Using the Veil of Ignorance to align AI systems with principles of justice.

The philosopher John Rawls proposed the Veil of Ignorance (VoI) as a thought experiment to identify fair principles for governing a society. Here, we apply the VoI to an important governance domain: artificial intelligence (AI). In five incentive-compatible studies (N = 2, 508), including two preregistered protocols, participants choose principles to govern an Artificial Intelligence (AI) assistant from behind the veil: that is, without knowledge of their own relative position in the group. Compared to participants who have this information, we find a consistent preference for a principle that instructs the AI assistant to prioritize the worst-off. Neither risk attitudes nor political preferences adequately explain these choices. Instead, they appear to be driven by elevated concerns about fairness: Without prompting, participants who reason behind the VoI more frequently explain their choice in terms of fairness, compared to those in the Control condition. Moreover, we find initial support for the ability of the VoI to elicit more robust preferences: In the studies presented here, the VoI increases the likelihood of participants continuing to endorse their initial choice in a subsequent round where they know how they will be affected by the AI intervention and have a self-interested motivation to change their mind. These results emerge in both a descriptive and an immersive game. Our findings suggest that the VoI may be a suitable mechanism for selecting distributive principles to govern AI.

Vector-based navigation using grid-like representations in artificial agents.

Deep neural networks have achieved impressive successes in fields ranging from object recognition to complex games such as Go1,2. Navigation, however, remains a substantial challenge for artificial agents, with deep neural networks trained by reinforcement learning3-5 failing to rival the proficiency of mammalian spatial behaviour, which is underpinned by grid cells in the entorhinal cortex 6 . Grid cells are thought to provide a multi-scale periodic representation that functions as a metric for coding space7,8 and is critical for integrating self-motion (path integration)6,7,9 and planning direct trajectories to goals (vector-based navigation)7,10,11. Here we set out to leverage the computational functions of grid cells to develop a deep reinforcement learning agent with mammal-like navigational abilities. We first trained a recurrent network to perform path integration, leading to the emergence of representations resembling grid cells, as well as other entorhinal cell types 12 . We then showed that this representation provided an effective basis for an agent to locate goals in challenging, unfamiliar, and changeable environments-optimizing the primary objective of navigation through deep reinforcement learning. The performance of agents endowed with grid-like representations surpassed that of an expert human and comparison agents, with the metric quantities necessary for vector-based navigation derived from grid-like units within the network. Furthermore, grid-like representations enabled agents to conduct shortcut behaviours reminiscent of those performed by mammals. Our findings show that emergent grid-like representations furnish agents with a Euclidean spatial metric and associated vector operations, providing a foundation for proficient navigation. As such, our results support neuroscientific theories that see grid cells as critical for vector-based navigation7,10,11, demonstrating that the latter can be combined with path-based strategies to support navigation in challenging environments.

Nonmonotonic recruitment of ventromedial prefrontal cortex during remote memory recall.

Systems-level consolidation refers to the time-dependent reorganisation of memory traces in the neocortex, a process in which the ventromedial prefrontal cortex (vmPFC) has been implicated. Capturing the precise temporal evolution of this crucial process in humans has long proved elusive. Here, we used multivariate methods and a longitudinal functional magnetic resonance imaging (fMRI) design to detect, with high granularity, the extent to which autobiographical memories of different ages were represented in vmPFC and how this changed over time. We observed an unexpected time course of vmPFC recruitment during retrieval, rising and falling around an initial peak of 8-12 months, before reengaging for older 2- and 5-year-old memories. This pattern was replicated in 2 independent sets of memories. Moreover, it was further replicated in a follow-up study 8 months later with the same participants and memories, for which the individual memory representations had undergone their hypothesised strengthening or weakening over time. We conclude that the temporal engagement of vmPFC in memory retrieval seems to be nonmonotonic, revealing a complex relationship between systems-level consolidation and prefrontal cortex recruitment that is unaccounted for by current theories.

Semantic representations in the temporal pole predict false memories.

