Biomedical subjects

Deborah A Yurgelun-Todd

Publications and source records attributed to Deborah A Yurgelun-Todd.

At least 19 recordsLinked to original sources

PubMed2006

Reduced amygdala volumes in first-episode bipolar disorder and correlation with cerebral white matter.

BACKGROUND: Previous magnetic resonance imaging (MRI) findings on amygdala volume abnormalities in bipolar disorder have been inconsistent, which may partly reflect clinical heterogeneity. It is unclear whether amygdala abnormalities are present early in the course of illness and/or are the consequence of disease progression. METHODS: Twenty patients with first-episode bipolar disorder and 23 matched healthy comparison subjects were included. Magnetic resonance images were used to measure amygdala volumes, as well as whole brain measures of gray and white matter volume. RESULTS: First-episode bipolar patients had significant reductions in amygdala volume relative to healthy subjects in an analysis of covariance that accounted for the effects of age, sex, and whole brain volume. First-episode patients also showed a trend reduction in cerebral white matter volume, and there was a significant correlation between cerebral white matter volume and total amygdala volume in patients but not control subjects. CONCLUSIONS: These findings indicate that amygdala volume deficits are present early in the course of bipolar disorder and may occur within a neuroanatomical context of reduced cerebral white matter. Additional research should examine whether the nature of regional white matter deficits, particularly in frontal-temporal tracts, may help parse the pathophysiology of amygdala volume abnormalities in bipolar disorder.

Adult↗

PubMed2006

Fear-related activity in the prefrontal cortex increases with age during adolescence: a preliminary fMRI study.

An emerging theory of adolescent development suggests that brain maturation involves a progressive "frontalization" of function whereby the prefrontal cortex gradually assumes primary responsibility for many of the cognitive processes initially performed by more primitive subcortical and limbic structures. To test the hypothesis of developmental frontalization in emotional processing, we analyzed the correlation between age and prefrontal cortex activity in a sample of 16 healthy adolescents (nine boys; seven girls), ranging in age from 8 to 15 years, as they viewed images of fearful and happy faces while undergoing functional magnetic resonance imaging (fMRI). During fear perception, age was significantly positively correlated with greater functional activity within the prefrontal cortex, whereas no significant relationship was evident between age and activity in the amygdala. Consistent with previous gender-related findings, age was significantly correlated with bilateral prefrontal activity for the sample of females, but was only significantly related to right prefrontal activity for the males. In contrast, similar age-related correlations were not evident during the perception of happy faces. These results suggest that the maturation of threat-related emotional processing during adolescence is related to the progressive acquisition of greater functional activity within the prefrontal cortex. The hypothesis of age related decreases in amygdala activity was not supported, but may have been due to low signal-to-noise and inadequate power in the present sample to resolve subtle changes in this small structure.

Adolescent↗

PubMed2006

Recognition of happy facial affect in panic disorder: an fMRI study.

BACKGROUND: This study investigated activation of the anterior cingulate cortex (ACC) and amygdala during the presentation of happy facial affect images in patients with panic disorder (PD) as measured by blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). METHODS: Eight patients with PD and eight sex-matched controls were recruited for the study. Scanning was performed on a general electric (GE) Signa 1.5T scanner retrofitted with a whole body echo planar coil. Using a quadrature head coil, echo planar images and high-resolution MR images were acquired. RESULTS: After covarying for age, examination of group differences revealed greater ACC activation bilaterally in patients with PD compared to controls in response to happy faces. However, there were no differences in amygdala activation between the groups. These findings contrasted with regional brain activation in response to neutral faces where there were was also greater bilateral ACC activation in the PD group, but only 44 ACC voxels showed significant increases as opposed to 509 voxels for the happy condition. There were no between group differences in activation in the amygdala. CONCLUSION: This is the first fMRI study to our knowledge that demonstrates ACC abnormalities in response to happy facial affect recognition in PD.

Adult↗

PubMed2006

fMRI of fearful facial affect recognition in panic disorder: the cingulate gyrus-amygdala connection.

