Person:

Elman, Igor

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response.

Rationale and Objectives: There is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress. Methods We induced stress by injecting yohimbine (0.2–0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings. Results: Voxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble. Conclusions: The present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.

Background: This study sought to determine how esthetic appearance of babies may affect their motivational processing by the adults. Methodology and Principal Findings: Healthy men and women were administered two laboratory-based tasks: a) key pressing to change the viewing time of normal-looking babies and of those with abnormal facial features (e.g., cleft palate, strabismus, skin disorders, Down's syndrome and fetal alcohol syndrome) and b) attractiveness ratings of these images. Exposure to the babies' images produced two different response patterns: for normal babies, there was a similar effort by the two groups to extend the visual processing with lower attractiveness ratings by men; for abnormal babies, women exerted greater effort to shorten the viewing time despite attractiveness ratings comparable to the men. Conclusions: These results indicate that gender differences in the motivational processing of babies include excessive (relative to the esthetic valuation) motivation to extend the viewing time of normal babies by men vs. shortening the exposure to the abnormal babies by women. Such gender-specific incentive sensitization phenomenon may reflect an evolutionary-derived need for diversion of limited resources to the nurturance of healthy offspring.

Rationale: Several lines of evidence suggest that cocaine expectancy and craving are two related phenomena. The present study assessed this potential link by contrasting reactions to varying degrees of the drug's perceived availability. Method: Non-treatment seeking individuals with cocaine dependence were administered an intravenous bolus of cocaine (0.2 mg/kg) under 100% ('unblinded'; N = 33) and 33% ('blinded'; N = 12) probability conditions for the delivery of drug. Subjective ratings of craving, high, rush and low along with heart rate and blood pressure measurements were collected at baseline and every minute for 20 minutes following the infusions. Results: Compared to the 'blinded' subjects, their 'unblinded' counterparts had similar craving scores on a multidimensional assessment several hours before the infusion, but reported higher craving levels on a more proximal evaluation, immediately prior to the receipt of cocaine. Furthermore, the 'unblinded' subjects displayed a more rapid onset of high and rush cocaine responses along with significantly higher cocaine-induced heart rate elevations. Conclusion: These results support the hypothesis that cocaine expectancy modulates subjective and objective responses to the drug. Provided the important public health policy implications of heavy cocaine use, health policy makers and clinicians alike may favor cocaine craving assessments performed in the settings with access to the drug rather than in more neutral environments as a more meaningful marker of disease staging and assignment to the proper level of care.

In rodents, corticosterone (cortisol in humans) facilitates cocaine self-administration purportedly via enhancement of dopaminergic activity in the brain. This study sought to assess central dopaminergic effects of cortisol in humans and to compare them to those of cocaine. Twelve cocaine-dependent individuals received an intravenous bolus of cortisol (0.5 and 0.2 mg/kg; n=6 for each dose) and cocaine (0.2 mg/kg) in a double-blind randomized placebo-controlled and counterbalanced fashion. Their plasma was assayed over the next 120 min for prolactin and growth hormone (GH), which are two neuroendocrine indices of dopaminergic function. Cortisol injections produced significant increases in GH, while cocaine resulted in significant decreases in prolactin. Placebo administration was associated with gradual declines in prolactin, but the levels at the 90- and 120-min time points were significantly lower after cocaine than after placebo infusion. These different neuroendocrine response profiles point to important differences between dopaminergic effects of cortisol and cocaine.

The aim of this study was to explore a potential link between psychosocial stress and cocaine dependence among 36 non-treatment-seeking individuals enrolled in a brain imaging protocol. Stress was assessed using computerized multidimensional instruments, including the Profile of Mood States (POMS) and Speilberger State-Trait Anxiety Inventory (STAI). Additional clinical assessments employed were the Addiction Severity Index and the Hamilton Rating Scale for Depression (HRSD). Based on the median POMS' tension-anxiety scale score the entire sample was divided into two groups, those with high and low levels of stress. The two groups (n = 16 and 20) were similar in terms of age, gender distribution, and severity of addiction. Compared with the low stress group, high-stress individuals displayed significantly longer duration of cocaine use, greater POMS, STAI-state, STAI-Trait, and HRSD scores. Our results replicate those of prior reports implicating stress in the course of cocaine dependence and extend these prior findings by 1) including a new subject population of non-treatment-seekers and 2) by suggesting that the stress-cocaine link may be generalizable to psychosocial stress and negative affective states defined by POMS, STAI, and HRSD scores.

Gender may be involved in the motivational processing of facial beauty. This study applied a behavioral probe, known to activate brain motivational regions, to healthy heterosexual subjects. Matched samples of men and women were administered two tasks: (a) key pressing to change the viewing time of average or beautiful female or male facial images, and (b) rating the attractiveness of these images. Men expended more effort (via the key-press task) to extend the viewing time of the beautiful female faces. Women displayed similarly increased effort for beautiful male and female images, but the magnitude of this effort was substantially lower than that of men for beautiful females. Heterosexual facial attractiveness ratings were comparable in both groups. These findings demonstrate heterosexual specificity of facial motivational targets for men, but not for women. Moreover, heightened drive for the pursuit of heterosexual beauty in the face of regular valuational assessments, displayed by men, suggests a gender-specific incentive sensitization phenomenon.

Background: Posttraumatic stress disorder (PTSD) may be associated with dysfunctional reward processing. The present study assessed for such dysfunction in both the expectancy and outcome phases of reward processing. Methods: Male Vietnam veterans with (n = 15) and without (n = 11) combat-related PTSD were administered a wheel of fortune-type gambling task. Self-reported ratings of expectancy and satisfaction were collected respectively before and after each experience of monetary gain or loss. Results: PTSD participants reported both lower expectancy of reward and lower satisfaction with reward when it was received. The latter result was manifest in a failure of PTSD participants to show the greater satisfaction that normally accompanies rewards received under conditions of low expectancy. Conclusion: These results suggest reward function impairment in PTSD related to expectancy, satisfaction, and the expectancy-satisfaction relationship.