Recent advances in neuroscience have given us unprecedented insight into the neural mechanisms of false memory, showing that artificial memories can be inserted into the memory cells of the hippocampus in a way that is indistinguishable from true memories. However, this alone is not enough to explain how false memories can arise naturally in the course of our daily lives. Cognitive psychology has demonstrated that many instances of false memory, both in the laboratory and the real world, can be attributed to semantic interference. Whereas previous studies have found that a diverse set of regions show some involvement in semantic false memory, none have revealed the nature of the semantic representations underpinning the phenomenon. Here we use fMRI with representational similarity analysis to search for a neural code consistent with semantic false memory. We find clear evidence that false memories emerge from a similarity-based neural code in the temporal pole, a region that has been called the "semantic hub" of the brain. We further show that each individual has a partially unique semantic code within the temporal pole, and this unique code can predict idiosyncratic patterns of memory errors. Finally, we show that the same neural code can also predict variation in true-memory performance, consistent with an adaptive perspective on false memory. Taken together, our findings reveal the underlying structure of neural representations of semantic knowledge, and how this semantic structure can both enhance and distort our memories.

Hippocampal damage and memory impairment in congenital cyanotic heart disease.

Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2017 Wiley Periodicals, Inc.

CA3 size predicts the precision of memory recall.

There is enduring interest in why some of us have clearer memories than others, given the substantial individual variation that exists in retrieval ability and the precision with which we can differentiate past experiences. Here we report novel evidence showing that variation in the size of human hippocampal subfield CA3 predicted the amount of neural interference between episodic memories within CA3, which in turn predicted how much retrieval confusion occurred between past memories. This effect was not apparent in other hippocampal subfields. This shows that subtle individual differences in subjective mnemonic experience can be accurately gauged from measurable variations in the anatomy and neural coding of hippocampal region CA3. Moreover, this mechanism may be relevant for understanding memory muddles in aging and pathological states.

Sparse encoding of automatic visual association in hippocampal networks.

Intelligent action entails exploiting predictions about associations between elements of ones environment. The hippocampus and mediotemporal cortex are endowed with the network topology, physiology, and neurochemistry to automatically and sparsely code sensori-cognitive associations that can be reconstructed from single or partial inputs. Whilst acquiring fMRI data and performing an attentional task, participants were incidentally presented with a sequence of cartoon images. By assigning subjects a post-scan free-association task on the same images we assayed the density of associations triggered by these stimuli. Using multivariate Bayesian decoding, we show that human hippocampal and temporal neocortical structures host sparse associative representations that are automatically triggered by visual input. Furthermore, as predicted theoretically, there was a significant increase in sparsity in the Cornu Ammonis subfields, relative to the entorhinal cortex. Remarkably, the sparsity of CA encoding correlated significantly with associative memory performance over subjects; elsewhere within the temporal lobe, entorhinal, parahippocampal, perirhinal and fusiform cortices showed the highest model evidence for the sparse encoding of associative density. In the absence of reportability or attentional confounds, this charts a distribution of visual associative representations within hippocampal populations and their temporal lobe afferent fields, and demonstrates the viability of retrospective associative sampling techniques for assessing the form of reflexive associative encoding.

Mapping taste and flavour traits to genetic markers in lettuce Lactuca sativa.

Lettuce is the most highly consumed raw leafy vegetable crop eaten worldwide, making it nutritionally important in spite of its comparatively low nutrient density in relation to other vegetables. However, the perception of bitterness caused by high levels of sesquiterpenoid lactones and comparatively low levels of sweet tasting sugars limits palatability. To assess variation in nutritional and taste-related metabolites we assessed 104 members of a Lactuca sativa cv. Salinas x L. serriola (accession UC96US23) mapping population. Plants were grown in three distinct environments, and untargeted NMR and HPLC were used as a rapid chemotyping method, from which 63 unique Quantitative Trait Loci (QTL) were identified. We were able to identify putative regulatory candidate genes underlying the QTL for fructose on linkage group 9, which accounted for up to 36 % of our population variation, and which was stable across all three growing environments; and for 15-p-hydroxyyphenylacetyllactucin-8-sulfate on linkage group 5 which has previously been identified for its low bitterness, while retaining anti-herbivory field effects. We also identified a candidate gene for flavonoid 3',5'- hydroxylase underlying a polyphenol QTL on linkage group 5, and two further candidate genes in sugar biosynthesis on linkage groups 2 and 5. Collectively these candidate genes and their associated markers can inform a route for plant breeders to improve the palatability and nutritional value of lettuce in their breeding programmes.