BACKGROUND: This study investigated cingulate cortex (CC) and amygdala response to fearful facial affect recognition in patients with panic disorder (PD) as measured by BOLD fMRI during the presentation of static facial images. METHODS: Eight patients with PD and eight controls were studied. Scanning was performed on a GE Signa 1.5-T scanner. Echo planar and high-resolution MR images were acquired. RESULTS: Controls produced greater CC activation compared to patients with PD in response to fearful faces. Furthermore, patients with PD produced less amygdala activation than controls in response to fearful faces. During the neutral face condition, overall activation for the CC was significantly greater in PD patients although anterior cingulate cortex (ACC) activation was not as markedly different between both groups. There were no between group differences in amygdala activation on exposure to the neutral face. Only left CC activation was significantly correlated negatively with HAM-A in PD patients in the fearful facial affect condition. LIMITATIONS: Although comparable to similar studies, the sample size is small enough to warrant further investigation. Also, the effects of medication need to be considered when interpreting these results. CONCLUSIONS: Patients with PD activate the ACC and amygdala significantly less than controls when asked to identify fearful facial affect during fMRI. The higher the anxiety, the lower the left CC activation. Thus, chronic hyperarousal in PD may diminish attentional resources and emotional response reflected in reduced ACC and amygdala activation. Even if these are medication effects, the differences from controls are clinically relevant.

Adult↗

PubMed2006

Sex differences in the relationship between white matter microstructure and impulsivity in adolescents.

Rapid maturational brain changes occur during adolescence--a time associated with risk-taking behaviors and improvements in cognition. The present study examined the relationship between white matter (WM) microstructure, impulsive behavior and response inhibition in female and male adolescents. Twenty-one healthy adolescents underwent diffusion tensor imaging using a 3.0-T magnetic resonance imaging system. Impulse control was assessed using the Bar-On Emotional Quotient Inventory, Youth Version. Response inhibition was assessed using the Stroop Color-Word Interference Test. Fractional anisotropy (FA), a measure of WM coherence, and trace, a measure of overall diffusivity, were determined from voxels manually placed in the midline and in the left and right forward-projecting arms of the genu and the splenium of the corpus callosum. Sex-specific differences were observed for the relationship between FA and impulsive behavior in the right anterior callosum for males and in the splenium for females. Males, compared to females, displayed significantly higher FA in the left WM region. Although trace was not associated with impulse control, trace in the genu (for females) and splenium (males and females) was associated with Stroop performance. Regional differences in trace also were evident, with lower values in the splenium observed than in all other regions. Although the latter significantly improved with age, no sex differences in impulse control or in Stroop performance were detected. The present findings provide supporting evidence for sex-related differences in the development of WM microstructure during adolescence. These data further suggest a neurobiological mechanism underlying some of the emotional and cognitive changes commonly observed in males versus females during the adolescent period.

Adolescent↗

PubMed2006

Ventromedial prefrontal activity correlates with depressed mood in adolescent children.

In adults, the medial prefrontal cortex and anterior cingulate gyrus are preferentially activated during emotion-related processes, including normal sadness and pathological depression. It is not clear, however, whether similar regional activity is also characteristic of depressed mood during adolescence. We correlated whole brain activity during a fear face perception task with scores on the Beck Depression Inventory in 16 adolescents undergoing functional magnetic resonance imaging. After controlling for age, depressed mood scores correlated with increased activity within the ventromedial prefrontal cortex and rostral anterior cingulate gyrus, consistent with findings previously reported for sadness and depression in adults, suggesting that the neural substrates of depressed mood are established early in life and remain relatively consistent across development into adulthood.

Adolescent↗

PubMed2006

Affect modulates appetite-related brain activity to images of food.

OBJECTIVE: We examined whether affect ratings predicted regional cerebral responses to high and low-calorie foods. METHOD: Thirteen normal-weight adult women viewed photographs of high and low-calorie foods while undergoing functional magnetic resonance imaging (fMRI). Regression analysis was used to predict regional activation from positive and negative affect scores. RESULTS: Positive and negative affect had different effects on several important appetite-related regions depending on the calorie content of the food images. When viewing high-calorie foods, positive affect was associated with increased activity in satiety-related regions of the lateral orbitofrontal cortex, but when viewing low-calorie foods, positive affect was associated with increased activity in hunger-related regions including the medial orbitofrontal and insular cortex. The opposite pattern of activity was observed for negative affect. CONCLUSION: These findings suggest a neurobiologic substrate that may be involved in the commonly reported increase in cravings for calorie-dense foods during heightened negative emotions.

