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N M Alpert

Publications and source records attributed to N M Alpert.

At least 19 recordsLinked to original sources
PubMed2001

[(11)C, (127)I] Altropane: a highly selective ligand for PET imaging of dopamine transporter sites.

The E isomer of (123)I-2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl)nortropane (Altropane(R)) shows high affinity (IC(50) = 6.62 +/- 0.78 nmol) and selectivity (DA/5-HT = 25) for DAT sites in the striatum. Recently, dynamic SPECT studies in healthy volunteers and patients with Parkinson disease demonstrated that the kinetics of striatal accumulation followed a pattern that is characteristic of a reversible tracer with maximal accumulation within 30 min after injection. These findings suggested that radiolabeling Altropane with [(11)C] might provide an equivalent and complementary tracer for PET studies. [(127)I] Altropane was treated with HCl to hydrolyze the methyl ester bond and yield a precursor for [(11)C] labeling. Introduction of an [(11)C] methyl ester group was achieved by treatment with [(11)C] CH(3)I followed by HPLC purification. Five healthy rhesus monkeys were injected with approximately 10 mCi of [(127)I,(11)C] Altropane and dynamic PET images were acquired over 90 min. Arterial blood samples were collected in parallel with imaging and metabolite analysis was performed by HPLC. The PET and metabolite corrected arterial blood data were to calculate k(3)/k(4) by two methods: 1) nonlinear least-squares fitting, and 2) a linear graphical method for reversible ligands. The synthetic procedure yielded high specific activity tracer, >1,000 mCi/micro mole, with radiochemical purity >95%. Synthesis time was approximately 30 min. The PET images revealed excellent striatal definition, with clear separation of caudate nucleus and putamen and minimal accumulation in brain regions with high 5HT transporter density. Metabolite analysis demonstrated that at 60 min after injection, approximately 80% of circulating tracer was intact [(127)I,(11)C] Altropane and the remainder was converted to polar metabolites. Values for k(3)/k(4) calculated by two analysis methods were remarkably similar: Method 1, 3.48 +/- 0.41; Method 2, 3.77 +/- 0.45 (mean +/- SEM, t = 2.31, df = 8, P = 0.64). These results establish that Altropane has the important characteristics of: 1) rapid and specific striatal binding; 2) high selectivity for DA vs. 5-HT transporter sites; 3) reversible binding kinetics; 4) potential for multiple injection studies; 5) high efficiency labeling with either [(11)C] or [(123)I]; 6) applicability for both PET and SPECT. These properties make Altropane an important DAT ligand for both research and clinical applications.

Animals↗
PubMed2001

Priming within and across modalities: exploring the nature of rCBF increases and decreases.

Neuroimaging studies suggest that within-modality priming is associated with reduced regional cerebral blood flow (rCBF) in the extrastriate area, whereas cross-modality priming is associated with increased rCBF in prefrontal cortex. To characterize the nature of rCBF changes in within- and cross-modality priming, we conducted two neuroimaging experiments using positron emission tomography (PET). In experiment 1, rCBF changes in within-modality auditory priming on a word stem completion task were observed under same- and different-voice conditions. Both conditions were associated with decreased rCBF in extrastriate cortex. In the different-voice condition there were additional rCBF changes in the middle temporal gyrus and prefrontal cortex. Results suggest that the extrastriate involvement in within-modality priming is sensitive to a change in sensory modality of target stimuli between study and test, but not to a change in the feature of a stimulus within the same modality. In experiment 2, we studied cross-modality priming on a visual stem completion test after encoding under full- and divided-attention conditions. Increased rCBF in the anterior prefrontal cortex was observed in the full- but not in the divided-attention condition. Because explicit retrieval is compromised after encoding under the divided-attention condition, prefrontal involvement in cross-modality priming indicates recruitment of an aspect of explicit retrieval mechanism. The aspect of explicit retrieval that is most likely to be involved in cross-modality priming is the familiarity effect.

Adult↗
PubMed2001

Neural substrates of anorexia nervosa: a behavioral challenge study with positron emission tomography.

