Neurophysiology of Human Perceptual Decision-Making.

The discovery of neural signals that reflect the dynamics of perceptual decision formation has had a considerable impact. Not only do such signals enable detailed investigations of the neural implementation of the decision-making process but they also can expose key elements of the brain's decision algorithms. For a long time, such signals were only accessible through direct animal brain recordings, and progress in human neuroscience was hampered by the limitations of noninvasive recording techniques. However, recent methodological advances are increasingly enabling the study of human brain signals that finely trace the dynamics of the unfolding decision process. In this review, we highlight how human neurophysiological data are now being leveraged to furnish new insights into the multiple processing levels involved in forming decisions, to inform the construction and evaluation of mathematical models that can explain intra- and interindividual differences, and to examine how key ancillary processes interact with core decision circuits.

A glycan receptor kinase facilitates intracellular accommodation of arbuscular mycorrhiza and symbiotic rhizobia in the legume Lotus japonicus.

Receptors that distinguish the multitude of microbes surrounding plants in the environment enable dynamic responses to the biotic and abiotic conditions encountered. In this study, we identify and characterise a glycan receptor kinase, EPR3a, closely related to the exopolysaccharide receptor EPR3. Epr3a is up-regulated in roots colonised by arbuscular mycorrhizal (AM) fungi and is able to bind glucans with a branching pattern characteristic of surface-exposed fungal glucans. Expression studies with cellular resolution show localised activation of the Epr3a promoter in cortical root cells containing arbuscules. Fungal infection and intracellular arbuscule formation are reduced in epr3a mutants. In vitro, the EPR3a ectodomain binds cell wall glucans in affinity gel electrophoresis assays. In microscale thermophoresis (MST) assays, rhizobial exopolysaccharide binding is detected with affinities comparable to those observed for EPR3, and both EPR3a and EPR3 bind a well-defined ß-1,3/ß-1,6 decasaccharide derived from exopolysaccharides of endophytic and pathogenic fungi. Both EPR3a and EPR3 function in the intracellular accommodation of microbes. However, contrasting expression patterns and divergent ligand affinities result in distinct functions in AM colonisation and rhizobial infection in Lotus japonicus. The presence of Epr3a and Epr3 genes in both eudicot and monocot plant genomes suggest a conserved function of these receptor kinases in glycan perception.

Rhizobial secretion of truncated exopolysaccharides severely impairs the Mesorhizobium-Lotus symbiosis.

The symbiosis between Mesorhizobium japonicum R7A and Lotus japonicus Gifu is an important model system for investigating the role of bacterial exopolysaccharides (EPS) in plant-microbe interactions. Previously we showed that R7A exoB mutants that are affected at an early stage of EPS synthesis and in lipopolysaccharide (LPS) synthesis induce effective nodules on L. japonicus Gifu after a delay, whereas exoU mutants affected in the biosynthesis of the EPS side chain induce small uninfected nodule primordia and are impaired in infection. The presence of a halo around the exoU mutant when grown on Calcofluor-containing media suggested the mutant secreted a truncated version of R7A EPS. A non-polar ΔexoA mutant defective in the addition of the first glucose residue to the EPS backbone was also severely impaired symbiotically. Here we used a suppressor screen to show that the severe symbiotic phenotype of the exoU mutant was due to secretion of an acetylated pentasaccharide, as both monomers and oligomers, by the same Wzx/Wzy system that transports wild-type exopolysaccharide. We also present evidence that the ΔexoA mutant secretes an oligosaccharide by the same transport system, contributing to its symbiotic phenotype. In contrast, ΔexoYF, and polar exoA and exoL mutants have a similar phenotype to exoB mutants, forming effective nodules after a delay. These studies provide substantial evidence that secreted incompatible EPS is perceived by the plant leading to abrogation of the infection process.

Economic evaluation of population-based, expanded reproductive carrier screening for genetic diseases in Australia.