Adult↗

PubMed2006

Functional magnetic resonance imaging studies in bipolar disorder.

Abnormalities in brain activation using functional magnetic resonance imaging (fMRI) during cognitive and emotional tasks have been identified in bipolar disorder patients, in frontal, subcortical and limbic regions. Several studies also indicate that mood state may be differentiated by lateralization of brain activation in fronto-limbic regions. The interpretation of fMRI studies in bipolar disorder is limited by the choice of regions of interest, medication effects, comorbidity, and task performance. These studies suggest that there is a complex alteration in regions important for neural networks underlying cognition and emotional processing in bipolar disorder. However, measuring changes in specific brain regions does not identify how these neural networks are affected. New analytical techniques of fMRI data are needed in order to resolve some of these issues and identify how changes in neural networks relate to cognitive and emotional processing in bipolar disorder.

Bipolar Disorder↗

PubMed2006

Methadone maintenance improves cognitive performance after two months of treatment.

Methadone maintenance (MM) has received little scientific attention regarding neurocognitive effects. The present study examined cognitive function in 17 opiate-dependent subjects at baseline and after 2 months of MM treatment. Subjects demonstrated significant improvements from baseline on measures of verbal learning and memory, visuospatial memory, and psychomotor speed and reduced frequency of drug use (Addiction Severity Index) relative to baseline, although the total percentage of urine samples positive for additional illicit substances was slightly increased. No effect of illicit drug use was observed when the sample was stratified by urine toxicology results, suggesting that improvements in cognition were not associated with additional illicit drug use. Results suggest that opiate-dependent subjects exhibit significant improvement in cognitive function after MM treatment. Future investigations are needed to confirm these findings.

Adult↗

PubMed2006

Altered regional blood volume in chronic cannabis smokers.

The quantitative measurement of cerebral perfusion is crucial for the study of both normal and impaired human brain function. Although cannabis is the most commonly abused illicit substance in the United States, its effects on cerebral blood volume (CBV) have not been fully examined. The objective of the present study was to examine differences in relative regional blood volume in focal regions of interest--including the frontal lobe, the temporal lobe, and the cerebellum--during a period of supervised abstinence from cannabis. Dynamic susceptibility contrast MRI data were collected on 12 current, long-term daily cannabis users between 6 and 36 hr after the subjects' last reported cannabis use. Resting-state CBV images were also acquired in 17 healthy comparison subjects. Data were acquired in the axial plane with a 1.5-Tesla GE Signa scanner following a bolus of gadolinium contrast agent. Cannabis users demonstrated significantly increased blood volumes in the right frontal area (p < .05), in the left temporal area (p < .005), and in the cerebellum (p < .005) relative to comparison subjects. Among the cannabis users, there were no significant correlations between regional blood volumes and either total lifetime episodes of smoking or urinary tetrahydrocannabinol concentrations. These findings have important implications for understanding the effects of chronic heavy cannabis use on brain function. It would be of interest to extend the investigation beyond 6-36 hr of abstinence from cannabis to determine whether increased CBV values persist for several weeks or eventually normalize.

Adult↗

PubMed2005

Prefrontal and temporal gray matter density decreases in opiate dependence.

RATIONALE: There have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects. OBJECTIVES: The objective of the current study is to explore gray matter density in opiate-dependent subjects. METHODS: Gray matter density in 63 opiate-dependent subjects and 46 age- and sex-matched healthy comparison subjects was compared using VBM. RESULTS: Relative to healthy comparison subjects, opiate-dependent subjects exhibited decreased gray matter density in bilateral prefrontal cortex [Brodmann areas (BA) 8, 9, 10, 11, and 47], bilateral insula (BA 13), bilateral superior temporal cortex (BA 21 and 38), left fusiform cortex (BA 37), and right uncus (BA 28). CONCLUSIONS: This study reports that opiate-dependent subjects have gray matter density decreases in prefrontal and temporal cortex, which may be associated with behavioral and neuropsychological dysfunction in opiate-dependent subjects.

