Faculty Bibliography

Emotion regulation can be achieved in various ways, but few studies have evaluated the extent to which the neurocognitive substrates of these distinct operations overlap. In the study reported here, functional magnetic resonance imaging (fMRI) was used to measure activity in the amygdala and prefrontal cortex of 10 participants who completed two independent tasks of emotion regulation-reappraisal, measuring intentional emotion regulation, and affect labeling, measuring incidental emotion regulation-with the objective of identifying potential overlap in the neural substrates underlying each task. Analyses focused on a priori regions of interest in the amygdala and inferior frontal gyrus (IFG). For both tasks, fMRI showed decreased amygdala activation during emotion regulation compared with emotion conditions. During reappraisal, this decrease in amygdala activation was accompanied by a proportional decrease in emotional intensity ratings; during affect labeling, the decrease in amygdala activation correlated with self-reported aggression. Importantly, across participants, the magnitude of decrease in amygdala activation during reappraisal correlated with the magnitude of decrease during affect labeling, even though the tasks were administered on separate days, and values indexing amygdala activation during each task were extracted independently of one another. In addition, IFG-amygdala connectivity, assessed via psychophysiological interaction analysis, overlapped between tasks in two regions within the right IFG. The results suggest that the two tasks recruit overlapping regions of prefrontal cortex, resulting in similar reductions in amygdala activation, regardless of the strategy employed. Intentional and incidental forms of emotion regulation, despite their phenomenological differences, may therefore converge on a common neurocognitive pathway.

Psychological and neurocognitive studies have suggested that different kinds of self-control may share a common psychobiological component. If this is true, performance in affective and nonaffective inhibitory control tasks in the same individuals should be correlated and should rely upon integrity of this region. To test this hypothesis, we acquired high-resolution magnetic resonance images from 44 healthy and 43 methamphetamine-dependent subjects. Individuals with methamphetamine dependence were tested because of prior findings that they suffer inhibitory control deficits. Gray matter structure of the inferior frontal gyrus was assessed using voxel-based morphometry. Subjects participated in tests of motor and affective inhibitory control (stop-signal task and emotion reappraisal task, respectively); and methamphetamine-dependent subjects provided self-reports of their craving for methamphetamine. Performance levels on the two inhibitory control tasks were correlated with one another and with gray matter intensity in the right pars opercularis region of the inferior frontal gyrus in healthy subjects. Gray matter intensity of this region was also correlated with methamphetamine craving. Compared with healthy subjects, methamphetamine-dependent subjects exhibited lower gray matter intensity in this region, worse motor inhibitory control, and less success in affect regulation. These findings suggest that self-control in different psychological domains involves a common substrate in the right pars opercularis, and that successful self-control depends on integrity of this substrate.

A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity.

AIMS: This review aims to present and interpret evidence that methamphetamine dependence is associated with disorder of brain function that is required for top-down control of behavior. APPROACH: Presented here are findings from brain imaging studies of human research participants with histories of chronic methamphetamine abuse in the context of functional consequences and implications for treatment of their dependence on methamphetamine. FINDINGS: Brain imaging studies have revealed differences in the brains of research participants who have used methamphetamine chronically and then abstained from taking the drug, compared with healthy control subjects. These abnormalities are prominent in cortical and limbic systems, and include deficits in markers of dopaminergic and serotonergic neurotransmitter systems, differences in glucose metabolism and deficits in gray matter. These abnormalities accompany cognitive deficits, including evidence of impaired inhibitory control. CONCLUSION: Cortical deficits in abstinent methamphetamine abusers can affect a wide range of functions that can be important for success in maintaining drug abstinence. These include but are not limited to modulation of responses to environmental stimuli as well as internal triggers that can lead to craving and relapse. Potential therapies may combine behavioral approaches with medications that can improve cognitive control.

The administration of ethanol on a chronic intermittent regimen (CIE) involving multiple withdrawal episodes is a model for ethanol dependence. After CIE, rats exhibited reduced seizure threshold, increased anxiety, tolerance to GABAergic sedative-hypnotic drugs, and changes in GABA(A) receptor function and subunit composition in hippocampus. Previous studies have shown that acute and chronic ethanol may induce changes in the levels of the neurosteroid 3alpha-hydroxysteroid-5alpha-pregnan-20-one (3alpha, 5alpha-THP) in the brain. Therefore, the current study analyses the correlation between chronic intermittent ethanol effects on the level of 3alpha, 5alpha-THP in hippocampus of CIE rats and the behavioral changes in sensitivity to neurosteroids. After CIE, the levels for 3alpha, 5alpha-THP were significantly reduced in hippocampus of rats. The mRNA levels for the enzymes 5alpha-reductase and 3alpha-HSD in hippocampus were also reduced. In vivo, (in contrast to a tolerance to the hypnotic effect of steroids), CIE rats showed increased sensitivity to the anticonvulsant and to the anxiolytic effect of the steroid alphaxalone. Perhaps, this is a response to lowered levels of endogenous neuroactive steroids. CIE rats also showed impairment of hippocampus-dependent memory function. These results suggest that changes in neurosteroids level and in vivo sensitivity to these compounds are involved in the development of ethanol dependence in the CIE model.

Topiramate, a novel anticonvulsant drug, has CNS depressant activity including enhancement of GABAergic inhibitory synaptic transmission. Drugs of this pharmacological spectrum might have utility in assuaging drug addiction. This study analyzes the ability of TPM to reduce withdrawal signs in the kindling model of ethanol dependence: chronic intermittent ethanol (CIE) rats. After CIE, persistent withdrawal signs are shown by an increased seizure susceptibility to the convulsant drug pentylenetetrazol and increased anxiety measured on the elevated plus-maze. Topiramate increased significantly the PTZ seizure threshold in CIE but not in control rats. On the elevated plus-maze, Topiramate was markedly more effective in CIE rats than in controls. Topiramate may have a therapeutic efficacy in treating alcohol withdrawal symptoms.