OBJECTIVE: To delineate functional brain abnormalities associated with anorexia nervosa (AN). STUDY DESIGN: Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were performed on 8 female patients with AN and 8 healthy female control subjects during exposure to 3 types of stimuli: high-calorie foods, low-calorie foods, and non-food items. Heart rate and internal state analog scale scores were also obtained. Stereotactic transformation and statistical parametric mapping techniques were used to analyze imaging data. RESULTS: During the high-calorie condition, control subjects reported a significant desire to eat, whereas subjects with AN reported elevated anxiety and exhibited increases in heart rate. Patients with AN had elevated bilateral medial temporal lobe rCBF compared with control subjects. Planned comparisons for group-by-condition interactions demonstrated greater activation within left occipital cortex and right temporo-occipital cortex for the high-calorie versus low-calorie contrast in patients with AN compared with control subjects. CONCLUSIONS: Our finding of elevated rCBF within bilateral medial temporal lobes is similar to published results in patients with psychotic disorders and may be related to the body image distortion common to AN. The high-calorie food phobia exhibited by patients with AN appears to be associated with exaggerated responses in visual association cortex, as has been previously observed in studies of specific phobias.

Adult↗
PubMed2001

Prefrontal regions supporting spontaneous and directed application of verbal learning strategies: evidence from PET.

The prefrontal cortex has been implicated in strategic memory processes, including the ability to use semantic organizational strategies to facilitate episodic learning. An important feature of these strategies is the way they are applied in novel or ambiguous situations-failure to initiate effective strategies spontaneously in unstructured settings is a central cognitive deficit in patients with frontal lobe disorders. The current study examined strategic memory with PET and a verbal encoding paradigm that manipulated semantic organization in three encoding conditions: spontaneous, directed and unrelated. During the spontaneous condition, subjects heard 24 words that were related in four categories but presented in mixed order, and they were not informed of this structure beforehand. Any semantic reorganization was, therefore, initiated spontaneously by the subject. In the directed condition, subjects were given a different list of 24 related words and explicitly instructed to notice relationships and mentally group related words together to improve memory. The unrelated list consisted of 24 unrelated words. Behavioural measures included semantic clustering, which assessed active regrouping of words into semantic categories during free recall. In graded PET contrasts (directed > spontaneous > unrelated), two distinct activations were found in left inferior prefrontal cortex (inferior frontal gyrus) and left dorsolateral prefrontal cortex (middle frontal gyrus), corresponding to levels of semantic clustering observed in the behavioural data. Additional covariate analyses in the first spontaneous condition indicated that blood flow in orbitofrontal cortex (OFC) was strongly correlated with semantic clustering scores during immediate free recall. Thus, blood flow in OFC during encoding predicted which subjects would spontaneously initiate effective strategies during free recall. Our findings indicate that OFC performs an important, and previously unappreciated, role in strategic memory by supporting the early mobilization of effective behavioural strategies in novel or ambiguous situations. Once initiated, lateral regions of left prefrontal cortex control verbal semantic organization.

Acoustic Stimulation↗
PubMed2000

Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia.

BACKGROUND: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. METHODS: We used (15)O positron emission tomography to study regional cerebral blood flow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task. RESULTS: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. CONCLUSIONS: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia.

Adult↗
PubMed2000

Activation of anterior paralimbic structures during guilt-related script-driven imagery.

BACKGROUND: Several recent neuroimaging studies have examined the neuroanatomical correlates of normal emotional states, such as happiness, sadness, fear, anger, anxiety, and disgust; however, no previous study has examined the emotional state of guilt. METHODS: In the current study, we used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the transient emotional experience of guilt in eight healthy male participants. In the Guilt condition, participants recalled and imagined participating in a personal event involving the most guilt they had ever experienced. In the Neutral condition, participants recalled and imagined participating in an emotionally neutral personal event. RESULTS: In the Guilt versus Neutral comparison, rCBF increases occurred in anterior paralimbic regions of the brain: bilateral anterior temporal poles, anterior cingulate gyrus, and left anterior insular cortex/inferior frontal gyrus. CONCLUSIONS: These results, along with those of previous studies, are consistent with the notion that anterior paralimbic regions of the brain mediate negative emotional states in healthy individuals.

Adult↗
PubMed2000

Neuroanatomy of human appetitive function: A positron emission tomography investigation.

