Effects of oral 5-hydroxytryptophan on a standardized planning task: insight into possible dopamine/serotonin interactions in the forebrain.

OBJECTIVE: Several studies have suggested that exogenous administration of the serotonin precursor 5-hydroxytryptophan (5-HTP) can result in the ectopic production of serotonin in dopaminergic neurons and a concomitant reduction in dopamine release. This study tested this hypothesis using the Tower of London (TOL), a test of planning and executive control that is sensitive to changes in forebrain dopamine activity, but insensitive to alterations in serotonin. METHODS: A sample of 68 undergraduates participated, and each received either three 50-mg 5-HTP capsules or placebos, and completed the TOL following a set absorption period. RESULTS: 5-HTP significantly lengthened the average time needed to complete each of the 10 trials of the TOL. 5-HTP did not affect accuracy on this task. CONCLUSIONS: Oral exogenous 5-HTP disrupts dopaminergic function in the human forebrain.

Can the 8-coil Shakti alter subjective emotional experience? A randomized, placebo-controlled study.

At present, a commercially available device (the 8-coil Shakti) claims to produce weak and complex magnetic fields that alter neurobiological processes. The effects of the Shakti on emotional responses to photographs that varied on emotional valence were investigated. Participants (N = 37) were exposed to either 30 min, of magnetic fields or a sham condition and rated their emotional reactions to a set of 54 color photographs. Although participants indicated significantly different emotional responses to images with distinct emotional valences, exposure to magnetic fields did not affect these responses, nor significantly interact with image emotional valence. Although the device's "amygdala signal" had no effect on the emotive response to images in this study, additional investigations examining the effects of weak and complex magnetic fields on various aspects of perception and cognition are warranted.

Oral administration of 5-hydroxytryptophan (5-HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task.

OBJECTIVE: Although the serotonin precursor 5-hydroxytryptophan (5-HTP) is marketed as a psychoactive nutritional supplement, knowledge is limited regarding the effects of exogenous 5-HTP on brain activity. This study examined if oral administration of 5-HTP to healthy adults impacted: (1) mood states, as measured by the Profile of Mood States (POMS); and (2) performance on the Iowa Gambling Task (IGT), a measure sensitive to alterations in frontocortical serotonin levels. METHODS: A sample of 46 undergraduates participated, and each received either two 50 mg 5-HTP capsules or placebos, and completed the IGT and POMS following an absorption period. RESULTS: 5-HTP did not significantly alter mood states, but did impair performance on the IGT. Specifically, the 5-HTP group performed more poorly than the placebo group during the first 20 trials of the IGT but did not differ from the placebo group on trials 21-100. This suggests that oral 5-HTP specifically impaired decision making under ambiguity but not under risk. Males also performed more poorly on the first 20 trials of the IGT, regardless of treatment group. CONCLUSIONS: Oral 5-HTP is psychoactive at low doses. Decisions made under ambiguity may be differentially sensitive to increased serotonin release or associated reductions in frontocortical dopamine activity.

Functional relationships between serum total cholesterol levels, executive control, and sustained attention.

This study investigated the potential relationship between serum total cholesterol (TC) and two specific aspects of cognition (executive control and sustained attention) in a non-elderly sample, after controlling for life stress and several sociodemographic and health variables. For each participant (n = 46), measurements of TC, physical health, and life stress were obtained, and executive control and sustained attention were assessed using the Tower of London and the Digit Vigilance Test. The outcomes of these cognitive assessments were correlated with TC, and a covariate-adjusted analysis was performed. After controlling for several co-variates, TC was found to be significantly negatively associated with components of executive control and sustained attention. Because these cognitive functions are crucial in the moment-to-moment regulation of behavior, elevated TC may have negative behavioral consequences in everyday life situations.

The potential behavioral and economic impacts of widespread HMG-CoA reductase inhibitor (statin) use.

Dyslipidemia is a common pathology throughout the industrialized world, and HMG-CoA reductase inhibitors (statins) are often administered to treat elevated lipid levels. Substantial concern has been raised regarding the aggressive clinical lowering of cholesterol, particularly in light of a growing body of research linking low circulating lipid levels with negative behavioral outcomes in both human samples and non-human primate models. In 2009, Goldstein and colleagues tentatively speculated that the greed, impulsiveness, and lack of foresight that lead to the worldwide economic collapse in 2007-2008 could have been caused (in part) by depressed population cholesterol levels resulting from the widespread use of statins by workers in the financial services industry. This paper reviews the literature that links low circulating lipid levels with neurobehavioral dysfunction, develops Goldstein and colleagues' initial speculation into a formal hypothesis, and proposes several specific studies that could rigorously empirically evaluate this hypothesis.

The Problem of Dualism in Modern Western Medicine.

Dualism is historically important in that it allowed the medical practice to be divorced from church oversight. The reductionist approaches of modern Western medicine facilitate a dispassionate and mechanistic approach to patient care, and dualist views promoted by complementary and alternative medicine are also problematic. Behavioural disorders are multifactorally realizable and emerge apparently chaotically from interactions between internal physiological systems and the patient's environment and experiential history. Conceptualizations of behavioural disorders that are based on dualism deny the primacy of individual physiology in the generation of pathology and distract from therapies that are most likely to produce positive outcomes. Behavioural health professionals should adopt holistic models of patient care, but these models must be based on methodologies that emphasize radical emergence over the artificial separation of the "physical" and "mental." This will allow for the humanistic practice of medicine while simultaneously maximizing the likelihood of treatment success.

Enduring effects of prenatal cocaine exposure on selective attention and reactivity to errors: evidence from an animal model.

