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  • The attitudes of medical students to research.

    5 November 2018

    BACKGROUND: The workforce of 'physician--scientists' is ageing and decreasing in numbers. The responsibility to combat this trend rests on future generations of healthcare professionals and it is therefore valuable to evaluate medical students' attitudes towards research. OBJECTIVE: To establish the attitudes of University of Cape Town (UCT) medical students towards research and to investigate the factors influencing these attitudes. METHODS: An anonymous, cross--sectional, self--administered questionnaire was administered to medical students from years 1 to 6 studying medicine at UCT in 2011. Questions were primarily closed--ended and consisted of Likert scales. RESULTS: Out of a population of 1 195 medical students, 733 were sampled (63%); 65% were female, 53% were preclinical students (years 1 -- 3) and 47% were in their clinical years (year 4 -- 6). Overall, 61% of students had a positive attitude towards research and 74% felt that participation in research was important to their medical school education; 22% had been involved in voluntarily extracurricular research, 4% had presented at a scientific meeting and 3% had published in peer--reviewed journals. A number of perceived barriers to student research were identified including a lack of adequate training, time and research opportunities. CONCLUSION: Students believed that research was important and had a positive attitude towards it. However, few had been involved in voluntary research and produced work worthy of presentation and/or publication. Addressing identified barriers and improving students' attitudes may begin to reverse the trend in declining numbers of physician--scientists.

  • Genome-wide association studies of brain imaging phenotypes in UK Biobank.

    5 November 2018

    The genetic architecture of brain structure and function is largely unknown. To investigate this, we carried out genome-wide association studies of 3,144 functional and structural brain imaging phenotypes from UK Biobank (discovery dataset 8,428 subjects). Here we show that many of these phenotypes are heritable. We identify 148 clusters of associations between single nucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05, when we would expect 21 to replicate by chance. Notable significant, interpretable associations include: iron transport and storage genes, related to magnetic susceptibility of subcortical brain tissue; extracellular matrix and epidermal growth factor genes, associated with white matter micro-structure and lesions; genes that regulate mid-line axon development, associated with organization of the pontine crossing tract; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide insights into the genetic architecture of the brain that are relevant to neurological and psychiatric disorders, brain development and ageing.

  • Reconciling persistent and dynamic hypotheses of working memory coding in prefrontal cortex.

    15 November 2018

    Competing accounts propose that working memory (WM) is subserved either by persistent activity in single neurons or by dynamic (time-varying) activity across a neural population. Here, we compare these hypotheses across four regions of prefrontal cortex (PFC) in an oculomotor-delayed-response task, where an intervening cue indicated the reward available for a correct saccade. WM representations were strongest in ventrolateral PFC neurons with higher intrinsic temporal stability (time-constant). At the population-level, although a stable mnemonic state was reached during the delay, this tuning geometry was reversed relative to cue-period selectivity, and was disrupted by the reward cue. Single-neuron analysis revealed many neurons switched to coding reward, rather than maintaining task-relevant spatial selectivity until saccade. These results imply WM is fulfilled by dynamic, population-level activity within high time-constant neurons. Rather than persistent activity supporting stable mnemonic representations that bridge subsequent salient stimuli, PFC neurons may stabilise a dynamic population-level process supporting WM.

  • Triple dissociation of attention and decision computations across prefrontal cortex

    15 November 2018

    Anatomical, neuroimaging and lesion studies indicate that prefrontal cortex (PFC) can be subdivided into different subregions supporting distinct aspects of decision making. However, explanations of neuronal computations within these subregions varies widely across studies. An integrated and mechanistic account of PFC function therefore remains elusive. Resolving these debates demands a rich dataset that directly contrasts neuronal activity across multiple PFC subregions within a single paradigm, whilst experimentally controlling factors such as the order, duration and frequency in which choice options are attended and compared. Here, we contrast neuronal population responses between macaque orbitofrontal (OFC), anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC) during sequential value-guided information search and choice. From the first fixation of choice-related stimuli, a strong triple dissociation of information encoding emerges in parallel across these PFC subregions. As further information is gathered, population responses in OFC reflect an attention-guided value comparison process. Meanwhile, parallel signals in ACC reflect belief updating in light of new evidence, integration of that evidence to a decision bound, and an emerging action plan for which option should be chosen. Our findings demonstrate the co-existence of multiple, distributed decision-related computations across PFC subregions during value-guided choice. They provide a synthesis of several competing accounts of PFC function.

  • Approach-induced biases in human information sampling

    15 November 2018

    Information sampling is often biased towards seeking evidence that confirms one's prior beliefs. Despite such biases being a pervasive feature of human behavior, their underlying causes remain unclear. Many accounts of these biases appeal to limitations of human hypothesis testing and cognition, de facto evoking notions of bounded rationality, but neglect more basic aspects of behavioral control. Here we demonstrate involvement of Pavlovian approach biases in determining which information humans will choose to sample. We collected a large novel dataset from 32,445 human subjects, making over 3 million decisions, who played a gambling task designed to measure the latent causes and extent of information-sampling biases. We identified three novel approach-related biases, formalized by comparing subject behavior to a dynamic programming model of optimal information gathering. These biases reflected the amount of information sampled ('positive evidence approach'), the selection of which information to sample ('sampling the favorite'), and the interaction between information sampling and subsequent choices ('rejecting unsampled options'). The prevalence of all three biases was related to a Pavlovian approach-avoid parameter quantified within an entirely independent economic decision task. Our large dataset also revealed that individual differences in information seeking are a stable trait across multiple gameplays, and can be related to demographic measures including age and educational attainment. As well as revealing limitations in cognitive processing, our findings suggest information sampling biases reflect the expression of primitive, yet potentially ecologically adaptive, behavioral repertoires. One such behavior is sampling from options that will eventually be chosen, even when other sources of information are more pertinent for guiding future action.

  • Differential valuation and learning from social and non-social cues in Borderline Personality Disorder

    15 November 2018

    Background: Volatile interpersonal relationships are a core feature of Borderline Personality Disorder (BPD), and lead to devastating disruption of patients' personal and professional lives. Quantitative models of social decision making and learning hold promise for defining the underlying mechanisms of this problem. In this study, we tested BPD and control subject weighting of social versus non-social information, and their learning about choices under stable and volatile conditions. We compared behavior using quantitative models. Methods: Subjects (n=20 BPD, n=23 control) played an extended reward learning task with a partner (confederate) that requires learning about non-social and social cue reward probability (The Social Valuation Task). Task experience was measured using language metrics: explicit emotions/beliefs, talk about the confederate, and implicit distress (using the previously established marker self-referentiality). Subjects' weighting of social and non-social cues was tested in mixed-effects regression models. Subjects' learning rates under stable and volatile conditions were modelled (Rescorla-Wagner approach) and group x condition interactions tested. Results: Compared to controls, BPD subject debriefings included more mentions of the confederate and less distress language. BPD subjects also weighted social cues more heavily, but had blunted learning responses to (non-social and social) volatility. Conclusions: This is the first report of patient behavior in the Social Valuation Task. The results suggest that BPD subjects expect higher volatility than do controls. These findings lay the groundwork for a neuro-computational dissection of social and non-social belief updating in BPD, which holds promise for the development of novel clinical interventions that more directly target pathophysiology.