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Biomedical subjects

C L Larson

Publications and source records attributed to C L Larson.

At least 19 recordsLinked to original sources
PubMed2004

Functional but not structural subgenual prefrontal cortex abnormalities in melancholia.

Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia--a subtype of depression characterized by anhedonia--but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5-6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.

Adult↗
PubMed2001

Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis.

OBJECTIVE: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG. METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. RESULTS: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. CONCLUSIONS: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.

Adult↗
PubMed2000

Dysfunction in the neural circuitry of emotion regulation--a possible prelude to violence.

Emotion is normally regulated in the human brain by a complex circuit consisting of the orbital frontal cortex, amygdala, anterior cingulate cortex, and several other interconnected regions. There are both genetic and environmental contributions to the structure and function of this circuitry. We posit that impulsive aggression and violence arise as a consequence of faulty emotion regulation. Indeed, the prefrontal cortex receives a major serotonergic projection, which is dysfunctional in individuals who show impulsive violence. Individuals vulnerable to faulty regulation of negative emotion are at risk for violence and aggression. Research on the neural circuitry of emotion regulation suggests new avenues of intervention for such at-risk populations.

Affect↗
PubMed2000

Six-month test-retest reliability of MRI-defined PET measures of regional cerebral glucose metabolic rate in selected subcortical structures.

Test-retest reliability of resting regional cerebral metabolic rate of glucose (rCMR) was examined in selected subcortical structures: the amygdala, hippocampus, thalamus, and anterior caudate nucleus. Findings from previous studies examining reliability of rCMR suggest that rCMR in small subcortical structures may be more variable than in larger cortical regions. We chose to study these subcortical regions because of their particular interest to our laboratory in its investigations of the neurocircuitry of emotion and depression. Twelve normal subjects (seven female, mean age = 32.42 years, range 21-48 years) underwent two FDG-PET scans separated by approximately 6 months (mean = 25 weeks, range 17-35 weeks). A region-of-interest approach with PET-MRI coregistration was used for analysis of rCMR reliability. Good test-retest reliability was found in the left amygdala, right and left hippocampus, right and left thalamus, and right and left anterior caudate nucleus. However, rCMR in the right amygdala did not show good test-retest reliability. The implications of these data and their import for studies that include a repeat-test design are considered.

Adult↗
PubMed2000

Dietary composition and physiologic adaptations to energy restriction.

BACKGROUND: The concept of a body weight set point, determined predominantly by genetic mechanisms, has been proposed to explain the poor long-term results of conventional energy-restricted diets in the treatment of obesity. OBJECTIVE: The objective of this study was to examine whether dietary composition affects hormonal and metabolic adaptations to energy restriction. DESIGN: A randomized, crossover design was used to compare the effects of a high-glycemic-index (high-GI) and a low-glycemic-index (low-GI) energy-restricted diet. The macronutrient composition of the high-GI diet was (as percent of energy) 67% carbohydrate, 15% protein, and 18% fat and that of the low-GI diet was 43% carbohydrate, 27% protein, and 30% fat; the diets had similar total energy, energy density, and fiber contents. The subjects, 10 moderately overweight young men, were studied for 9 d on 2 separate occasions. On days -1 to 0, they consumed self-selected foods ad libitum. On days 1-6, they received an energy-restricted high- or low-GI diet. On days 7-8, the high- or low-GI diets were consumed ad libitum. RESULTS: Serum leptin decreased to a lesser extent from day 0 to day 6 with the high-GI diet than with the low-GI diet. Resting energy expenditure declined by 10.5% during the high-GI diet but by only 4.6% during the low-GI diet (7.38 +/- 0.39 and 7.78 +/- 0.36 MJ/d, respectively, on days 5-6; P = 0.04). Nitrogen balance tended to be more negative, and energy intake from snacks on days 7-8 was greater, with the high-GI than the low-GI diet. CONCLUSION: Diets with identical energy contents can have different effects on leptin concentrations, energy expenditure, voluntary food intake, and nitrogen balance, suggesting that the physiologic adaptations to energy restriction can be modified by dietary composition.

