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Biomedical subjects

Sarah M Brown

Publications and source records attributed to Sarah M Brown.

8 recordsLinked to original sources

Preference for immediate over delayed rewards is associated with magnitude of ventral striatal activity.

Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation level-dependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.

Adult↗

Human choline transporter gene variation is associated with corticolimbic reactivity and autonomic-cholinergic function.

BACKGROUND: Our previous work has shown genetic variation in the human choline transporter gene (CHT1) to be associated with depressive symptoms and autonomic cardiac (cholinergic) dysregulation. Here, functional magnetic resonance imaging (fMRI) was used to examine the relation between a single nucleotide polymorphism (SNP) in CHT1 on regional brain reactivity relevant to autonomic (cholinergic) function. METHODS: Thirty-two participants of European ancestry (18 men, 14 women; age: 33-54 years) completed an fMRI protocol using corticolimbic reactivity and prefrontal inhibitory control paradigms. Resting cholinergic function, as measured by heart rate variability (HRV), was quantified from electrocardiogram. Subjects were genotyped for a CHT1 G/T SNP. RESULTS: GG homozygotes had greater right (R) dorsal amygdala (p < .008), bilateral anterior cingulate (p < .009), and R caudate reactivity (p < .015) than T-allele carriers. Heart rate variability was related to R frontal cortex (Brodmann Areas 6, 9, and 46), R hippocampal formation, bilateral caudate, and bilateral anterior cingulate reactivity (p's < .007). CONCLUSIONS: CHT1 variation is related to differences in a distributed corticolimbic circuitry mediating behavioral and physiologic arousal. These relations may contribute to a biological mechanism by which genetic variation in cholinergic neurotransmission affects cognition, mood, and autonomic cardiac function.

Adult↗

Neural basis of individual differences in impulsivity: contributions of corticolimbic circuits for behavioral arousal and control.

The objective of the current study was to analyze the neural correlates of behavioral arousal and inhibitory control as they relate to individual differences in impulsivity via well-established functional MRI amygdala reactivity and prefrontal inhibitory control paradigms in healthy adult subjects. Impulsivity correlated positively with activity of the bilateral ventral amygdala, parahippocampal gyrus, dorsal anterior cingulate gyrus (BA 32), and bilateral caudate. Conversely, impulsivity correlated negatively with activity of the dorsal amygdala and ventral prefrontal cortex (BA 47). Together, these findings suggest that dispositional impulsivity is influenced by the functional interplay of corticolimbic behavioral arousal and control circuits.

Adult↗

Serotonin.

Explore the source record for details and available documents.

Amygdala↗

Neuroimaging studies of serotonin gene polymorphisms: exploring the interplay of genes, brain, and behavior.

Because of the unique ability it provides to investigate information processing at the level of neural systems, functional neuroimaging is a powerful tool to explore the relationship between genes, brain, and behavior. Recently, functional neuroimaging has provided dramatic illustrations of how a promoter polymorphism in the human serotonin transporter gene, which has been weakly related to several dimensions of emotional behaviors (such as neuroticism and anxiety traits), is strongly related to the engagement of neural systems--namely, the amygdala and subgenual prefrontal cortex, subserving emotional information processing. This review will outline the experimental strategy by which these genetic effects on brain function have been explored and highlight the effectiveness of this strategy to delineate biological pathways and mechanisms contributing to the emergence of individual differences in brain function that potentially bias behavior and risk for psychiatric illness.

Animals↗

Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex.

Prefrontal cortex is a target for glucocorticoids, shows neurochemical changes in response to stress and mediates many of the behaviors that are altered by chronic corticosterone administration. Three weeks of either daily corticosterone injections or 3 h daily restraint stress result in dendritic changes in pyramidal neurons in medial prefrontal cortex. Interestingly, vehicle injection results in similar but less pronounced changes. Thus, the mild stress of daily injections alone may alter morphology of medial prefrontal cortex, suggesting an exquisite sensitivity to chronic stress. To further examine this morphological sensitivity, we assessed the effect of 1 week of daily brief restraint stress on dendritic morphology in medial prefrontal cortex. Male rats were restrained 10 min per day for one week, handled daily or left unhandled. Rats were then overdosed and brains were stained using a Golgi-Cox procedure. Layer II-III pyramidal neurons in medial prefrontal cortex were drawn and dendritic morphology was quantified. One week of daily brief restraint resulted in selective remodeling of apical dendrites, with atrophy of up to 22-35% in distal branches and sparing of proximal branches. This pattern of reorganization is similar to that seen after either corticosterone injections or 3 weeks of daily 3 h restraint stress. Thus, the stress-induced dendritic changes in medial prefrontal cortex occur rapidly, and in response to a mild stressor.

Adaptation, Physiological↗

Tissue-specific variation in glycation of proteins in diabetes: evidence for a functional role of amadoriase enzymes.

The Amadori product fructoselysine (FL), an intermediate in the formation of many advanced glycation end products, may be deglycated by various pathways. These include spontaneous chemical degradation or enzymatic deglycation by amadoriases. This study was designed to compare changes in FL in various tissues in response to changes in glycemia, thereby testing tissue-specific deglycation. FL content in skin collagen, red cell hemoglobin, and total muscle, liver, and brain protein was analyzed by isotope dilution gas chromatography-mass spectrometry. Mean blood glucose increased over fourfold in diabetic versus control rats, whereas changes in glycation of proteins varied from fivefold in collagen to no change in the liver and brain. These results suggest significant differences among tissues in the activity of deglycating enzymes and/or protein turnover.

Amino Acid Oxidoreductases↗

Evidenced-based factors in readmission of patients with heart failure.

The purpose of this project was to organize the variables associated with the hospital readmission of patients with heart failure (HF) into a usable framework to inform clinical practice and facilitate administrative decision making. An integrated, systematic review of the literature was used as the research approach. A content analysis of the sample (31 research reports from the years 1986-2004) yielded multiple factors associated with the hospital readmission of HF patients. Factors and their definitions were extracted, grouped into like categories, and eventually classified into 5 domains-demographic, physiologic, psychosocial, patient functioning, and resource utilization. The resulting framework has clinical, research, and administrative implications in the delivery of care to HF patients.

Activities of Daily Living↗