PURPOSE: This study aimed to evaluate the cost effectiveness of population-based, expanded reproductive carrier screening (RCS) for a 300 recessive gene panel from health service and societal perspectives. METHODS: A microsimulation model (PreConMod) was developed using 2016 Australian Census data as the base population. Epidemiologic, health, and indirect cost data were based on literature review. The study assessed the incremental cost effectiveness ratio of expanded RCS compared with (1) no population screening and (2) 3-condition screening for cystic fibrosis, spinal muscular atrophy, and fragile X syndrome in a single birth cohort. Averted affected births and health service savings with expanded RCS were projected to year 2061. Both one-way and probability sensitivity analyses were conducted to assess the uncertainty of the parameter inputs. RESULTS: Expanded RCS was cost saving compared with no population screening and cost effective compared with the 3-condition screening (incremental cost effectiveness ratio of Australian dollar [AUD] 6287 per quality-adjusted life year gained) at an uptake rate of 50% for RCS, 59% for in vitro fertilization and preimplantation genetic testing, 90% for prenatal diagnosis testing, and 50% for elective termination of affected pregnancies and a cost of AUD595 per couple screened. Our model predicts that expanded RCS would avert one-third of affected births in a single birth cohort and reduce lifetime health service spending by AUD632.0 million. Expanded RCS was estimated to be cost saving from the societal perspective. CONCLUSION: Expanded RCS is cost effective from health service and societal perspectives. Expanded RCS is projected to avert significantly more affected births and result in health service saving beyond those expected from 3-condition screening or no population screening.

Characterization of Beef Coming from Different European Countries through Stable Isotope (H, C, N, and S) Ratio Analysis.

The need to guarantee the geographical origin of food samples has become imperative in recent years due to the increasing amount of food fraud. Stable isotope ratio analysis permits the characterization and origin control of foodstuffs, thanks to its capability to discriminate between products having different geographical origins and derived from different production systems. The Framework 6 EU-project "TRACE" generated hydrogen (2H/1H), carbon (13C/12C), nitrogen (15N/14N), and sulphur (34S/32S) isotope ratio data from 227 authentic beef samples. These samples were collected from a total of 13 sites in eight countries. The stable isotope analysis was completed by combining IRMS with a thermal conversion elemental analyzer (TC/EA) for the analysis of δ(2H) and an elemental analyzer (EA) for the determination of δ(13C), δ(15N), and δ(34S). The results show the potential of this technique to detect clustering of samples due to specific environmental conditions in the areas where the beef cattle were reared. Stable isotope measurements highlighted statistical differences between coastal and inland regions, production sites at different latitudes, regions with different geology, and different farming systems related to the diet the animals were consuming (primarily C3- or C4-based or a mixed one).

Distinct signaling routes mediate intercellular and intracellular rhizobial infection in Lotus japonicus.

Rhizobial infection of legume roots during the development of nitrogen-fixing root nodules can occur intracellularly, through plant-derived infection threads traversing cells, or intercellularly, via bacterial entry between epidermal plant cells. Although it is estimated that around 25% of all legume genera are intercellularly infected, the pathways and mechanisms supporting this process have remained virtually unexplored due to a lack of genetically amenable legumes that exhibit this form of infection. In this study, we report that the model legume Lotus japonicus is infected intercellularly by the IRBG74 strain, recently proposed to belong to the Agrobacterium clade of the Rhizobiaceae. We demonstrate that the resources available for L. japonicus enable insight into the genetic requirements and fine-tuning of the pathway governing intercellular infection in this species. Inoculation of L. japonicus mutants shows that Ethylene-responsive factor required for nodulation 1 (Ern1) and Leu-rich Repeat Receptor-Like Kinase (RinRK1) are dispensable for intercellular infection in contrast to intracellular infection. Other symbiotic genes, including nod factor receptor 5 (NFR5), symbiosis receptor-like kinase (SymRK), Ca2+/calmodulin dependent kinase (CCaMK), exopolysaccharide receptor 3 (Epr3), Cyclops, nodule inception (Nin), nodulation signaling pathway 1 (Nsp1), nodulation signaling pathway 2 (Nsp2), cystathionine-ß-synthase (Cbs), and Vapyrin are equally important for both entry modes. Comparative RNAseq analysis of roots inoculated with IRBG74 revealed a distinctive transcriptome response compared with intracellular colonization. In particular, several cytokinin-related genes were differentially regulated. Corroborating this observation, cyp735A and ipt4 cytokinin biosynthesis mutants were significantly affected in their nodulation with IRBG74, whereas lhk1 cytokinin receptor mutants formed no nodules. These results indicate a differential requirement for cytokinin signaling during intercellular rhizobial entry and highlight distinct modalities of inter- and intracellular infection mechanisms in L. japonicus.

