Staci A. Gruber

Functional Magnetic Resonance Imaging of Facial Affect Recognition in Children and Adolescents

OBJECTIVE To examine further the role of the amygdala in the recognition of facial expression in adolescents. METHOD Twelve healthy adolescents were studied using functional magnetic resonance imaging technology during a task of facial affect recognition and a visual control task. RESULTS All subjects demonstrated a significant increase in signal intensity in the amygdala for the facial expression recognition task. CONCLUSIONS The data are consistent with previous work in healthy adult subjects implicating the amygdala as essential for the recognition of fearful facial expression.

Estrogen therapy selectively enhances prefrontal cognitive processes: A randomized, double-blind, placebo-controlled study with functional magnetic resonance imaging in perimenopausal and recently postmenopausal women

Objective: Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older postmenopausal women, suggesting a window of opportunity when ET is most beneficial. Cognitive improvement in younger postmenopausal women has been attributed to ETs influence on hot flushes and sleep, but empiric examination of the mediating role of menopause symptoms versus direct effects of ET on the brain is limited. Design: In a double-blind trial, 52 women were randomly assigned to estradiol 0.05 mg/day (n = 26) or placebo transdermal patches (n = 26) for 12 weeks. Women completed tests of memory, learning, and executive functioning, and hot flush and sleep assessments at baseline and study end. A subset of women (five ET treated, six placebo treated) also underwent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. Results: Nondepressed perimenopausal and postmenopausal women were studied. The majority had hot flushes and sleep impairment. Compared with placebo, ET selectively reduced errors of perseveration during verbal recall (P = 0.03), a frontal system-mediated function, but did not influence other cognitive processes. Women with baseline hot flushes had greater cognitive benefit with ET (P < 0.05). Cognitive benefit was not associated with sleep problems or its improvement. Measures of fMRI BOLD activation during tests of verbal and spatial working memory showed significant increases in frontal system activity with ET (P < 0.001). Conclusions: Estrogen therapy selectively improves executive functioning as demonstrated by reduced perseverative errors and prefrontal cortex activation during verbal recall tasks. Cognitive improvement with ET is associated with hot flushes, but not with sleep, suggesting that ET has a direct central nervous system effect, rather than an indirect effect mediated through improvement of sleep.

Performance on the Stroop predicts treatment compliance in cocaine-dependent individuals

Treatment dropout is a problem of great prevalence and stands as an obstacle to recovery in cocaine-dependent (CD) individuals. Treatment attrition in CD individuals may result from impairments in cognitive control, which can be reliably measured by the Stroop color–word interference task. The present analyses contrasted baseline performance on the color-naming, word-reading, and interference subtests of the Stroop task in CD subjects who completed a cocaine treatment trial (completers: N=50) and those who dropped out of the trial before completion (non-completers: N=24). A logistic regression analysis was used to predict trial completion using three models with the following variables: the Stroop task subscale scores (Stroop model); the Hamilton depression rating scale (HDRS) scores (HDRS model); and both the Stroop task subscale scores and HDRS scores (Stroop and HDRS model). Each model was able to significantly predict group membership (completers vs non-completers) better than a model based on a simple constant (HDRS model p=0.02, Stroop model p=0.006, and Stroop and HDRS model p=0.003). Models using the Stroop preformed better than the HDRS model. These findings suggest that the Stroop task can be used to identify cocaine-dependent subjects at risk for treatment dropout. The Stroop task is a widely available, reliable, and valid instrument that can be easily employed to identify and tailor interventions of at risk individuals in the hope of improving treatment compliance.