OBJECTIVE: The mediating neuroanatomy of human appetitive function is poorly understood. A state induction paradigm was employed, in conjunction with positron emission tomography, to test the hypothesis that limbic/paralimbic regions respond to the desirability of food stimuli. METHODS: Eight normal subjects were studied during each of three conditions, involving visual exposure to high-caloric food, low-caloric food, and nonfood stimuli. Subjective indices of hunger were measured via analog scales. RESULTS: Planned contrasts demonstrated significant increases in desire to eat and decreases in left temporoinsular cortical blood flow during the high-caloric versus control conditions. DISCUSSION: Results implicate the temporo-insular cortex in normal appetitive function, suggesting that activity within this region is associated with the desirability or valence of food stimuli, prior to ingestion. These data will provide a broad foundation for future studies of patients with eating disorders.

Adult↗
PubMed2000

Evidence of reduced resting blood flow in viable myocardial regions with chronic asynergy.

OBJECTIVES: We tested the hypothesis in patients (n = 24) with ischemic heart disease that chronic contractile dysfunction occurs in myocardial regions with true reduction in rest blood flow. BACKGROUND: Whether viable myocardial regions with chronic contractile dysfunction have true reduction in rest myocardial blood flow is controversial. METHODS: Positron emission tomography (PET) 13N-ammonia was used to measure myocardial blood flow in combination with 18F-fluorodeoxyglucose (18FDG) to assess myocardial viability. Viability also was assessed by dobutamine echo and recovery of function after coronary artery bypass grafting (CABG). Segments (n = 252) were selected based on PET measured reduced resting blood flow and rest asynergy on echo. RESULTS: Regional myocardial viability was present in 20 of 23 patients by PET, 13 of 23 by dobutamine echo and 10 of 11 by postrevascularization criteria. Rest blood flow in normal regions was 1.14+/-0.52 ml/min/g and by definition exceeded (p < 0.005) that in both viable (0.48+/-0.15; n = 8 patients) and nonviable (0.45+/-0.14; n = 8 patients) regions (post-CABG criteria), which did not differ. Correction of rest myocardial blood flow in viable asynergic segments, only, for fibrosis and incomplete tracer recovery raised the level to 0.67+/-0.21 (p < 0.005 vs. normal). Finally, evidence of both stunning (rest asynergy with normal flow) and hibernation was present in 15 of 23 (65%) patients. CONCLUSIONS: Reduced rest blood flow in viable myocardial regions with chronic asynergy is common and cannot be accounted for by partial volume effect. Thus, hypotheses concerning physiologic mechanisms underlying chronic contractile dysfunction should consider the role played by chronic reduction of basal myocardial blood flow.

Adult↗
PubMed2000

Hypnotic visual illusion alters color processing in the brain.

OBJECTIVE: This study was designed to determine whether hypnosis can modulate color perception. Such evidence would provide insight into the nature of hypnosis and its underlying mechanisms. METHOD: Eight highly hypnotizable subjects were asked to see a color pattern in color, a similar gray-scale pattern in color, the color pattern as gray scale, and the gray-scale pattern as gray scale during positron emission tomography scanning by means of [(15)O]CO(2). The classic color area in the fusiform or lingual region of the brain was first identified by analyzing the results when subjects were asked to perceive color as color versus when they were asked to perceive gray scale as gray scale. RESULTS: When subjects were hypnotized, color areas of the left and right hemispheres were activated when they were asked to perceive color, whether they were actually shown the color or the gray-scale stimulus. These brain regions had decreased activation when subjects were told to see gray scale, whether they were actually shown the color or gray-scale stimuli. These results were obtained only during hypnosis in the left hemisphere, whereas blood flow changes reflected instructions to perceive color versus gray scale in the right hemisphere, whether or not subjects had been hypnotized. CONCLUSIONS: Among highly hypnotizable subjects, observed changes in subjective experience achieved during hypnosis were reflected by changes in brain function similar to those that occur in perception. These findings support the claim that hypnosis is a psychological state with distinct neural correlates and is not just the result of adopting a role.

Adult↗
PubMed2000

Comparison of 4 methods for quantification of dopamine transporters by SPECT with [123I]IACFT.

