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Biomedical subjects

N M Alpert

Publications and source records attributed to N M Alpert.

At least 55 records · Page 3Linked to original sources
PubMed1998

Mental rotation of objects versus hands: neural mechanisms revealed by positron emission tomography.

Twelve right-handed men participated in two mental rotation tasks as their regional cerebral blood flow (rCBF) was monitored using positron emission tomography. In one task, participants mentally rotated and compared figures composed of angular branching forms; in the other task, participants mentally rotated and compared drawings of human hands. In both cases, rCBF was compared with a baseline condition that used identical stimuli and required the same comparison, but in which rotation was not required. Mental rotation of branching objects engendered activation in the parietal lobe and Area 19. In contrast, mental rotation of hands engendered activation in the precentral gyrus (M1), superior and inferior parietal lobes, primary visual cortex, insula, and frontal Areas 6 and 9. The results suggest that at least two different mechanisms can be used in mental rotation, one mechanism that recruits processes that prepare motor movements and another mechanism that does not.

Adolescent↗
PubMed1998

Robot-aided functional imaging: application to a motor learning study.

The purpose of this study was to examine the neural activity underlying an implicit motor learning task. In particular, our goals were to determine whether initial phases of procedural learning of a motor task involve areas of the brain distinct from those involved in later phases of learning the task, and what changes in neural activity coincide with performance improvement. We describe a novel integration of robotic technology with functional brain imaging and its use in this study of implicit motor learning. A portable robotic device was used to generate forces that disturbed the subjects' arm movements, thereby generating a "virtual mechanical environment" that the subjects learned to manipulate. Positron emission tomography (PET) was used to measure indices of neural activity underlying learning of the motor task. Eight health, right-handed male subjects participated in the study. Results support the hypothesis that different stages of implicit learning (early and late implicit learning) occur in an orderly fashion, and that distinct neural structures may be involved in these different stages. In particular, neuroimaging results indicate that the cortico-striatal loop may play a significant role during early learning, and that the cortico-cerebellar loop may play a significant role during late learning.

Adult↗
PubMed1997

Effects of dobutamine at maximally tolerated dose on myocardial blood flow in humans with ischemic heart disease.

BACKGROUND: This study tests the hypothesis in humans with ischemic heart disease that myocardial blood flow response to dobutamine is linearly correlated with blood flow response to adenosine. METHODS AND RESULTS: PET with [13N]ammonia was used to measure myocardial blood flow at rest and during adenosine and dobutamine at the maximally tolerated dose. Myocardial segments were defined physiologically on the basis of blood flow response to adenosine: normal, > or = 2 mL x min(-1) x g(-1); abnormal, < 2 mL x min(-1) x g(-1); and "steal," decline versus baseline > or = 0.15 mL x min(-1) x g(-1). The patient population consisted of 11 men and 2 women. Dobutamine increased heart rate (79+/-22 to 115+/-28 bpm) and rate-pressure product (9748+/-2862 to 15,157+/-3433 mm Hg/min) significantly (both P<.01). Myocardial blood flow at rest in abnormal segments (0.50+/-0.23 mL x min(-1) x g(-1)) was reduced (P<.001) versus normal (0.90+/-0.45) and steal (0.92+/-0.60). Nevertheless, in abnormal segments, blood flow increased versus rest (P<.001) with dobutamine (0.83+/-0.43) and adenosine (0.90+/-0.49). In steal segments, myocardial blood flow declined versus baseline (P<.001) with dobutamine (0.68+/-0.46) and adenosine (0.50+/-0.45). In normal segments, myocardial blood flow increased (P<.001) with dobutamine (2.16+/-0.99) and adenosine (3.10+/-0.90). Over the range of flows, the correlation between adenosine and dobutamine was good (r=.78, P<.0001). Although flow with dobutamine in normal segments correlated with rate-pressure product (r=.81, P<.05), the slope of the line was 2.7+/-0.8 (P<.02), and normalized blood flow (3.3+/-2.5 x rest) exceeded normalized rate-pressure product (1.9+/-0.8 x rest; P<.05). CONCLUSIONS: In humans with ischemic heart disease, myocardial blood flow responses to dobutamine and adenosine are linearly correlated over a wide range. The hyperemic response to dobutamine is in excess of that predicted by rate-pressure product and reflects the unmeasured inotropic, oxygen-wasting, and beta2-agonist effects of the drug. Dobutamine induces coronary steal with a frequency approaching that of adenosine.