Adult↗

PubMed2005

Social anxiety predicts amygdala activation in adolescents viewing fearful faces.

The amygdala is critically involved in the processing of anxiety in adults, but little is known about the neurogenesis of trait-anxiety during adolescence. We correlated amygdala activity during visual presentations of fearful and happy faces with scores on the Multidimensional Anxiety Scale for Children in 16 adolescents undergoing functional magnetic resonance imaging. During fear perception, amygdala activity positively correlated with several social dimensions of anxiety, including peer rejection, humiliation, performing in public, and being separated from loved ones, but was not correlated with most measured nonsocial dimensions of anxiety. Amygdala responses during happy face presentations correlated positively only with tension/restlessness. During adolescence, amygdala activity appears to be more strongly related to social/interpersonal than nonsocial dimensions of anxiety.

Adolescent↗

PubMed2005

Body mass predicts orbitofrontal activity during visual presentations of high-calorie foods.

Little is known about the relationship between weight status and reward-related brain activity in normal weight humans. We correlated orbitofrontal and anterior cingulate cortex activity as measured by functional magnetic resonance imaging with body mass index in 13 healthy, normal-weight adult women as they viewed images of high-calorie and low-calorie foods, and dining-related utensils. Body mass index correlated negatively with both cingulate and orbitofrontal activity during high-calorie viewing, negatively with orbitofrontal activity during low-calorie viewing, and positively with orbitofrontal activity during presentations of nonedible utensils. With greater body mass, activity was reduced in brain regions important for evaluating and modifying learned stimulus-reward associations, suggesting a relationship between weight status and responsiveness of the orbitofrontal cortex to rewarding food images.

Adult↗

PubMed2005

Activation in dorsolateral prefrontal cortex in response to maternal criticism and praise in recovered depressed and healthy control participants.

BACKGROUND: High family levels of expressed emotion reliably predict relapse in patients with schizophrenia and mood disorders; however, the neural mechanisms linking expressed emotion and relapse are unexplored. Dysfunctional activity in the dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of depression. Functional magnetic resonance imaging (fMRI) was used to assess focal activation changes in DLPFC in response to a novel psychosocial challenge stimulus developed from the expressed emotion construct. METHODS: Healthy control subjects and fully remitted unipolar depressed participants completed blood oxygen level-dependent fMRI while they heard their own mothers making critical and praising comments about them. RESULTS: Relative to control subjects, participants with a history of depression failed to activate DLPFC when they heard critical remarks. There were no differences between the two groups in their DLPFC responses to maternal praise. CONCLUSIONS: Even if fully well at the time of testing, participants with a known vulnerability to depression respond differently to the psychosocial challenge of being criticized. These findings might have implications for our understanding of vulnerability to depression and to depressive relapse.

Acoustic Stimulation↗

PubMed2005

Functional magnetic resonance imaging studies of schizophrenic patients during word production: effects of D-cycloserine.

The objective of the present study was to examine patterns of cortical activation underlying D-cycloserine's therapeutic efficacy in schizophrenic patients using functional magnetic resonance imaging (fMRI). We measured frontal and temporal lobe activation following a word fluency task in 12 subjects meeting DSM-IV criteria for schizophrenia at baseline and after 8 weeks of supervised treatment, using a double-blind, placebo-controlled design. Half of the patients received D-cycloserine (n = 6) as a supplement to their conventional neuroleptic treatment while the other half (n = 6) was augmented with placebo. Patients receiving D-cycloserine, but not placebo, demonstrated a significant increase in temporal lobe activation. This increased activation was significantly associated with a reduction in negative symptoms. These results suggest that the addition of D-cycloserine to conventional neuroleptics may improve negative symptoms through enhanced temporal lobe function.

Antipsychotic Agents↗

PubMed2005

Amygdala and hippocampus volumes in pediatric major depression.