UNLABELLED: 2Beta-carbomethoxy-3beta-(4-fluorophenyl)-n-(1-iodoprop-1-en -3-yl) nortropane (IACFT) is a highly selective ligand for dopamine transporter (DAT) sites in the striatum. Recent reports have described the basic kinetics, neurobiology, and imaging properties of [123I]IACFT. This report focuses on the structural (i.e., the ability to produce consistent binding estimates) validity of 4 methods to quantify striatal binding potential (BP) for IACFT. METHODS: Seven healthy volunteers and 8 patients with Parkinson's disease were subjects for this study. Dynamic SPECT images and arterial blood samples were acquired during the 1.5-2 h after injection of 185-370 MBq [123I]IACFT. Plasma radioactivity was analyzed chromatographically to obtain metabolite-corrected arterial input functions. The k3/k4 ratio (BP) for striatal DAT sites was calculated by 4 methods. In the first method, tissue time-activity curves and metabolite-corrected arterial input functions were analyzed by a linear graphic method developed for reversible receptor ligands. The second method was also graphic; however, the occipital cortex time-activity curve was used as the input function. In the third method, the difference between the striatal and occipital cortex time-activity curves at secular equilibrium was taken to represent bound tracer, the occipital cortex time-activity curve was used to represent tracer in the free and nonspecifically bound state, and equilibrium receptor equations were used to determine BP. The fourth method used the occipital cortex time-activity curve to mathematically derive an input function for fitting the striatal time-activity curve and to determine BP. RESULTS: Analysis of the dynamic SPECT data by methods 1 and 2 resulted in highly linear plots (after approximately 15 min), supporting the reversibility of the tracer. A high linear correlation was found for BP determined by all 4 methods. ANOVA showed that methods 1-3 were indistinguishable; method 4 yielded lower BPs than did methods 1-3. CONCLUSION: These results show that BP can be estimated consistently using 4 different methods. This finding lends support to the modeling assumptions and provides methods suitable for clinical investigation.

Adult↗
PubMed1999

Anger in healthy men: a PET study using script-driven imagery.

BACKGROUND: An understanding of the neurobiological basis of normal emotional processing is useful in formulating hypotheses regarding the pathophysiology of psychiatric illnesses. METHODS: This study examined the mediating functional neuroanatomy of anger in eight healthy men. Narrative scripts were developed from autobiographical information to induce anger and neutral states. The subjects imagined the content of the narrative scripts to induce anger during positron emission tomography to measure normalized regional cerebral blood flow (rCBF). Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Statistical parametric maps were constructed to reflect the Anger versus Neutral state contrast. RESULTS: Anger was associated with activation of the left orbitofrontal cortex, right anterior cingulate cortex affective division, and bilateral anterior temporal poles. CONCLUSIONS: These results suggest that the subjective experience of anger is associated with rCBF increases in anterior paralimbic regions of the brain.

Adult↗
PubMed1999

Neural activation during sexual and competitive arousal in healthy men.

To investigate the mediating neuroanatomy of positively valenced arousal, we used script-driven imagery in conjunction with positron emission tomography to measure relative regional cerebral blood flow (rCBF) during sexual and competitive arousal, as well as neutral comparison states. Subjects were eight healthy right-handed men. Psychophysiologic responses and subjective ratings confirmed that the desired state manipulations were achieved. Statistical parametric mapping revealed similar patterns of rCBF changes for both positively valenced arousal conditions: increases were found within anterior cingulate and anterior temporal cortex as well as the ventral globus pallidus; decreases were found within widespread heteromodal association areas. These results complement findings from studies of other normal and pathological emotional states, and provide new insights regarding the neural substrates of pleasurable arousal in healthy men.

Adult↗
PubMed1999

Visual word stem completion priming within and across modalities: a PET study.

Using positron emission tomography, we studied changes in the regional cerebral blood flow (rCBF) associated with cross modality (auditory to visual) and within modality visual priming in a word stem completion task. Compared to baseline completion performance and to within modality visual priming, cross modality priming was associated with increased rCBF in prefrontal cortex and decreased rCBF in the left angular gyrus. The results confirm and complement trends observed in a previous study concerning visual to auditory cross modality priming, and suggest that distinct cortical mechanisms may mediate within- and cross modality priming on the stem completion task. The findings are consistent with the neuropsychological data concerning auditory to visual cross modality priming, and indicate involvement of aspects of explicit retrieval and lexical processes in cross modality priming.