Adaptation, Physiological↗
PubMed2000

Temporal stability of the emotion-modulated startle response.

In the present study, we examined the stability of one measure of emotion, the emotion-modulated acoustic startle response, in an undergraduate sample. Using the acoustic startle paradigm on two different occasions, we measured stability of affective modulation of the startle response during and following the presentation of pictures selected to be of positive, negative, or neutral emotional valence. The two assessments were separated by 4 weeks. Two groups of subjects were compared: one group that viewed the same pictures at each assessment and a second group that viewed different pictures at the second assessment. We found that viewing different pictures at two assessments separated by 4 weeks yielded moderate stability of the emotion modulation of startle magnitude, whereas subjects who viewed the same pictures at both assessments showed poor stability. Furthermore, this difference was due to the stability of responses to high versus low arousal pictures, not to differences in valence.

Adolescent↗
PubMed2000

Suppression and enhancement of emotional responses to unpleasant pictures.

Despite the prominence of emotional dysfunction in psychopathology, relatively few experiments have explicitly studied emotion regulation in adults. The present study examined one type of emotion regulation: voluntary regulation of short-term emotional responses to unpleasant visual stimuli. In a sample of 48 college students, both eyeblink startle magnitude and corrugator activity were sensitive to experimental manipulation. Instructions to suppress negative emotion led to both smaller startle eyeblinks and decreased corrugator activity. Instructions to enhance negative emotion led to larger startle eyeblinks and increased corrugator activity. Several advantages of this experimental manipulation are discussed, including the use of both a suppress and an enhance emotion condition, independent measurement of initial emotion elicitation and subsequent regulation of that emotion, the use of a completely within-subjects design, and the use of naturalistic emotion regulation strategies.

Adult↗
PubMed1999

Thalamic metabolic rate predicts EEG alpha power in healthy control subjects but not in depressed patients.

BACKGROUND: EEG alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The hypothesis that the thalamus serves as a neuronal oscillator of alpha rhythms has been supported by studies in animals, but only minimally by studies in humans. METHODS: In the current study, PET-derived measures of regional glucose metabolism, EEG, and structural MRI were obtained from each participant to assess the relation between thalamic metabolic activity and alpha power in depressed patients and healthy controls. The thalamus was identified and drawn on each subject's MRI. The MRI was then co-registered to the corresponding PET scan and metabolic activity from the thalamus extracted. Thalamic activity was then correlated with a 30-min aggregated average of alpha EEG power. RESULTS: Robust inverse correlations were observed in the control data, indicating that greater thalamic metabolism is correlated with decreased alpha power. No relation was found in the depressed patient data. CONCLUSIONS: The results are discussed in the context of a possible abnormality in thalamocortical circuitry associated with depression.

Adult↗
PubMed1999

EEG alpha power and alpha power asymmetry in sleep and wakefulness.

Asymmetry of waking electroencephalography (EEG) alpha power in frontal regions has been correlated with waking emotional reactivity and the emotional content of dream reports. Little is known regarding alpha asymmetry during sleep. The present study was performed to compare alpha power and alpha power asymmetry in various brain regions across states of sleep and wakefulness. Waking and sleep EEG were recorded in a group of patients undergoing polysomnographic evaluation for possible sleep disorders. Alpha EEG asymmetry in frontal and temporal regions was significantly correlated in waking versus sleep, particularly during rapid eye movement (REM) sleep. These results suggest that patterns of frontal alpha asymmetry are stable across sleep and waking and may be related to emotional reactivity during dreaming. During sleep, alpha power was highest during slow-wave sleep and lowest during REM sleep. Implications of these data for understanding the functional significance of alpha power during waking and sleeping are considered.

Adult↗
PubMed1998

Metabolic rate in the right amygdala predicts negative affect in depressed patients.