Detecting representations of recent and remote autobiographical memories in vmPFC and hippocampus.

How autobiographical memories are represented in the human brain and whether this changes with time are questions central to memory neuroscience. Two regions in particular have been consistently implicated, the ventromedial prefrontal cortex (vmPFC) and the hippocampus, although their precise contributions are still contested. The key question in this debate, when reduced to its simplest form, concerns where information about specific autobiographical memories is located. Here, we availed ourselves of the opportunity afforded by multivoxel pattern analysis to provide an alternative to conventional neuropsychological and fMRI approaches, by detecting representations of individual autobiographical memories in patterns of fMRI activity. We examined whether information about specific recent (two weeks old) and remote (10 years old) autobiographical memories was represented in vmPFC and hippocampus, and other medial temporal and neocortical regions. vmPFC contained information about recent and remote autobiographical memories, although remote memories were more readily detected there, indicating that consolidation or a change of some kind had occurred. Information about both types of memory was also present in the hippocampus, suggesting it plays a role in the retrieval of vivid autobiographical memories regardless of remoteness. Interestingly, we also found that while recent and remote memories were both represented within anterior and posterior hippocampus, the latter nevertheless contained more information about remote memories. Thus, like vmPFC, the hippocampus too respected the distinction between recent and remote memories. Overall, these findings clarify and extend our view of vmPFC and hippocampus while also informing systems-level consolidation and providing clear targets for future studies.

Representations of recent and remote autobiographical memories in hippocampal subfields.

The hippocampus has long been implicated in supporting autobiographical memories, but little is known about how they are instantiated in hippocampal subfields. Using high-resolution functional magnetic resonance imaging (fMRI) combined with multivoxel pattern analysis we found that it was possible to detect representations of specific autobiographical memories in individual hippocampal subfields. Moreover, while subfields in the anterior hippocampus contained information about both recent (2 weeks old) and remote (10 years old) autobiographical memories, posterior CA3 and DG only contained information about the remote memories. Thus, the hippocampal subfields are differentially involved in the representation of recent and remote autobiographical memories during vivid recall.

Normative development of white matter tracts: similarities and differences in relation to age, gender, and intelligence.

The white matter of the brain undergoes a range of structural changes throughout development; from conception to birth, in infancy, and onwards through childhood and adolescence. Several studies have used diffusion magnetic resonance imaging (dMRI) to investigate these changes, but a consensus has not yet emerged on which white matter tracts undergo changes in the later stages of development or what the most important driving factors are behind these changes. In this study of typically developing 8- to 16-year-old children, we use a comprehensive data-driven approach based on principal components analysis to identify effects of age, gender, and brain volume on dMRI parameters, as well as their relative importance. We also show that secondary components of these parameters predict full-scale IQ, independently of the age- and gender-related effects. This overarching assessment of the common factors and gender differences in normal white matter tract development will help to advance understanding of this process in late childhood and adolescence.

Sesquiterpenoids lactones: benefits to plants and people.

Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the role of sesquiterpene lactones endogenously in the plants that produce them, and explores mechanisms by which they interact in animal and human consumers of these plants. Several mechanisms are proposed for the reduction of inflammation and tumorigenesis at potentially achievable levels in humans. Plants can be classified by their specific array of produced sesquiterpene lactones, showing high levels of translational control. Studies of folk medicines implicate sesquiterpene lactones as the active ingredient in many treatments for other ailments such as diarrhea, burns, influenza, and neurodegradation. In addition to the anti-inflammatory response, sesquiterpene lactones have been found to sensitize tumor cells to conventional drug treatments. This review explores the varied ecological roles of sesquiterpenes in the plant producer, depending upon the plant and the compound. These include allelopathy with other plants, insects, and microbes, thereby causing behavioural or developmental modification to these secondary organisms to the benefit of the sesquiterpenoid producer. Some sesquiterpenoid lactones are antimicrobial, disrupting the cell wall of fungi and invasive bacteria, whereas others protect the plant from environmental stresses that would otherwise cause oxidative damage. Many of the compounds are effective due to their bitter flavor, which has obvious implications for human consumers. The implications of sesquiterpenoid lactone qualities for future crop production are discussed.