Assessment of rapid low-cost isotope (δ15 N, δ18 O) analyses of nitrate in fruit extracts by Ti(III) reduction to differentiate organic from conventional production.

RATIONALE: The isotopic composition (δ15 N, δ18 O) of nitrate in fruits and vegetables differentiates organic from conventional food production practices. Organic systems do not use synthetic nitrate fertilizers high in 18 O and low in 15 N and thereby help reveal producers' fertilization claims. Isotope analyses of nitrate extracted from fruits and vegetables are done by bacterial reduction which is costly and by specialized laboratories. Rapid, low-cost methods are needed to promulgate nitrate isotope analyses of food products to support organic food product certification and to verify the authenticity of production claims. METHODS: Fresh strawberry samples were obtained from certified organic and conventional growers in Andalucía, Spain. We applied a new, rapid, one-step Ti(III) reduction method to convert the nitrate from strawberry extracts to N2 O gas for headspace isotope analyses using isotope-ratio mass spectrometry. Using the Ti(III) reduction method, 70 samples, controls and references were prepared and analyzed for NO3 - , δ15 N and δ18 O per 48 h. We also analyzed extracts and solids for anions and cations and for bulk δ15 N for multivariate chemometric evaluation. RESULTS: The Ti(III)-based isotope analyses of nitrate in strawberry extracts revealed clear differentiation between organic and conventional production with mean δ18 O and δ15 N values of +18.3 ± 1.2 ‰ and +17.6 ± 1.2 ‰ versus +28.2 ± 4.5 ‰ and +14.9 ± 3.0 ‰, respectively. The δ15 N of strawberry dry mass differed slightly (+3.0 ± 1.4 ‰ versus +4.0 ± 1.4 ‰) between organic and conventional samples, respectively. Chemometric analyses of nitrate isotopes and extract chemistry revealed that the δ18 O of nitrate along with δ15 N and Ca2+ fully differentiated organic from conventional strawberry production. CONCLUSIONS: Our results show the Ti(III) reduction method provides a new low-cost and rapid analytical method to facilitate compound-specific δ15 N and δ18 O isotope analyses of nitrate in selected fruit types, and likely other food products, for the purposes of assessing nitrate fertilization practices of organic versus conventional production claims and to support authenticity investigations.

Neurophysiological correlates of dual tasking in people with Parkinson's disease and freezing of gait.

Freezing of gait in people with Parkinson's disease (PwP) is associated with executive dysfunction and motor preparation deficits. We have recently shown that electrophysiological markers of motor preparation, rather than decision-making, differentiate PwP with freezing of gait (FOG +) and without (FOG -) while sitting. To examine the effect of locomotion on these results, we measured behavioural and electrophysiological responses in PwP with and without FOG during a target response time task while sitting (single-task) and stepping-in-place (dual-task). Behavioural and electroencephalographic data were acquired from 18 PwP (eight FOG +) and seven young controls performing the task while sitting and stepping-in-place. FOG + had slower response times while stepping compared with sitting. However, response times were significantly faster while stepping compared with sitting for controls. Electrophysiological responses showed no difference in decision-making potentials (centroparietal positivity) between groups or conditions but there were differences in neurophysiological markers of response inhibition (N2) and motor preparation (lateralized readiness potential, LRP) in FOG + while performing a dual-task. This suggests that the addition of a second complex motor task (stepping-in-place) impacts automatic allocation of resources in FOG +, resulting in delayed response times. The impact of locomotion on the generation of the N2 and LRP potentials, particularly in freezers, indirectly implies that these functions compete with locomotion for resources. In the setting of multiple complex tasks or cognitive impairment, severe motor dysfunction may result, leading to freezing of gait.

Rhizobium leguminosarum bv. trifolii NodD2 Enhances Competitive Nodule Colonization in the Clover-Rhizobium Symbiosis.

