A Specialized Odor Memory Buffer in Primary Olfactory Cortex

The neural substrates of olfactory working memory are unknown. We addressed the questions of whether olfactory working memory involves a verbal representation of the odor, or a sensory image of the odor, or both, and the location of the neural substrates of these processes.We used functional magnetic resonance imaging to measure activity in the brains of subjects who were remembering either nameable or unnameable odorants. We found a double dissociation whereby remembering nameable odorants was reflected in sustained activity in prefrontal language areas, and remembering unnameable odorants was reflected in sustained activity in primary olfactory cortex.These findings suggest a novel dedicated mechanism in primary olfactory cortex, where odor information is maintained in temporary storage to subserve ongoing tasks

Decreased olfactory discrimination is associated with impulsivity in healthy volunteers

In clinical populations, olfactory abilities parallel executive function, implicating shared neuroanatomical substrates within the ventral prefrontal cortex. In healthy individuals, the relationship between olfaction and personality traits or certain cognitive and behavioural characteristics remains unexplored. We therefore tested if olfactory function is associated with trait and behavioural impulsivity in nonclinical individuals. Eighty-three healthy volunteers (50 females) underwent quantitative assessment of olfactory function (odour detection threshold, discrimination, and identifcation). Each participant was rated for trait impulsivity index using the Barratt Impulsiveness Scale and performed a battery of tasks to assess behavioural impulsivity (Stop Signal Task, SST; Information Sampling Task, IST; Delay Discounting). Lower odour discrimination predicted high ratings in non-planning impulsivity (Barratt Non-Planning impulsivity subscale); both, lower odour discrimination and detection threshold predicted low inhibitory control (SST; increased motor impulsivity). These fndings extend clinical observations to support the hypothesis that defcits in olfactory ability are linked to impulsive tendencies within the healthy population. In particular, the relationship between olfactory abilities and behavioural inhibitory control (in the SST) reinforces evidence for functional overlap between neural networks involved in both processes. These fndings may usefully inform the stratifcation of people at risk of impulse-control-related problems and support planning early clinical interventions

Gender distribution of adult patients on highly active antiretroviral therapy (HAART) in Southern Africa: a systematic review

Background: HIV and AIDS are significant and growing public health concerns in southern Africa. The majority of countries in the region have national adult HIV prevalence estimates exceeding 10 percent. The increasing availability of highly active antiretroviral therapy (HAART) has potential to mitigate the situation. There is however concern that women may experience more barriers in accessing treatment programs than men. Methods: A systematic review of the literature was carried out to describe the gender distribution of patients accessing highly active antiretroviral therapy (HAART) in Southern Africa. Data on number of patients on treatment, their mean or median age and gender were obtained and compared across studies and reports. Results: The median or mean age of patients in the studies ranged from 33 to 39 years. While female to male HIV infection prevalence ratios in the southern African countries ranged from 1.2:1 to 1.6:1, female to male ratios on HAART ranged from 0.8: 1 to 2.3: 1. The majority of the reports had female: male ratio in treatment exceeding 1.6. Overall, there were more females on HAART than there were males and this was not solely explained by the higher HIV prevalence among females compared to males. Conclusion: In most Southern African countries, proportionally more females are on HIV antiretroviral treatment than men, even when the higher HIV infection prevalence in females is accounted for. There is need to identify the factors that are facilitating women's accessibility to HIV treatment. As more patients access HAART in the region, it will be important to continue assessing the gender distribution of patients on HAART.Peer Reviewe

Methylphenidate Normalizes Fronto-Striatal Underactivation During Interference Inhibition in Medication-Naïve Boys with Attention-Deficit Hyperactivity Disorder

Youth with attention deficit hyperactivity disorder (ADHD) have deficits in interference inhibition, which can be improved with the indirect catecholamine agonist methylphenidate (MPH). Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys. Medication-naïve boys with ADHD were scanned twice, in a randomized, double-blind design, under either a single clinical dose of MPH or placebo, while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys. During incongruent trials compared with congruent–oddball trials, boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition, including right inferior prefrontal cortex, left striatum and thalamus, mid-cingulate/supplementary motor area, and left superior temporal lobe. MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices. Under the MPH condition, patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions. Effect size comparison, furthermore, showed that these normalization effects were significant. MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition, but did not affect medial frontal or temporal dysfunction. MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Brief Optogenetic Inhibition of Dopamine Neurons Mimics Endogenous Negative Reward Prediction Errors

Correlative studies have strongly linked phasic changes in dopamine activity with reward prediction error signaling. But causal evidence that these brief changes in firing actually serve as error signals to drive associative learning is more tenuous. While there is direct evidence that brief increases can substitute for positive prediction errors, there is no comparable evidence that similarly brief pauses can substitute for negative prediction errors. Lacking such evidence, the effect of increases in firing could reflect novelty or salience, variables also correlated with dopamine activity. Here we provide such evidence, showing in a modified Pavlovian over-expectation task that brief pauses in the firing of dopamine neurons in rat ventral tegmental area at the time of reward are sufficient to mimic the effects of endogenous negative prediction errors. These results support the proposal that brief changes in the firing of dopamine neurons serve as full-fledged bidirectional prediction error signals