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Biomedical subjects

Staci A Gruber

Publications and source records attributed to Staci A Gruber.

15 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Decreased activation of the anterior cingulate in bipolar patients: an fMRI study.

BACKGROUND: Previous neuroimaging investigations of patients with bipolar disorder have reported abnormalities of the frontal subcortical network. The role of the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) in bipolar disorder are not clear, although both regions have been shown to be components of a neural network which plays a critical role in the completion of tasks requiring self-monitoring and inhibition, functions often noted to be altered in bipolar patients. fMRI studies have helped clarify the role of specific subdivisions of the ACC and the DLPFC during the performance of cognitive challenges, including the Stroop color word test. To date, studies that have examined ACC function in bipolar patients have not differentiated subregions within this area, nor have they examined changes in these subregions in relation with DLPFC activation. METHODS: To help clarify the specific roles of these regions in bipolar patients, we examined stable patients and control subjects during performance of the Stroop test using BOLD fMRI techniques. We hypothesized that bipolar patients would demonstrate reduced activation of two subdivisions of the ACC (AAA and VOA), as well as altered activation of the DLPFC, during the interference condition. RESULTS: Results indicate that relative to controls, bipolar patients demonstrated significantly reduced signal intensity within the right AAA subdivision (p=0.011), which accompanied an increase in the DLPFC (p=0.049) during the task. LIMITATIONS: The study sample was somewhat small (11 patients, 10 controls) which limits the generalizability of the study findings, however, the patient sample consisted of well-diagnosed, stable, chronic individuals with bipolar disorder and the sample size provided enough power to detect between-group differences. CONCLUSIONS: These findings suggest differential processing strategies of bipolar patients and support the theory of altered frontal systems in these patients during the performance of cognitive tasks.

Adult↗

Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study.

RATIONALE: Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users. However, little is known about the effects of cannabis on brain activity. OBJECTIVE: We assessed brain function among recent heavy cannabis users while they performed a working memory task. METHODS: Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users, 6-36 h after last use, and in 10 control subjects while they performed a spatial working memory task. Regional brain activation was analyzed and compared using statistical parametric mapping techniques. RESULTS: Compared with controls, cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks (such as prefrontal cortex and anterior cingulate). Users also recruited additional regions not typically used for spatial working memory (such as regions in the basal ganglia). These findings remained essentially unchanged when re-analyzed using subjects' ages as a covariate. Brain activation showed little or no significant correlation with subjects' years of education, verbal IQ, lifetime episodes of cannabis use, or urinary cannabinoid levels at the time of scanning. CONCLUSIONS: Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task. This observation suggests that recent cannabis users may experience subtle neurophysiological deficits, and that they compensate for these deficits by "working harder"-calling upon additional brain regions to meet the demands of the task.

Adult↗

Frontal lobe GABA levels in cocaine dependence: a two-dimensional, J-resolved magnetic resonance spectroscopy study.

Non-invasive measures of brain gamma-aminobutyric acid (GABA) concentrations may be especially useful in the identification of cocaine-related changes in brain chemistry that can be used to guide the development of future treatments for cocaine-dependent persons. This study assessed whether brain GABA levels in cocaine-dependent subjects with and without an alcohol disorder differ from GABA levels in healthy comparison subjects. Two-dimensional, proton magnetic resonance spectroscopy was used to determine GABA levels in the left prefrontal lobe of cocaine-dependent subjects (N=35) recruited from a National Institute on Drug Abuse (NIDA)-sponsored treatment trial of cocaine dependence and a comparison group (N=20). At treatment baseline, mean GABA concentrations were 0.93+/-0.27 mM/kg in cocaine-dependent subjects and 1.32+/-0.44 mM/kg in the comparison sample (t [d.f.=53]=3.65, P<0.001). Cocaine-dependent subjects with a history of a co-morbid alcohol disorder (N=23) had significantly lower baseline GABA levels (0.87 mM/kg) (t [d.f.=41]=4.31, P<0.001) than the comparison group. However, cocaine-dependent subjects without an alcohol disorder (N=12) also had lower GABA levels (1.04 mM/kg) than the comparison subjects (t [d.f.=30]=2.09, P=0.045), suggesting that cocaine dependence alone can decrease GABA levels.

Adult↗

Functional magnetic resonance imaging in schizophrenia: cortical response to motor stimulation.

Previous functional magnetic resonance imaging (fMRI) studies suggest that motor system abnormalities are present in schizophrenia. However, these studies have often produced conflicting or ambiguous findings. The purpose of this study was to ascertain whether activation differences could be identified in stable schizophrenic patients on the basis of BOLD measures in two motor regions, the primary motor cortex, Brodmann area 4 (BA4) and the premotor and supplementary motor area, Brodmann area 6 (BA6). Twenty-one schizophrenic patients and 21 healthy control subjects were studied with BOLD fMRI methods during a sequential finger tapping task. Statistical parametric maps were generated for each subject, and anatomic regions were automatically defined using an anatomic atlas. Compared with controls, the schizophrenic patients showed a significant reduction in contralateral activation for both BA4 and BA6 (P<0.001), and in ipsilateral activation in BA4 (P=0.007) and BA6 (P=0.002). In healthy controls, the coactivation in the ipsilateral cortex is reduced in comparison with the contralateral cortex for right and left handed tasks. In BA4, this reduction is significant for right (P=0.007) and left (P=0.003) finger tapping. Similar results were obtained for BA6. Further analyses are necessary to evaluate the activation in other motor system regions.

Adult↗

Cerebellar blood volume in bipolar patients correlates with medication.

BACKGROUND: Cerebellar abnormalities, including decreased tissue volume, have been implicated in the pathophysiology of bipolar disorder. Relatively little research has focused on blood flow in the cerebellum of patients with bipolar disorder. Furthermore, the significance of metabolic changes in the brains of psychiatric patients may be confounded by the effects of various pharmacotherapies. Having previously found differences in cerebellar blood volume in patients with bipolar disorder compared to healthy control subjects, this study examined whether some variability in the patient population may be an effect of medication. METHODS: In this study, we have examined the association between medication status and cerebellar blood volume. Thirteen healthy comparison subjects and 21 bipolar patients underwent dynamic susceptibility contrast magnetic resonance imaging. Nine cerebellar regions were identified, and the absolute cerebellar blood volume data from each was compared to medication status measures. RESULTS: Patients on conventional antipsychotics had the lowest mean absolute blood volume measures for all cerebellar regions, whereas those on atypical antipsychotics had the highest blood volume measures. Comparison subjects had cerebellar blood volume measures in the middle, with results closer to subjects in the atypical group. CONCLUSIONS: This evidence suggests that antipsychotic treatment may influence cerebellar blood volume. This effect will be important in considering imaging studies on medicated patients with bipolar disorder and may suggest novel pathways by which these medications affect their changes.

Adolescent↗

Stroop performance in normal control subjects: an fMRI study.

In an attempt to clarify regional signal intensity changes, which may accompany the performance of the Stroop Color-Word task, healthy subjects were imaged using the fMRI BOLD technique while performing a modified version of the task. Both the AAA and VOA subdivisions of the anterior cingulate cortex were significantly activated during the interference condition; however, only the signal intensity change within the VOA correlated with task performance. Additionally, signal intensity change was significantly increased in the VOA subdivision of the cingulate cortex when controlling for signal intensity change present during the performance of a color naming task. This study extends previous findings by demonstrating that in healthy adults, a subdivision of the cingulate cortex is specifically associated with the cognitive demands present in the interference condition.

Adult↗