Adenosine↗
PubMed1997

The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation.

Previous neuroimaging research has contributed insights regarding the neural substrates of specific psychiatric disorders. The purpose of this study was to determine the shared mediating neuroanatomy of anxiety symptoms across three different anxiety disorders. Data were pooled from 23 right-handed adult outpatients meeting criteria for obsessive-compulsive disorder, simple phobia, or posttraumatic stress disorder. Relative regional cerebral blood flow (rCBF) was measured using positron emission tomography in the context of symptom provocation paradigms. Symptom severity was measured via self-reports. The analysis of pooled imaging data indicated activation in right inferior frontal cortex, right posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus control conditions. A positive correlation was found between rCBF at one brain stem locus and subjective anxiety scores (r = .744, p < .001). These findings suggest that elements of the paralimbic belt together with right inferior frontal cortex and subcortical nuclei mediate symptoms across different anxiety disorders. In addition, activation at one brain stem locus appears to be associated with the subjective severity of anxiety. Further studies are warranted to determine whether these same brain systems mediate normal anxiety states as well.

Adult↗
PubMed1997

Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.

BACKGROUND: Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. METHODS: Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. RESULTS: Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. CONCLUSIONS: Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.

Amygdala↗
PubMed1997

Neural systems shared by visual imagery and visual perception: a positron emission tomography study.

Subjects participated in perceptual and imagery tasks while their brains were scanned using positron emission tomography. In the perceptual conditions, subjects judged whether names were appropriate for pictures. In one condition, the objects were pictured from canonical perspectives and could be recognized at first glance; in the other, the objects were pictured from noncanonical perspectives and were not immediately recognizable. In this second condition, we assume that top-down processing is used to evaluate the names. In the imagery conditions, subjects saw a grid with a single X mark; a lowercase letter was presented before the grid. In the baseline condition, they simply responded when they saw the stimulus, whereas in the imagery condition they visualized the corresponding block letter in the grid and decided whether it would have covered the X if it were physically present. Fourteen areas were activated in common by both tasks, only 1 of which may not be involved in visual processing (the precentral gyrus); in addition, 2 were activated in perception but not imagery, and 5 were activated in imagery but not perception. Thus, two-thirds of the activated areas were activated in common.

Adult↗
PubMed1997

Metabolic alterations in muscle of thermally injured rabbits, measured by positron emission tomography.

The hypermetabolic inflammatory state that occurs after major trauma has been extensively studied at the whole body level, however, there is only limited information on metabolic changes in individual tissues. In this study, the effect of thermal injury on metabolic function of uninjured hind limb muscle of rabbits was measured noninvasively by positron emission tomography (PET). Rabbits were subjected to full thickness burn on 25% of their body surface area. Two to three weeks after injury, PET and arterial blood sampling was performed during inhalation of 15O2, C15O2 and 11CO and after injection of 18FDG. The tissue and blood data were analyzed by standard kinetic models for blood flow, oxygen extraction fraction (OEF), oxygen utilization and glucose metabolism. A total of seven injured and five sham animals were studied. Total body oxygen consumption was measured by indirect calorimetry and plasma concentrations of glucose, insulin and IGF-1 were measured with standard assays. Compared to sham rabbits, blood flow to muscle of injured animals was unchanged. However, OEF, oxygen utilization and glucose metabolism were significantly reduced (p<0.01) in uninjured muscle of burned rabbits. These data demonstrate that thermal injury is associated with alterations in muscle metabolism, which are not related to change in blood flow.

Animals↗
PubMed1997

Modeling enrichment kinetics from dynamic 13C-NMR spectra: theoretical analysis and practical considerations.