The role of the amygdala in major depression was investigated. Resting regional cerebral metabolic rate (rCMRglu) was measured with [18F]fluorodeoxyglucose positron emission tomography (PET) in two samples of subjects using two different PET cameras. The samples consisted of 10 and 17 medication-free depressives and 11 and 13 controls, respectively. Using coregistration of PET and magnetic resonance images, regions were individually delineated for the amygdala and thalamus, the latter of which was used as a control region. Within the depressed groups, right amygdalar rCMRglu was positively correlated with negative affect. Thalamic rCMRglu was not related to negative affect, and amygdalar rCMRglu accounted for a significant portion of variance in depressives' negative affect scores over and above the contribution of thalamic rCMRglu.

Amygdala↗
PubMed1998

Relations between PET-derived measures of thalamic glucose metabolism and EEG alpha power.

Electroencephalogram (EEG) alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have suggested that cortical alpha rhythms are correlated with alpha rhythms in the thalamus. However, little empirical evidence exists for this relation in humans. In the current study, resting EEG and a fluorodeoxyglucose positron emission tomography scan were measured during the same experimental session. Over a 30-min period, average EEG alpha power across 28 electrodes from 27 participants was robustly inversely correlated with glucose metabolic activity in the thalamus. These data provide the first evidence for a relation between alpha EEG power and thalamic activity in humans.

Adult↗
PubMed1997

Telemedicine's role in UI statewide service.

Rapid innovation in telecommunications technology means big changes for many professions, medicine included. Telemedicine--defined as the electronic transmission of medical information and services from one place to another--is widely heralded, but questions of how and when it should be used remain.

Humans↗
PubMed1979

Effect of visceral leishmaniasis on congenitally athymic mice.

Congenitally athymic mice were more susceptible to challenge with amastigotes of Leishmania donovani than were their thymus-intact littermates. This increased susceptibility correlated with a lack of Arthus and delayed-type responses when animals were skin tested with leishmanial antigen.

Animals↗
PubMed1978

Contact sensitivity responses in mice infected with Trypanosoma cruzi.

Mechanisms of depression of contact sensitivity responses in C57BL/10 mice infected with Trypanosoma cruzi were studied. Cellular involvement during sensitization with oxazolone was investigated in mice acutely infected with T. cruzi. Contact sensitivity was not expressed in mice during the latter stages of the acute infection. Spleen cells from sensitized, infected mice which were unable to respond to oxazolone could confer contact sensitivity upon normal syngenic mice as effectively as spleen cells from uninfected, sensitized donors. The ability of mice infected with T. cruzi to respond to an eliciting dose of oxazolone was significantly improved when macrophages from normal syngenic donors were administered to them at the time of skin test. When either normal or infected mice were used as recipients of lymphocytes from sensitized donors, the normal mice responded significantly better than did infected mice after administration of an eliciting dose of oxazolone. An increase in pyroninophilic cells was observed in draining lymph nodes after application of a sensitizing dose of oxaxolone to the ears of either normal or acutely infected mice. These results indicate that suppression of contact sensitivity during acute T. cruzi infection is directed toward the efferent arm rather than the afferent arm of the response.

Animals↗
PubMed1977

Suppression of cell-mediated immunity in experimental Chagas' disease.

The effect of acute infection with the Tulahuén strain of Trypanosoma cruzi on the cellular immune response in Swiss mice was studied. Mice were immunized with either Freund's complete adjuvant or oxazolone, a skin sensitizing agent, and subsequently skin-tested with either BCG protoplasm or oxazolone to detect delayed hypersensitivity. Depression of the response to these antigens was observed in infected mice during the stage of marked parasitemia. Mice which were responsive to oxazolone before infection lost their ability to respond as the infection progressed. When immunized with live attenuated T. cruzi before infection with virulent organisms, mice developed a greater than normal sensitivity to oxazolone and survived infection. These experiments do not conclude whether immunosuppression due to infection with T. cruzi is directed toward induction or expression of the cell-mediated immune response to the antigens employed.

Animals↗