Neuropsychological Consequences of Opiate Use

Approximately 3.7 million individuals have used heroin and other opiate substances in their lifetime. Despite increasing knowledge of the effects of heroin, it remains the most abused opiate and use among adults has recently increased. The empirical literature examining the neurocognitive effects of acute and chronic opioid use remains limited; however, findings to date suggest that the use of opiates has both acute and long-term effects on cognitive performance. Neuropsychological data indicate deficits in attention, concentration, recall, visuospatial skills and psychomotor speed with both acute and chronic opioid use. The long-term effects of opiate use appear to have the greatest impact on executive functions, including the ability to shift cognitive set and inhibit inappropriate response tendencies. Factors that contribute to addiction and recovery are also discussed, as it is difficult to disentangle the effects of opiate use on cognitive performance from other factors that may affect neurobehavioral measures.

Age of onset of marijuana use and executive function.

Marijuana (MJ) remains the most widely abused illicit substance in the United States, and in recent years, a decline in perceived risk of MJ use has been accompanied by a simultaneous increase in rates of use among adolescents. In this study, the authors hypothesized that chronic MJ smokers would perform cognitive tasks, specifically those that require executive function, more poorly than control subjects and that individuals who started smoking MJ regularly prior to age 16 (early onset) would have more difficulty than those who started after age 16 (late onset). Thirty-four chronic, heavy MJ smokers separated into early and late onset groups, and 28 non-MJ smoking controls completed a battery of neurocognitive measures. As hypothesized, MJ smokers performed more poorly than controls on several measures of executive function. Age of onset analyses revealed that these between-group differences were largely attributed to the early onset group, who were also shown to smoke twice as often and nearly 3 times as much MJ per week relative to the late onset smokers. Age of onset, frequency, and magnitude of MJ use were all shown to impact cognitive performance. Findings suggest that earlier MJ onset is related to poorer cognitive function and increased frequency and magnitude of MJ use relative to later MJ onset. Exposure to MJ during a period of neurodevelopmental vulnerability, such as adolescence, may result in altered brain development and enduring neuropsychological changes.

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.

Assessment of 31P relaxation times in the human calf muscle: A comparison between 3 T and 7 T in vivo

Phosphorus (31P) T1 and T2 relaxation times in the resting human calf muscle were assessed by interleaved, surface coil localized inversion recovery and frequency‐selective spin‐echo at 3 and 7 T. The obtained T1 (mean ± SD) decreased significantly (P < 0.05) from 3 to 7 T for phosphomonoesters (PME) (8.1 ± 1.7 s to 3.1 ± 0.9 s), phosphodiesters (PDE) (8.6 ± 1.2 s to 6.0 ± 1.1 s), phosphocreatine (PCr) (6.7 ± 0.4 s to 4.0 ± 0.2 s), γ‐NTP (nucleotide triphosphate) (5.5 ± 0.4 s to 3.3 ± 0.2 s), α‐NTP (3.4 ± 0.3 s to 1.8 ± 0.1 s), and β‐NTP (3.9 ± 0.4 s to 1.8 ± 0.1 s), but not for inorganic phosphate (Pi) (6.9 ± 0.6 s to 6.3 ± 1.0 s). The decrease in T2 was significant for Pi (153 ± 9 ms to 109 ± 17 ms), PDE (414 ± 128 ms to 314 ± 35 ms), PCr (354 ± 16 ms to 217 ± 14 ms), and γ‐NTP (61.9 ± 8.6 ms to 29.0 ± 3.3 ms). This decrease in T1 with increasing field strength of up to 62% can be explained by the increasing influence of chemical shift anisotropy on relaxation mechanisms and may allow shorter measurements at higher field strengths or up to 62% additional signal‐to‐noise ratio (SNR) per unit time. The fully relaxed SNR increased by +96%, while the linewidth increased from 6.5 ± 1.2 Hz to 11.2 ± 1.9 Hz or +72%. At 7 T 31P‐MRS in the human calf muscle offers more than twice as much SNR per unit time in reduced measurement time compared to 3 T. This will facilitate in vivo 31P‐MRS of the human muscle at 7 T. Magn Reson Med, 2009.

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.

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.

In vivo quantification of intracerebral GABA by single-voxel 1H-MRS—How reproducible are the results?

Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H(2)O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H(2)O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H(2)O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr approximately 10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.