Measurements of oxidative metabolism in the heart from dynamic 13C nuclear magnetic resonance (NMR) spectroscopy rely on 13C turnover in the NMR-detectable glutamate pool. A kinetic model was developed for the analysis of isotope turnover to determine tricarboxylic acid cycle flux (VTCA) and the interconversion rate between alpha-ketoglutarate and glutamate (F1) by fitting the model to NMR data of glutamate enrichment. The results of data fitting are highly reproducible when the noise level is within 10%, making this model applicable to single or grouped experiments. The values for VTCA and F1 were unchanged whether obtained from least-squares fitting of the model to mean experimental enrichment data with standard deviations in the cost function (VTCA = 10.52 mumol.min-1.g dry wt-1, F1 = 10.67 mumol.min-1.g dry wt-1) or to the individual enrichment values for each heart with the NMR noise level in the cost function (VTCA = 10.67 mumol.min-1.g dry wt-1, F1 = 10.18 mumol.min-1.g dry wt-1). Computer simulation and theoretical analysis indicate that glutamate enrichment kinetics are insensitive to the fractional enrichment of acetyl-CoA and changes in small intermediate pools (< 1 mumol/g dry wt). Therefore, high-resolution NMR analysis of tissue extracts and biochemical assays for intermediates at low concentrations are unnecessary. However, a high correlation between VTCA and F1 exists, as anticipated from competition for alpha-ketoglutarate, which indicates the utility of introducing independent experimental constraints into the data fitting for accurate quantification.

Acetates↗
PubMed1997

Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning.

Positron emission tomography was employed to contrast the brain activation pattern in patients with obsessive-compulsive disorder (OCD) to that of matched control subjects while they performed an implicit learning task. Although patients and control subjects evidenced comparable learning, imaging data from control subjects indicated bilateral inferior striatal activation, whereas OCD patients did not activate right or left inferior striatum and instead showed bilateral medial temporal activation. The findings further implicate corticostriatal dysfunction in obsessive-compulsive disorder. Furthermore, when OCD patients are confronted with stimuli that call for recruitment of corticostriatal systems, they instead appear to access brain regions normally associated with explicit (conscious) information processing.

Adult↗
PubMed1997

The role of positron emission tomography in pharmacokinetic analysis.

The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are likely to be particularly useful: (1) In preclinical studies, a new drug can be precisely compared to standard therapies or a series of analogs can be screened for further development on the basis of performance in appropriate animal models. (2) In phase I-II human studies, classic pharmacokinetic measurements can be coupled with imaging measurements (a) to define optimal dosing schedule; (b) to define the potential utility of interventions in particular clinical situations; and (c) to formulate the design of phase III studies that are crucial for drug licensure. In general, the types of measurements that are possible can be grouped into the following categories: 1. In those situations in which the drug can be radiolabeled, the time course of tissue delivery can be determined noninvasively in vivo in health and disease. Such information should be useful for determining dosing schedules, establishing efficacy, and predicting possible toxicity. 2. Ligand-receptor binding can be assessed in vivo in two ways. The ability of the drug to displace standard radiolabeled ligands from their receptors can be determined; alternatively, labeled drug can be used to more directly assess the distribution and time course of binding. These measurements are particularly useful for studying drugs that are active in the central nervous and cardiovascular systems. 3. Measurements of tissue metabolism will be useful in determining the effects of therapies aimed at particular metabolic abnormalities. In addition, these measurements may be useful in defining viability and function of tissues in such widely disparate clinical situations as cancer chemotherapy and cardiology. For example, effects of CNS or cardiovascular drugs can be monitored by observing 18FDG metabolism in brain and heart. We suggest that the joining of classic clinical pharmacology to exquisite imaging measurements will help form the basis for 21st-century clinical drug development.

Animals↗
PubMed1997

FDG hypermetabolism associated with inflammatory necrotic changes following radiation of meningioma.

PET with 18F-fluoro-2-deoxy-D-glucose (FDG) is currently the noninvasive gold standard for distinguishing brain tumor recurrence from radiation necrosis. We present a case report that appears to contradict this doctrine. The patient had a history of atypical meningioma and was treated with surgical resection and postoperative proton-beam radiation therapy. Approximately 16 mo after completion of therapy, MRI demonstrated two new regions of enhancement, and an FDG-PET study was performed to further characterize these lesions. FDG-PET demonstrated an area of intense hypermetabolism, and wide surgical resection was performed. Histological examination of the surgical specimen revealed reactive changes and areas of necrosis. There was no evidence of either recurrent or radiation-induced tumor.

Aged↗
PubMed1996

Factors influencing regional myocardial contractile response to inotropic stimulation. Analysis in humans with stable ischemic heart disease.