Establishment of the symbiotic relationship that develops between rhizobia and their legume hosts is contingent upon an interkingdom signal exchange. In response to host legume flavonoids, NodD proteins from compatible rhizobia activate expression of nodulation genes that produce lipochitin oligosaccharide signaling molecules known as Nod factors. Root nodule formation commences upon legume recognition of compatible Nod factor. Rhizobium leguminosarum was previously considered to contain one copy of nodD; here, we show that some strains of the Trifolium (clover) microsymbiont R. leguminosarum bv. trifolii contain a second copy designated nodD2. nodD2 genes were present in 8 out of 13 strains of R. leguminosarum bv. trifolii, but were absent from the genomes of 16 R. leguminosarum bv. viciae strains. Analysis of single and double nodD1 and nodD2 mutants in R. leguminosarum bv. trifolii strain TA1 revealed that NodD2 was functional and enhanced nodule colonization competitiveness. However, NodD1 showed significantly greater capacity to induce nod gene expression and infection thread formation. Clover species are either annual or perennial and this phenological distinction is rarely crossed by individual R. leguminosarum bv. trifolii microsymbionts for effective symbiosis. Of 13 strains with genome sequences available, 7 of the 8 effective microsymbionts of perennial hosts contained nodD2, whereas the 3 microsymbionts of annual hosts did not. We hypothesize that NodD2 inducer recognition differs from NodD1, and NodD2 functions to enhance competition and effective symbiosis, which may discriminate in favor of perennial hosts.IMPORTANCE Establishment of the rhizobium-legume symbiosis requires a highly specific and complex signal exchange between both participants. Rhizobia perceive legume flavonoid compounds through LysR-type NodD regulators. Often, rhizobia encode multiple copies of nodD, which is one determinant of host specificity. In some species of rhizobia, the presence of multiple copies of NodD extends their symbiotic host-range. Here, we identified and characterized a second copy of nodD present in some strains of the clover microsymbiont Rhizobium leguminosarum bv. trifolii. The second nodD gene contributed to the competitive ability of the strain on white clover, an important forage legume. A screen for strains containing nodD2 could be utilized as one criterion to select strains with enhanced competitive ability for use as inoculants for pasture production.

Parietal neurons encode expected gains in instrumental information.

In natural behavior, animals have access to multiple sources of information, but only a few of these sources are relevant for learning and actions. Beyond choosing an appropriate action, making good decisions entails the ability to choose the relevant information, but fundamental questions remain about the brain's information sampling policies. Recent studies described the neural correlates of seeking information about a reward, but it remains unknown whether, and how, neurons encode choices of instrumental information, in contexts in which the information guides subsequent actions. Here we show that parietal cortical neurons involved in oculomotor decisions encode, before an information sampling saccade, the reduction in uncertainty that the saccade is expected to bring for a subsequent action. These responses were distinct from the neurons' visual and saccadic modulations and from signals of expected reward or reward prediction errors. Therefore, even in an instrumental context when information and reward gains are closely correlated, individual cells encode decision variables that are based on informational factors and can guide the active sampling of action-relevant cues.

Antagonistic Interactions Between Microsaccades and Evidence Accumulation Processes During Decision Formation.

Despite their small size, microsaccades can impede stimulus detections if executed at inopportune times. Although it has been shown that microsaccades evoke both inhibitory and excitatory responses across different visual regions, their impact on the higher-level neural decision processes that bridge sensory responses to action selection has yet to be examined. Here, we show that when human observers monitor stimuli for subtle feature changes, the occurrence of microsaccades long after (up to 800 ms) change onset predicts slower reaction times and this is accounted for by momentary suppression of neural signals at each key stage of decision formation: visual evidence encoding, evidence accumulation, and motor preparation. Our data further reveal that, independent of the timing of the change events, the onset of neural decision formation coincides with a systematic inhibition of microsaccade production, persisting until the perceptual report is executed. Our combined behavioral and neural measures highlight antagonistic interactions between microsaccade occurrence and evidence accumulation during visual decision-making tasks.SIGNIFICANCE STATEMENT When fixating on a location in space, we frequently make tiny eye movements called microsaccades. In the present study, we show that these microsaccades impede our ability to make perceptual decisions about visual stimuli and this impediment specifically occurs via the disruption of several processing levels of the sensorimotor network: the encoding of visual evidence itself, the accumulation of visual evidence toward a response, and effector-selective motor preparation. Furthermore, we show that the production of microsaccades is inhibited during the perceptual decision, possibly as a counteractive measure to mitigate their negative effect on behavior in this context. The combined behavioral and neural measures used in this study provide strong and novel evidence for the interaction of fixational eye movements and the perceptual decision-making process.

