Objective-Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans.Method-Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions.Results-During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the nondrug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex).Conclusions-These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.Craving for a drug is a cardinal feature of addictive disorders and is clinically significant because of its potential to trigger drug use and relapse (1). The cocaine epidemic in the United States has prompted an intensive, largely unsuccessful search for medications to treat cocaine craving (2,3). This search has likely been complicated by a heterogeneous target: drug desire that emerges during cocaine cessation (4) may well have a different brain substrate than desire induced by cocaine itself (5) and the cues that signal it (6). Noninvasive brain imaging studies have recently begun to examine the brain substrates of both withdrawal-based craving (7,8) and cue-induced craving (9-11) in humans. We present here a hypothesis-guided imaging study of cue-induced cocaine craving in which we used evocative video cues from our prior work, which measured peripheral and subjective correlates of that state (6,(12)(13)(14).Human cocaine users often experience profound desire for the drug when they encounter cues (people, places, paraphernalia, etc.) associated with cocaine (6,15). Cue-induced cocaine craving is sometimes accompanied by a number of signs and symptoms similar to the effects Address reprint requests to Dr. Childress, Addiction Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, 3900 Chestnut St., Philadelphia, PA 19104; childress@research.trc.upenn.edu.. Data presented in part at meetings of the Society for Neurosciences, the College on Problems of Drug Dependence, the American Psychiatric Association, and the American College of Neuropsychopharmacology (1994Neuropsychopharmacology ( -1997 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript of cocaine itself, including generalized arousal, palpitations, light-head...

A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans (T2 weighted, 5 mm thick) of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T2 pixel values to correct field inhomogeneities ("shading"). Average (-SD) brain volume, excluding cerebellum, was 1090.91 ml (±# 114.30; range, 822.19-1363.66), and cerebrospinal fluid (CSF) volume was 127.91 ml (±57.62; range, 34.00-297.02). Brain volume was higher (by 5 ml) in the right hemisphere (P < 0.0001). Men (n = 34) had 91 ml higher brain and 20 ml higher CSF volume than women (n = 35). Age was negatively correlated with brain volume [r(67) =-0.32, P < 0.01] and positively correlated with CSF volume (r = 0.74, P < 0.0001). The slope of the regression line with age for CSF was steeper for men than women (P = 0.03). This difference in slopes was significant for sulcal (P < 0.0001), but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas in women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions.The study of brain regulation of human behavior requires measurement of structural variables, and this has been done primarily by postmortem studies (e.g., refs. 1-6). Atrophy was inferred from reduced brain weight or volume or increased differences between brain volume and cranial capacity-i.e., cerebrospinal fluid (CSF) volume. Several studies found aging associated with atrophy (7-9). Others did not find age effects until senescence (usually defined as age >55 or 60; refs. 4, 10, and 11). Women have lower brain volume, related to body and cranial size (e.g., refs. 4, 6, and 9).In vivo measurement of brain volume became feasible with computed tomography, and more recently with magnetic resonance imaging (MRI), which is more sensitive than computed tomography for determining sulcal changes and has better tissue contrast, multiplanar imaging capabilities, absence of bone artifact, and no ionizing radiation. In addition to elucidating structural substrates of brain function, anatomic volume measures are important for interpreting metabolic data (12). Thus, decline in cerebral blood flow and metabolism with age (e.g., refs. 13-15), and higher cerebral blood flow in women (16), could be explained by structural effects (17).Several computed tomography studies investigated ageassociated changes. Takeda and Matsuzawa (18) subjects aged 21-81 studied with a 2-T magnet and a spinlattice relaxation time (T1)-weighted sequence. However, in contrast to the other studies, which yielded brain volume estimates averaging 1100-1200 ml, their estimates were >2000 ml for men and >1800 ml for women. Jernigan et al. (23) found a linear re...

Increased subcortical volumes in treated schizophrenic patients seem to be medication-induced hypertrophy. This hypertrophy could reflect structural adaptation to receptor blockade and may moderate the effects of neuroleptic treatment.

The results provide further evidence for age effects and sex differences in the neuromodulatory influences of dopamine on behavior in humans.

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.