The effect of entacapone on homocysteine levels in Parkinson disease.
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Aged↗
Biomedical subjects
J L Ostrem
Publications and source records attributed to J L Ostrem.
Changing patterns of brain activation during maze learning.
Recent research has found that patterns of brain activation involving the frontal cortex during novel task performance change dramatically following practice and repeat performance. Evidence for differential left vs. right frontal lobe activation, respectively, during episodic memory encoding and retrieval has also been reported. To examine these potentially related issues regional cerebral blood flow (rCBF) was measured in 15 normal volunteers using positron emission tomography (PET) during the naive and practiced performance of a maze task paradigm. SPM analysis indicated a largely right-sided, frontal lobe activation during naive performance. Following training and practice, performance of the same maze task elicited a more posterior pattern of rCBF activation involving posterior cingulate and precuneus. The change in the pattern of rCBF activation between novel and practiced task conditions agrees with results found in previous studies using repeat task methodology, and indicates that the neural circuitry required for encoding novel task information differs from that required when the same task has become familiar and information is being recalled. The right-sided preponderance of activation during naive performance may relate to task novelty and the spatially-based nature of the stimuli, whereas posterior areas activated during repeat performance are those previously found to be associated with visuospatial memory recall. Activation of these areas, however, does not agree with previously reported findings of left-sided activation during verbal episodic memory encoding and right-sided activation during retrieval, suggesting different neural substrates for verbal and visuospatial processing within memory.
Adult↗
Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women.
There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H215O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4-5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.
Adult↗
Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study.
Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks--the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems--and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2 or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task - control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F (1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVA F(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to "focus" neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine.
Adult↗
Cognitive activation during PET: a case study of monozygotic twins discordant for closed head injury.
Using positron emission tomography (PET), we studied physiological changes in a patient with frontal lobe damage resulting from closed head injury by assessing his regional cerebral blood flow (rCBF) pattern relative to that of his uninjured monozygotic (MZ) cotwin and against normal variability between cotwins in 10 comparably-aged, uninjured MZ twin pairs. rCBF was measured during the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Differences between the index twins in rCBF activation (WCST-control) in regions determined on coplanar MRIs were compared to within-pair differences in the control group using the Z-statistic. Activation differences between the index twins extending beyond normal variability were found in two regions-relative to his uninjured cotwin, the injured twin showed less activation in the inferior portion of the left inferior frontal gyrus while showing greater activation in the left hippocampus (P < 0.04). This pattern contrasts with that of normal subjects during WCST performance of augmented rCBF in the prefrontal cortex and not in the hippocampus. These rCBF differences appear to reflect the utilization of different neural systems when performing a frontal-lobe task. The use of the hippocampus by the injured twin might reflect an attempt to compensate for compromised frontal lobe functioning.
Adolescent↗
Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study.
To determine the neural circuitry engaged by performance of the Wisconsin Card Sorting Test (WCST), a neuropsychological test traditionally considered to be sensitive to prefrontal lesions, regional cerebral blood flow was measured with oxygen-15 water and positron emission tomography (PET) while young normal subjects performed the test as well as while they performed a specially designed sensorimotor control task. To consider which of the various cognitive operations and other experiential phenomena involved in the WCST PET scan are critical for the pattern of physiological activation and to focus on the working memory component of the test, repeat WCST scans were also performed on nine of the subjects after instruction on the test and practice to criteria. We confirmed that performance of the WCST engages the frontal cortex and also produces activation of a complex network of regions consistently including the inferior parietal lobule but also involving the visual association and inferior temporal cortices as well as portions of the cerebellum. The WCST activation in the dorsolateral prefrontal cortex (DLPFC) remained significant even after training and practice on the test, suggesting that working memory may be largely responsible for the physiological response in DLPFC during the WCST and, conversely, that the DLPFC plays a major role in modulating working memory.
Adolescent↗
Is there cognitive decline in schizophrenia? A cross-sectional study.
The issue of progressive cognitive decline in patients with schizophrenia has been debated. We performed a cross-sectional study of patients with chronic schizophrenia, aged from 18 to 69 years, in order to address this issue. The patients included in this study passed a rigorous screen for any comorbid condition with an adverse impact on central nervous system function. We assessed intellectual deterioration with a battery of neuropsychological tests known to be sensitive to cognitive impairment in progressive dementia. No evidence of accelerated intellectual decline was found. No significant differences were found between the five age-derived cohorts (18-29, 30-39, 40-49, 50-59, and 60-69 years of age) on the Mini-Mental State Examination, Dementia Rating Scale, or other tests sensitive to dementia. While performance on the Boston Naming Test significantly declined with age, this was mainly due to age rather than duration of illness. However, it is important to note that mean performances on the majority of the tests were abnormal across all cohorts studied. These results suggest that intellectual function does not markedly decline during the adulthood of patients with schizophrenia. The course of schizophrenia is more consistent with a static encephalopathy than a dementing disorder.
Adolescent↗
Effects of eltoprazine hydrochloride on reactivity to conspecific or novel odors and activity.
Treatment with eltoprazine (DU 28853) increased the number of entries by male mice into compartments containing the odors of male and female conspecifics. This effect was most pronounced when odors were provided by previously defeated males. In contrast, the drug had no effect upon responsiveness to the odors of cinnamon and chocolate. The results suggest that eltoprazine may selectively increase reactivity to conspecific odors and that this effect is further enhanced by agonistic experience. Eltoprazine also substantially increased activity levels in all experiments. Since hyperactivity occurred both in the presence and absence of conspecific odors, however, the drug's effects on activity and olfaction seem to be largely independent. The results suggest that the aggression-modulating effects of eltoprazine, as well as other drugs, may be mediated in part by their effects on normal olfactory function.
Aggression↗