and [18F]MABN and exhibited reversible binding kinetics in vivo. This property of [18F]MBP is desirable since the uptake of radioactivity in D2-rich ligands is less likely to be influenced by changes in cerebral blood flow. The current data suggest that both [18F]MABN and [18F]MBP are promising ligands for studying dopamine D2 receptors with PET.

Animals↗

PubMed1995

Failure of levemopamil to improve histological outcome following temporary occlusion of the middle cerebral artery in cats.

Levemopamil, a novel calcium channel blocker with antagonistic action on serotonin S2-receptors has been reported to be a promising compound for therapy in cerebral ischemia. This data has been obtained in the rat only, and it is of interest to determine if these beneficial effects are present in other models of ischemia in other species. The present study was therefore designed to examine its effect on histological outcome and changes in EEG after focal cerebral ischemia and reperfusion in the cat. Focal cerebral ischemia was induced by a reversible 1 hour occlusion of the middle cerebral artery followed by reperfusion of the brain. Six hours after the induction of the insult, the brain was perfusion-fixed and evaluated for histological damage by light microscopy. In 8 animals an intravenous infusion of levemopamil was initiated 5 minutes after middle cerebral artery occlusion at a rate of 4 mg/kg/h for 15 min and then at 0.6 mg/kg/h until the end of the study. A control group (n = 7) received a similar infusion of saline. The EEG amplitude did not differ between the two groups at any point of the study. The area of ischemic damage in the sections obtained for histological examination at 1-mm intervals, as well as the total volume of ischemic damage for both groups (treated: 1.33 cm3; untreated: 0.97 cm3) also did not show any significant differences. These results indicate that postischemic treatment with levemopamil at this dose, and in this model of focal cerebral ischemia and reperfusion, does not attenuate the ischemic damage.

Animals↗

PubMed1995

Effects of central inhibition of nitric oxide synthase on focal cerebral ischemia in rats.

We have investigated whether central inhibition of nitric oxide synthase (NOS) could modify the tissue damage of focal cerebral ischemia produced by occlusion of the middle cerebral artery (MCA) in rats. NG-Nitro-L-arginine methyl ester (L-NAME) was administered intracerebroventricularly at two doses 15 min prior to occlusion of the MCA, as well as 4 and 24 h following occlusion. After the injection of L-NAME, the catalytic activity of the constitutive NOS, considered to be mainly neuronal, was effectively suppressed in the subcortical gray matter bilaterally, but not in the ischemic territory. Seven days after the MCA occlusion, the brains were evaluated for histopathologic damage. High-dose administration of L-NAME (120 micrograms/kg 15 min prior to MCA occlusion, followed by 150 micrograms/kg 4 and 24 h after occlusion) produced an enlargement of the infarct area and increased the volume of ischemic damage. These results indicate that extensive inhibition of NOS by a central route can increase the cerebral infarct size in focal ischemia even if NOS is not inhibited in the ischemic tissue and suggest that NO may also play a potentially beneficial role as well as a neurodestructive role in the pathophysiological mechanisms of focal cerebral ischemia.

Amino Acid Oxidoreductases↗

PubMed1995

Clinicopathological observations in middle cerebral artery occlusion in the cat.

This study was designed to investigate the relationships among neurological deficits, changes in the electroencephalogram (EEG) and morphological damage over a one week period following temporary occlusion (2 h) of the middle cerebral artery (MCA) in the cat. The animals were grouped into mild, moderate, and severe stroke based on the EEG alterations produced 30 min after the MCA occlusion. All three grades of stroke showed a precipitous fall in mean EEG amplitude followed by a recovery during a 4 h recirculation period. Over the subsequent 7 days there was a gradual secondary depression in the EEG amplitude. Post-operatively, a secondary fall in EEG amplitude in the contralateral hemisphere was also noted in all stroke groups corresponding to the clinical phenomenon of 'diaschisis'. The overall neurological score differed significantly among the severe, moderate, and mild stroke groups. The neurological deficits on the 7th day were highly correlated with the degree of morphological damage. Additionally, the reduction of EEG was also well correlated with the pathological data. This stroke model in the cat has provided important data concerning the restitution of brain function following chronic focal ischaemia.

Animals↗

PubMed1995

False lateralization of temporal lobe epilepsy with FDG positron emission tomography.

We report 2 patients in whom visual interpretation of interictal positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) suggested false lateralization of an epileptic focus. PET scans were interpreted as showing diffuse left temporal lobe hypometabolism in 1 patient and lateral temporal hypometabolism in the other. However, seizures began in the right mesial temporal lobe in both patients, and both responded favorably to right temporal lobectomy. In 1 patient, the intracranial EEG showed continuous asymptomatic subclinical seizure activity emanating from the right amygdala. These limbic discharges probably caused unrecognized right temporal lobe hypermetabolism. In the other case, quantitative analysis of metabolic rates showed conflicting mesial and lateral metabolic indexes. Frequent mesial interictal discharges might have increased lateral temporal metabolism. We conclude that asymptomatic epileptiform activity may alter temporal lobe metabolism and that quantitative PET analysis helps clarify contradictory visual PET interpretations.

Adult↗

PubMed1994

Prolonged effects of MK-801 in the cat during focal cerebral ischemia and recovery: survival, EEG activity and histopathology.

Previously we reported an improvement in histological outcome in cats treated with MK-801 shortly after the induction of temporary middle cerebral artery occlusion, and examined after 2 h of ischemia followed by 4 h of reperfusion. This study investigates the prolonged effects of the same drug treatment. Focal cerebral ischemia was produced in 34 cats by temporary occlusion of the left middle cerebral artery for 2 h. Stroke severity was determined using the ratio of the EEG amplitude from the ipsilateral to that of the contralateral hemisphere. Thirty minutes after the onset of ischemia, cats were treated i.v. with either 1 mg/kg MK-801 or saline. Electrocortical activity of the animals who survived were followed for 6 days postocclusion at which point they were sacrificed for histopathological analysis. Twelve of the animals died during recovery, of which 4 were MK-801 treated, and 8 were saline controls. The EEG ratios in the non-surviving animals were more depressed than in the animals that survived, whereas the depression in the EEG amplitude in both the treated and the control surviving animals was equal. Among the survivors no reduction in infarct size with MK-801 treatment was observed. Thus treatment with MK-801 in the middle cerebral artery occlusion model in the cat leads to a significant increase in the rate of survival (P < 0.05), but no prolonged improvement in late histopathology, in contrast with acute histological findings using this model. MK-801 treatment may be shifting the stroke model towards the survival of animals with larger infarcts. Histological recovery during prolonged reperfusion may eliminate the early neuroprotective effects seen with MK-801 treatment.

Analysis of Variance↗