BACKGROUND: We hypothesized that the response of a myocardial segment to maximal dobutamine reflects not only maximal blood flow but also tethering, metabolic, and beta-blocker status. METHODS AND RESULTS: Patients with stable ischemic heart disease (n = 27) had positron emission tomographic measurement of blood flow at rest and with adenosine, and echocardiography at rest and with dobutamine. Positron emission tomographic measurement of [18F]fluorodeoxyglucose myocardial distribution also was made. Adenosine blood flow in segments that contracted normally at peak dobutamine was similar to that of segments that became hypokinetic (1.06 +/- 0.72 versus 1.02 +/- 0.77 mL.g-1.min-1). Segments that became akinetic failed to augment blood flow (0.68 +/- 0.30 mL.g-1.min-1). Fluorodeoxyglucose-blood flow mismatch was more common in segments with abnormal wall motion at peak dobutamine (24 of 59, 41%) versus those that contracted normally (63 of 269, 23%; chi 2, 7.40; P < .01). In patients off beta-blockers, segments that contracted normally at peak dobutamine increased blood flow with adenosine (0.70 +/- 0.31 to 0.86 +/- 0.46 mL.g-1.min-1; P < .05), whereas those that became abnormal did not (0.63 +/- 0.24 to 0.65 +/- 0.19 mL.g-1.min-1; P = NS). Segments of patients on beta-blockers that contracted normally at peak dobutamine increased blood flow with adenosine (0.78 +/- 0.31 to 1.10 +/- 0.70 mL.g-1.min-1; P < .05), as did segments that became abnormal (0.74 +/- 0.34 to 1.06 +/- 0.82 mL.g-1.min-1; P = NS). However, segments adjacent to ones with abnormal wall motion at rest had higher frequency of abnormal response at peak dobutamine in groups on (48% versus 16%; chi 2, 14.1; P < .001) and off (51% versus 21%; chi 2, 10.9; P < .01) beta-blockers. CONCLUSIONS: Augmented contraction at maximal dobutamine depends not only on increased myocardial blood flow but also on tethering, metabolic, and beta-blocker status. Furthermore, impaired flow reserve does not preclude a normal response to maximal dobutamine, since blood flow need not increase greatly to meet demand.

Adenosine↗
PubMed1996

Neural effects of visualizing and perceiving aversive stimuli: a PET investigation.

Cerebral blood flow was recorded (using positron emission tomography) while middle-aged subjects viewed or visualized pictures of neutral or aversive stimuli, and then determined whether auditorily presented statements correctly described the stimuli. Visualizing aversive stimuli enhanced cerebral blood flow, relative to visualizing neutral stimuli, in areas 17 (right) and 18 (bilateral), as well as the anterior insula (bilateral) and middle frontal cortex (left). Areas 17 and 18 have been identified as supporting the representations that underlie the experience of imagery, and the anterior insula is a major cortical recipient of input from the autonomic nervous system. Perceiving aversive stimuli enhanced cerebral blood flow, relative to neutral stimuli, in area 46, the angular gyrus and area 19, area 47, and the middle temporal gyrus (all in the left hemisphere). All of these areas have previously been implicated in visual object identification. It is striking that negative emotion did not modulate activation in any areas in the same way during imagery and perception.

Brain↗
PubMed1996

Subcellular metabolite transport and carbon isotope kinetics in the intramyocardial glutamate pool.

The pathophysiological state of the cell must be translated into the mitochondria to meet the demands for oxidative energy production. Metabolite exchange across the mitochondrial membrane provides this communication and was observed with 13C NMR spectroscopy of hearts oxidizing [2-13C]-butyrate at normal or high cytosolic redox state. Previous NMR observations of 13C turnover within the glutamate pool of intact tissues have indicated its relationship with metabolic flux through the tricarboxylic acid (TCA) cycle, but the direct influence of isotope exchange between the TCA cycle intermediates in the mitochondria and the cytosolic glutamate pool has been much less considered. This current study was designed to determine whether the physical transport of metabolites across the mitochondrial membrane of intact heart tissues could be discerned as a rate determinant for isotope turnover in the NMR-detectable glutamate pool. 13C entry into glutamate provided measures of TCA cycle flux and the interconversion between mitochondrial intermediates and cytosolic glutamate. The influence of the malate-aspartate shuttle activity was examined by comparing two groups of hearts: one group oxidizing 2.5 mM [2-13C]-butyrate (n = 5) and the other oxidizing 2.5 mM [2-13C]butyrate in the presence of a lactate (2.5 mM)-induced elevation in the cytosolic redox to stimulate shuttle activity (n = 5). High redox state did not affect TCA cycle flux but increased the rate of interconversion between alpha-ketoglutarate and glutamate from 3.1 +/- 0.2 mumol min-1 (g dry)-1 to 14.3 +/- 2.0. High resolution 13C NMR spectra of tissue extracts confirmed that the exogenous lactate did not contribute as a carbon source for the formation of either the TCA cycle intermediates or glutamate. In both groups, over 95% of the acetyl-CoA was derived from the short-chain fatty acid butyrate, irrespective of the presence of lactate. Additional hearts perfused with unlabeled butyrate and [3-13C]lactate showed no label entry into glutamate, but rather the formation of [3-13C]alanine, indicating the net reverse flux through lactate dehydrogenase to increase NADH production. Thus, the addition of lactate served only to augment cytosolic redox state to drive the malate-aspartate shuttle. The dynamic-mode acquisition of 13C NMR data from intact hearts, oxidizing [2-13C]-butyrate with or without additional lactate, demonstrated the influence of malate-aspartate shuttle activity on the 13C enrichment rates within glutamate. These data indicate metabolic communication between the mitochondria and cytosol in response to the physiological state of intact tissues.