BACKGROUND: The purpose of this study was to measure amygdala and hippocampus volumes in pediatric major depressive disorder (MDD) and to address the question of neuroanatomical continuity with adult-onset depression. METHODS: We studied 20 children and adolescents with MDD (17 female subjects) and 24 healthy comparison subjects (16 female subjects) using 1.5 Tesla magnetic resonance imaging. Group differences in left and right amygdala and hippocampus volumes were examined using repeated measures analyses of covariance, adjusting for age, gender, and whole brain volume. RESULTS: Depressed children had significant reductions of left and right amygdala volumes compared with healthy subjects. Hippocampus volumes did not differ between the groups. No significant correlations were found between amygdala volumes and depressive symptom severity, age at onset, or illness duration. CONCLUSIONS: Smaller amygdalas are present early in the course of pediatric depression and may predispose to the development of this disorder or perhaps more generally of childhood mood disorders. Future research should examine the longitudinal course and functional correlates of amygdala volume abnormalities in childhood-onset depression, including their possible moderation by gender.

Adolescent↗

PubMed2005

Developmental changes in the functional brain responses of adolescents to images of high and low-calorie foods.

We examined cerebral responses to visually presented food images in children and adolescents. Eight healthy normal-weight females (ages 9-15) underwent functional magnetic resonance imaging (fMRI) while viewing photographs of high- and low-calorie foods and dining utensils. In general, food images yielded significant activation within the inferior orbitofrontal cortex, hippocampus, and fusiform gyri. High calorie food images activated the left hippocampus and subgenual cingulate, and age correlated positively with activity within the orbitofrontal cortex but negatively with activity within the anterior cingulate gyrus. Low-calorie foods activated the fusiform gyrus and demonstrated age-related increases in the left superior temporal gyrus and anterior cingulate. Utensils activated the fusiform gyrus and showed age-related increases in the prefrontal cortex. Data were also compared statistically to a sample of adults exposed to the same stimulus conditions. Findings support a developmental model of adolescent maturation whereby age-related changes in cerebral functioning develop from lower-order sensory processing toward higher-order processing of stimuli via prefrontal cortical systems involved in reward anticipation, self-monitoring, and behavioral inhibition.

Adolescent↗

PubMed2005

Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation.

Neuropsychological investigations of substance abusers have reported impairments on tasks mediated by the frontal executive system, including functions associated with behavioral inhibition and decision making. The higher order or executive components which are involved in decision making include selective attention and short term storage of information, inhibition of response to irrelevant information, initiation of response to relevant information, self-monitoring of performance, and changing internal and external contingencies in order to "stay the course" towards the ultimate goal. Given the hypothesized role of frontal systems in decision making and the previous evidence that executive dysfunctions and structural brain changes exist in subjects who use illicit drugs, we applied fMRI and diffusion tensor imaging (DTI) techniques in a pilot investigation of heavy cannabis smokers and matched control subjects while performing a modification of the classic Stroop task. Marijuana smokers demonstrated significantly lower anterior cingulate activity in focal areas of the anterior cingulate cortex and higher midcingulate activity relative to controls, although both groups were able to perform the task within normal limits. Normal controls also demonstrated increased activity within the right dorsolateral prefrontal cortex (DLPFC) during the interference condition, while marijuana smokers demonstrated a more diffuse, bilateral pattern of DLPFC activation. Similarly, although both groups performed the task well, marijuana smokers made more errors of commission than controls during the interference condition, which were associated with different brain regions than control subjects. These findings suggest that marijuana smokers exhibit different patterns of BOLD response and error response during the Stroop interference condition compared to normal controls despite similar task performance. Furthermore, DTI measures in frontal regions, which include the genu and splenium of the corpus callosum and bilateral anterior cingulate white matter regions, showed no between group differences in fractional anisotropy (FA), a measure of directional coherence within white matter fiber tracts, but a notable increase in trace, a measure of overall isotropic diffusivity in marijuana smokers compared to controls. Overall, results from the present study indicate significant differences in the magnitude and pattern of signal intensity change within the anterior cingulate and the DLPFC during the Stroop interference subtest in chronic marijuana smokers compared to normal controls. Furthermore, although chronic marijuana smokers were able to perform the task reasonably well, the functional activation findings suggest they utilize different cortical processes from the control subjects in order to do so. Findings from this study are consistent with the notion that substance abusers demonstrate evidence of altered frontal neural function during the performance of tasks that involve inhibition and performance monitoring, which may affect the ability to make decisions.

Adolescent↗