A systematic review of economic evaluations of pharmacist services.

BACKGROUND: Challenges to the provision of health care are occurring internationally and are expected to increase in the future, further increasing health spending. As pharmacist roles are evolving and expanding internationally to provide individualised pharmaceutical care it is important to assess the cost-effectiveness of these services. OBJECTIVES: To systematically synthesise the international literature regarding published economic evaluations of pharmacy services to assess their cost-effectiveness and clinical outcomes. METHODS: A systematic review of economic evaluations of pharmacy services was conducted in MEDLINE, EMBASE, PubMed, Scopus, Web of Science, CINAHL, IPA and online journals with search functions likely to publish economic evaluations of pharmacy services. Data were extracted regarding the interventions, the time horizon, the outcomes and the incremental cost-effectiveness ratio. Studies' quality of reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) statement. RESULTS: Seventy-five studies were included in the systematic review, including 67 cost-effectiveness analyses, 6 cost-benefit analyses and 2 cost-consequence analyses. Of these, 57 were either dominant or cost-effective using a willingness-to-pay threshold of NZ$46 645 per QALY. A further 11 studies' cost-effectiveness were unable to be evaluated. Interventions considered to be most cost-effective included pharmacist medication reviews, pharmacist adherence strategies and pharmacist management of type 2 diabetes mellitus, hypertension and warfarin/INR monitoring. The quality of reporting of studies differed with no studies reporting all 28 items of the CHEERS statement. CONCLUSIONS: There is strong economic evidence to support investment in extended pharmacist services, particularly those focussed on long-term chronic health conditions.

Genotypes of Eruca vesicaria subsp. sativa grown in contrasting field environments differ on transcriptomic and metabolomic levels, significantly impacting nutritional quality.

Rocket (Eruca vesicaria subsp. sativa) is a source of sulfur-containing glucosinolates (GSLs). GSLs and their breakdown hydrolysis products (GHPs) are responsible for health-related benefits, such as anti-cancer and anti-neurodegenerative properties. Understanding how phytochemical composition changes between cultivation environments is key to developing cultivars with improved nutritional quality. Two consecutive harvests (first and second regrowth) of crops, grown in both Italy and the UK, were used to determine the phytochemical and transcriptomic differences between six lines of Eruca. Samples were taken upon delivery from field sites (D0) and after five days of cold storage (D5) for each location. Leaves were analysed for sulfur content, volatile organic compounds (VOCs), GSLs, GHPs, and sugars. Transcriptome data were associated with metabolite profiles to identify differentially expressed genes between plants grown in the two environments. VOC compounds (carbon disulfide, methyl thiocyanate) were associated with growth environment and with differences in sulfur metabolism gene expression (APR2, LSU2, LSU3, SDI1, SiR), GSL biosynthesis (MYB28, FMOGS-OX2) and GHP formation (ESM1, TGG1, TGG2). The concentrations of sugars were an order of magnitude greater in UK grown samples (up to 29.9 mg g-1 dry weight; dw). Sulfur content was significantly higher in the Italy plant samples (11.4 - 20.1 mg g-1 dw), which was in turn associated with higher concentrations of GSLs (pentyl GSL, up to 15.8 µmol g-1 dw; sinigrin, up to 0.005 µmol g-1 dw; glucoraphanin, up to 5.1 µmol g-1 dw; glucorucolamine, up to 23.6 µmol g-1 dw; neoglucobrassicin, up to 5.3 µmol g-1 dw) and hydrolysis products (sativin, up to 13.5 µmol g-1 dw; erucin, up to 1 µmol g-1 dw; sulforaphane, up to 34.7 µmol g-1 dw). VOC profiles of plants cultivated in the UK were distinct from Italy grown plants, with higher relative abundances of alkanes and esters in second cut and shelf-life (D5) samples. The data indicate a significant interaction of cultivar response with environment, highlighting the difficulty of producing Eruca crops with consistent phytochemical and postharvest traits. Genes with differential expression between plants grown in Italy and the UK could be used as markers of phytochemical quality and composition.