ATP-Binding Cassette Transporters↗
PubMed1996

The role of hippocampus and frontal cortex in age-related memory changes: a PET study.

The purpose of this study was to examine the neuroanatomical correlates of explicit retrieval of episodic memories in older and young adults. We used an experimental paradigm that allowed us to separate the effort involved in attempting to retrieve a recently studied word from the actual recollection of the item. Both older and younger adults showed hippocampal blood flow increases in association with recollection of a studied word. In contrast, younger but not older adults showed bilateral blood flow increases in anterior prefrontal cortex during retrieval attempts: older adults showed more posterior frontal lobe activations during attempted retrieval. We conclude that the hippocampus activations may reflect a commonality in the way that older and younger adults remember past events, whereas differences in frontal activation may reflect age-related changes in their retrieval strategies.

Adult↗
PubMed1996

Measurement of muscle protein synthesis by positron emission tomography with L-[methyl-11C]methionine.

Positron emission tomography (PET) with L-[methyl-11C]methionine was explored as an in vivo, noninvasive, quantitative method for measuring the protein synthesis rate (PSR) in paraspinal and hind limb muscles of anesthetized dogs. Approximately 25 mCi (1 Ci = 37 GBq) of L-[methyl-11C]methionine was injected intravenously, and serial images and arterial blood samples were acquired over 90 min. Data analysis was performed by fitting tissue- and metabolite-corrected arterial blood time-activity curves to a three-compartment model and assuming insignificant transamination and transmethylation in this tissue. PSR was calculated from fitted parameter values and plasma methionine concentrations. PSRs measured by PET were compared with arterio-venous (A-V) difference measurements across the hind limb during primed constant infusion (5-6 h) of L-[1-13C, methyl-2H3]methionine. Results of PET measurements demonstrated similar PSRs for paraspinal and hind limb muscles: 0.172 +/- 0.062 vs. 0.208 +/- 0.048 nmol-1.min-1.(g of muscle)-1 (P = not significant). PSR determined by the stable isotope technique was 0.27 +/- 0.050 nmol-1.min-1.(g of leg tissue)-1 (P < 0.07 from PET) and indicated that the contribution of transmethylation to total hind limb methionine utilization was approximately 10%. High levels of L-[methyl-11C]methionine utilization by bone marrow were observed. We conclude that muscle PSR can be measured in vivo by PET and that this approach offers promise for application in human metabolic studies.

Animals↗
PubMed1996

Conscious recollection and the human hippocampal formation: evidence from positron emission tomography.

We used positron emission tomography (PET) to examine the role of the hippocampal formation in implicit and explicit memory. Human volunteers studied a list of familiar words, and then they either provided the first word that came to mind in response to three-letter cues (implicit memory) or tried to recall studied words in response to the same cues (explicit memory). There was no evidence of hippocampal activation in association with implicit memory. However, priming effects on the implicit memory test were associated with decreased activity in extrastriate visual cortex. On the explicit memory test, subjects recalled many target words in one condition and recalled few words in a second condition, despite trying to remember them. Comparisons between the two conditions showed that blood-flow increases in the hippocampal formation are specifically associated with the conscious recollection of studied words, whereas blood-flow increases in frontal regions are associated with efforts to retrieve target words. Our results help to clarify some puzzles concerning the role of the hippocampal formation in human memory.

Adult↗