Showing papers by "Edythe D. London published in 2007"

Frontoparietal cortical activity of methamphetamine-dependent and comparison subjects performing a delay discounting task.

Abstract: Relative to individuals who do not have addictive disorders, drug abusers exhibit greater devaluation of rewards as a function of their delay ("delay discounting"). The present study sought to extend this finding to methamphetamine (MA) abusers and to help understand its neural basis. MA abusers (n = 12) and control subjects who did not use illicit drugs (n = 17) participated in tests of delay discounting with hypothetical money rewards. We then used a derived estimate of each individual's delay discounting to generate a functional magnetic resonance imaging probe task consisting of three conditions: "hard choices," requiring selections between "smaller, sooner" and "larger, later" alternatives that were similarly valued given the individual's delay discounting; "easy choices," in which alternatives differed dramatically in value; and a "no choice" control condition. MA abusers exhibited more delay discounting than control subjects (P no choice" contrast revealed significant effects in the ventrolateral prefrontal cortex, dorsolateral prefrontal cortex (DLPFC), dorsal anterior cingulate cortex, and areas surrounding the intraparietal sulcus (IPS). With group comparisons limited to these clusters, the "hard choice > easy choice" contrast indicated significant group differences in task-related activity within the left DLPFC and right IPS; qualitatively similar nonsignificant effects were present in the other clusters tested. Whereas control subjects showed less recruitment associated with easy than with hard choices, MA abusers generally did not. Correlational analysis did not indicate a relationship between this anomaly in frontoparietal recruitment and greater degree of delay discounting exhibited by MA abusers. Therefore, while apparent inefficiency of cortical processing related to decision-making in MA abusers may contribute to the neural basis of enhanced delay discounting by this population, other factors remain to be identified.

Leptin replacement alters brain response to food cues in genetically leptin-deficient adults

Abstract: 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.

Corticolimbic dysregulation and chronic methamphetamine abuse.

Abstract: 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.

Intramuscular testosterone treatment in elderly men: evidence of memory decline and altered brain function.

Abstract: Context: Recent clinical trials of im testosterone in eugonadal men suggest positive effects on verbal memory, but other studies find no effect. Objective: Our objective was to determine whether supraphysiological testosterone influences verbal memory and brain function during a verbal memory task in healthy eugonadal older men. Patients, Design, and Setting: Fifteen cognitively normal men, aged 66–86 yr, participated in a randomized, double-blind, placebo-controlled crossover trial involving 9 months of participation per participant at a hospital-based research facility. Intervention: We used testosterone enanthate (200 mg im every other week for 90 d) crossed over with placebo (sesame oil vehicle im) with a 90-d washout between treatments. Main Outcome Measures: Performance was assessed on a standardized verbal memory test, and brain activity (relative glucose metabolic rates) in medial temporal and frontal regions was measured with positron emission tomography during a verbal memory task. Results: Trea...

Effects of cigarette smoking and abstinence on Stroop task performance.

Abstract: Rationale Smokers report enhanced concentration after cigarette smoking and difficulty concentrating when abstinent from smoking. These perceived effects may contribute to smoking cessation failures, and if so, clarification of their cognitive bases could inform treatment strategies. Selective attention may be important in this regard, but earlier literature presents inconsistent findings on how smoking abstinence and resumption of smoking influence this cognitive function.