Acoustic Stimulation↗
PubMed1999

Relation between coronary "steal" and contractile function at rest in collateral-dependent myocardium of humans with ischemic heart disease.

BACKGROUND: We tested the hypothesis that rest asynergy in collateral-dependent myocardium correlates with coronary steal. METHODS AND RESULTS: PET with [13N]ammonia measured myocardial blood flow and flow reserve in 15 patients with symptomatic chronic ischemic heart disease. Coronary angiography assessed stenosis severity and collateral blood supply. Echocardiography or contrast ventriculography evaluated regional wall motion. Collateral-dependent segments with normal flow at rest and supplied by coronary vessels having </=50% diameter stenosis were studied. Steal was defined as a decline in myocardial blood flow with adenosine >/=0.15 mL. min-1. g-1 versus rest. Blood flow at rest in asynergic, collateral-dependent segments with steal (1.15+/-0.35 mL. min-1. g-1) exceeded (P<0.0001) that of asynergic segments without steal (0.81+/-0.24) and those with normal contraction (0.77+/-0.18). Although the flow reserve ratio of segments with normal contraction (1.8+/-0.8) exceeded that of asynergic ones with (0.6+/-0.1) or without (1.3+/-0.4) steal, overlap was great. Correlation between basal contraction and flow reserve ratio in collateral-dependent myocardium was significant but weak (r=0.45, P<0.001). However, segments demonstrating "steal" with adenosine manifested asynergy in 22 of 23 collateral-dependent segments versus 24 of 39 nonsteal segments (chi2=7.10, P<0.01). CONCLUSIONS: Although myocardial flow reserve in collateral-dependent segments with normal contraction exceeded that of asynergic segments, overlap was great. However, in patients with angina or congestive heart failure, left ventricular segments demonstrating steal with adenosine almost always exhibit asynergy at rest. Thus, coronary steal may play an important role in the pathogenesis of chronic contractile impairment at rest, whereas simple reduction of flow reserve may be less important in selected patients.

Aged↗
PubMed1999

The role of area 17 in visual imagery: convergent evidence from PET and rTMS.

Visual imagery is used in a wide range of mental activities, ranging from memory to reasoning, and also plays a role in perception proper. The contribution of early visual cortex, specifically Area 17, to visual mental imagery was examined by the use of two convergent techniques. In one, subjects closed their eyes during positron emission tomography (PET) while they visualized and compared properties (for example, relative length) of sets of stripes. The results showed that when people perform this task, Area 17 is activated. In the other, repetitive transcranial magnetic stimulation (rTMS) was applied to medial occipital cortex before presentation of the same task. Performance was impaired after rTMS compared with a sham control condition; similar results were obtained when the subjects performed the task by actually looking at the stimuli. In sum, the PET results showed that when patterns of stripes are visualized, Area 17 is activated, and the rTMS results showed that such activation underlies information processing.

Adult↗
PubMed1999

Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia.

BACKGROUND: Neuroimaging studies have provided evidence of abnormal frontal and temporal lobe function in schizophrenia. Frontal cortex abnormalities have been associated with negative symptoms and temporal lobe abnormalities with positive symptoms. The deficit and nondeficit forms of schizophrenia were predicted to differ in prefrontal cortical activity, but not in medial temporal lobe activity. METHODS: Regional cerebral blood flow was studied using oxygen 15 positron emission tomography during 3 different memory retrieval conditions in 8 control subjects, 8 patients with the deficit syndrome, and 8 patients without the deficit syndrome. Behavioral and positron emission tomography data were analyzed using a mixed-effects model to test for population differences. RESULTS: In all memory conditions, frontal cortex activity was higher in patients without the deficit syndrome than in patients with the deficit syndrome. During the attempt to retrieve poorly encoded words, patients without the deficit syndrome recruited the left frontal cortex to a significantly greater degree than did patients with the deficit syndrome. The 2 schizophrenia subtypes did not differ in the activity or recruitment of the hippocampus during memory retrieval. CONCLUSION: Frontal cortex function during memory retrieval is differentially impaired in deficit and nondeficit schizophrenia, whereas hippocampal recruitment deficits are not significantly different between the 2 schizophrenia groups.

Adult↗