Decoding representations of scenes in the medial temporal lobes.

Recent theoretical perspectives have suggested that the function of the human hippocampus, like its rodent counterpart, may be best characterized in terms of its information processing capacities. In this study, we use a combination of high-resolution functional magnetic resonance imaging, multivariate pattern analysis, and a simple decision making task, to test specific hypotheses concerning the role of the medial temporal lobe (MTL) in scene processing. We observed that while information that enabled two highly similar scenes to be distinguished was widely distributed throughout the MTL, more distinct scene representations were present in the hippocampus, consistent with its role in performing pattern separation. As well as viewing the two similar scenes, during scanning participants also viewed morphed scenes that spanned a continuum between the original two scenes. We found that patterns of hippocampal activity during morph trials, even when perceptual inputs were held entirely constant (i.e., in 50% morph trials), showed a robust relationship with participants' choices in the decision task. Our findings provide evidence for a specific computational role for the hippocampus in sustaining detailed representations of complex scenes, and shed new light on how the information processing capacities of the hippocampus may influence the decision making process.

Decoding overlapping memories in the medial temporal lobes using high-resolution fMRI.

The hippocampus is proposed to process overlapping episodes as discrete memory traces, although direct evidence for this in human episodic memory is scarce. Using green-screen technology we created four highly overlapping movies of everyday events. Participants were scanned using high-resolution fMRI while recalling the movies. Multivariate pattern analysis revealed that the hippocampus supported distinct representations of each memory, while neighboring regions did not, demonstrating that the human hippocampus maintains unique pattern-separated memory traces even when memories are highly overlapping. The hippocampus also contained representations of spatial contexts that were shared across different memories, consistent with a specialized role in processing space.

Quantitative trait loci analysis of glucosinolate, sugar, and organic acid concentrations in Eruca vesicaria subsp. sativa.

Eruca vesicaria subsp. sativa is a leafy vegetable of the Brassicaceae family known for its pungency. Variation in growing conditions, leaf age, agronomic practices, and variety choice lead to inconsistent quality, especially in content of isothiocyanates (ITCs) and their precursor glucosinolates (GSLs). We present the first linkage and Quantitative Trait Loci (QTL) map for Eruca, generated using a population of 139 F4 lines. A significant environmental effect on the abundance of primary and secondary metabolites was observed, with UK-grown plants containing significantly higher concentrations of glucoraphanin, malic acid, and total sugars. Italian-grown plants were characterized by higher concentrations of glucoerucin, indolic GSLs, and low monosaccharides. 20 QTL were identified and associated with robust SNP markers. Five genes putatively associated with the synthesis of the GSL 4-methoxyglucobrassicin (4MGB) were identified as candidate regulators underlying QTL. Analysis revealed that orthologs of MYB51, IGMT1 and IGMT4 present on LG1 are associated with 4MGB concentrations in Eruca. This research illustrates the utility of the map for identifying genes associated with nutritional composition in Eruca and its value as a genetic resource to assist breeding programs for this leafy vegetable crop.

Corrigendum: The Eruca sativa genome and transcriptome: A targeted analysis of sulfur metabolism and glucosinolate biosynthesis pre and postharvest.

[This corrects the article DOI: 10.3389/fpls.2020.525102.].

What can classic Atari video games tell us about the human brain?

In this issue of Neuron, Cross et. al (2021) use a deep reinforcement learning algorithm to understand human neural activation evoked by playing different video games. The results shed light on the neural principles underlying reward-guided decisions in naturalistic domains.

The History of Allied Health: An International Perspective.

The term allied health is not an uncommon one within the healthcare lexicon. However, the derivation and meaning of the term sit within the murkiness of history, making relevance in the current context perplexing. This article sets out to explore the origins of the term, and in turn how the term and its associated meaning have developed internationally. To give perspective, case studies of the term within the United States, Australia, Scotland, and New Zealand are used. Each is traced within discoverable literature, and a conclusion is drawn as to how the term within these case studies developed, the impact of the term, and whether the term is seen as symbolic or associative.