Adult Long-Evans rats, exposed prenatally to 1 of 4 doses of cocaine (0.0,0.5,1.0, or 3.0 mg/kg iv), were tested on a 3-choice visual attention task with an olfactory distractor presented unpredictably on one third of the trials. The performance of all 3 cocaine-exposed groups was significantly more disrupted than that of controls by the presentation of distractors. Results demonstrate that prenatal cocaine exposure increases susceptibility to distractors, using a task specifically designed to measure this function. In addition, the present study revealed that individuals exposed to cocaine in utero exhibit greater performance disruption after an error than controls, in certain types of tasks. Both areas of dysfunction, impaired selective attention and impaired arousal regulation, have important functional consequences in humans, possibly affecting the school performance and social development of cocaine-exposed children.

Impaired sustained attention and altered reactivity to errors in an animal model of prenatal cocaine exposure.

Although correlations have been reported between maternal cocaine use and impaired attention in exposed children, interpretation of these findings is complicated by the many risk factors that differentiate cocaine-exposed children from SES-matched controls. For this reason, the present dose-response study (0, 0.5, 1.0, or 3.0 mg/kg cocaine HCl) was designed to explore the effect of prenatal cocaine exposure on visual attention in a rodent model, using an intravenous injection protocol that closely mimics the pharmacokinetic profile and physiological effects of human recreational cocaine use. In adulthood, animals were tested on an attention task in which the duration, location, and onset time of a brief visual cue varied randomly between trials. The 3.0 mg/kg exposed males committed significantly more omission errors than control males during the final 1/3 of each testing session, specifically on trials that followed an error, which implicates impaired sustained attention and increased reactivity to committing an error. During the final 1/3 of each testing session, the 0.5 and 1.0 mg/kg exposed females took longer to enter the testing alcove at trial onset, and failed to enter the alcove more frequently than control females. Because these effects were not seen in other tasks of similar duration and reinforcement density, these findings suggest an impairment of sustained attention. This inference is supported by the finding that the increase in omission errors in the final block of trials in each daily session (relative to earlier in the session) was significantly greater for the 1.0 mg/kg females than for controls, a trend also seen for the 0.5 mg/kg group. Unlike the cocaine-exposed males, who remain engaged in the task when attention is waning, the cocaine-exposed females appear to opt for another strategy; namely, refusing to participate when their ability to sustain attention is surpassed.

Impaired neuropsychological functioning in lead-exposed children.

Neuropsychological functions were assessed in 174 children participating in a longitudinal study of low-level lead exposure. At age 5 1/2 years, children were administered the Working Memory and Planning Battery of the Cambridge Neuropsychological Testing Automated Battery. Measures of sociodemographic characteristics of the family, prenatal and perinatal risk, quality of caregiving and crowding in the home, and maternal and child intelligence were used as covariates to test the hypothesis that children with higher lifetime average blood lead concentrations would perform more poorly on tests of working memory, attentional flexibility, and planning and problem solving. The lifetime average blood lead level in this sample was 7.2 micrograms per deciliter (mug/dL; range: 0-20 mug/dL). Children with greater exposure performed more poorly on tests of executive processes. In both bivariate and multivariate analyses, children with higher lifetime average blood lead concentrations showed impaired performance on the tests of spatial working memory, spatial memory span, intradimensional and extradimensional shifts, and an analog of the Tower of London task. Many of the significant associations remained after controlling for children's intelligence test scores, in addition to the other covariates. These findings indicate that the effects of pediatric lead exposure are not restricted to global indexes of general intellectual functioning, and executive processes may be at particular risk of lead-induced neurotoxicity.

Prenatal cocaine exposure does not alter working memory in adult rats.

The present study was designed to assess working memory in adult rats exposed to intravenous cocaine in utero, as part of an examination of various cognitive and affective functions. The study included four groups: a saline control and three groups exposed to ascending doses of cocaine from gestational days 8 to 21 (0.5, 1.0, or 3.0 mg/kg). This exposure regimen (route of administration and dose) has been shown to accurately reproduce the pharmacokinetic profile and physiological effects of human recreational cocaine use. This report describes the results of a series of automated alternation tasks, in which the animals were rewarded for alternating their responses between two response ports on successive trials. In the final task, the delay between trials varied randomly between 0, 20, 40, and 80 s, thereby varying the retention interval. Although performance declined dramatically as the retention interval increased, the rate of this decline did not differ across treatment groups. These results suggest that prenatal cocaine exposure, at doses that model recreational use, does not produce lasting changes in explicit memory or working memory. However, subtle, sex-specific effects of prenatal cocaine exposure were seen on measures that indicate impairments in sustained attention and "readiness", as well as altered reactivity to task-related stressors such as waiting for long and unpredictable delays.

Word-gustatory synesthesia: a case study.

A case study of a rare form of synesthesia is presented, where specific words act as the inducer, and gustatory sensations function as the concurrent. The female participant (TD) was twice presented with a list of 806 English words and 222 grammatically correct non-words (with 3 months between presentations). For each presentation, TD was asked to provide: a subjective description of the gustatory experience (if any) associated with each stimulus; a rating (from 0 to 10) of the intensity of the gustatory experience; and an indication (yes/no) if the experience was aversive. TD's responses across the two presentations were quantified, and comparisons are provided. In addition, TD's ability to create and recall novel word-taste associations was compared to that demonstrated by a sample of ten age-matched non-synesthete females. TD's synesthetic experiences were found to be highly consistent, more common in English words than non-words, and rarely aversive. Although TD was superior to control participants in remembering novel word-taste associations, her reported experiences cannot be wholly explained by either an exceptional non-synesthetic learning of taste-word associations over time, or a clear response to phonemes, rather than whole words. These conclusions are compared to the five other published reports of word-gustatory synesthesia, and directions for future research are discussed.