Epidermal auxin biosynthesis facilitates rhizobial infection in Lotus japonicus.

Symbiotic nitrogen fixation in legumes requires nodule organogenesis to be coordinated with infection by rhizobia. The plant hormone auxin influences symbiotic infection, but the precise timing of auxin accumulation and the genetic network governing it remain unclear. We used a Lotus japonicus optimised variant of the DII-based auxin accumulation sensor and identified a rapid accumulation of auxin in the epidermis, specifically in the root hair cells. This auxin accumulation occurs in the infected root hairs during rhizobia invasion, while Nod factor application induces this response across a broader range of root hairs. Using the DR5 auxin responsive promoter, we demonstrate that activation of auxin signalling also occurs specifically in infected root hairs. Analysis of root hair transcriptome data identified induction of an auxin biosynthesis gene of the Tryptophan Amino-transferase Related (LjTar1) family following both bacteria inoculation and Nod factor treatment. Genetic analysis showed that both expression of the LjTar1 biosynthesis gene and the auxin response requires Nod factor perception, while common symbiotic pathway transcription factors are only partially required or act redundantly to initiate auxin accumulation. Using a chemical genetics approach, we confirmed that auxin biosynthesis has a functional role in promoting symbiotic infection events in the epidermis.

Sinorhizobium fredii HH103 nolR and nodD2 mutants gain capacity for infection thread invasion of Lotus japonicus Gifu and Lotus burttii.

Sinorhizobium fredii HH103 RifR , a broad-host-range rhizobial strain, forms ineffective nodules with Lotus japonicus but induces nitrogen-fixing nodules in Lotus burttii roots that are infected by intercellular entry. Here we show that HH103 RifR nolR or nodD2 mutants gain the ability to induce infection thread formation and to form nitrogen-fixing nodules in L. japonicus Gifu. Microscopy studies showed that the mode of infection of L. burttii roots by the nodD2 and nolR mutants switched from intercellular entry to infection threads (ITs). In the presence of the isoflavone genistein, both mutants overproduced Nod-factors. Transcriptomic analyses showed that, in the presence of Lotus japonicus Gifu root exudates, genes related to Nod factors production were overexpressed in both mutants in comparison to HH103 RifR . Complementation of the nodD2 and nolR mutants provoked a decrease in Nod-factor production, the incapacity to form nitrogen-fixing nodules with L. japonicus Gifu and restored the intercellular way of infection in L. burttii. Thus, the capacity of S. fredii HH103 RifR nodD2 and nolR mutants to infect L. burttii and L. japonicus Gifu by ITs and fix nitrogen L. japonicus Gifu might be correlated with Nod-factor overproduction, although other bacterial symbiotic signals could also be involved.

The Brassicaceae Family Displays Divergent, Shoot-Skewed NLR Resistance Gene Expression.

Nucleotide-binding site leucine-rich repeat resistance genes (NLRs) allow plants to detect microbial effectors. We hypothesized that NLR expression patterns could reflect organ-specific differences in effector challenge and tested this by carrying out a meta-analysis of expression data for 1,235 NLRs from nine plant species. We found stable NLR root/shoot expression ratios within species, suggesting organ-specific hardwiring of NLR expression patterns in anticipation of distinct challenges. Most monocot and dicot plant species preferentially expressed NLRs in roots. In contrast, Brassicaceae species, including oilseed rape (Brassica napus) and the model plant Arabidopsis (Arabidopsis thaliana), were unique in showing NLR expression skewed toward the shoot across multiple phylogenetically distinct groups of NLRs. The Brassicaceae are also outliers in the sense that they have lost the common symbiosis signaling pathway, which enables intracellular infection by root symbionts. While it is unclear if these two events are related, the NLR expression shift identified here suggests that the Brassicaceae may have evolved unique pattern-recognition receptors and antimicrobial root metabolites to substitute for NLR protection. Such innovations in root protection could potentially be exploited in crop rotation schemes or for enhancing root defense systems of non-Brassicaceae crops.

Dynamics of Ethylene Production in Response to Compatible Nod Factor.

Establishment of symbiotic nitrogen-fixation in legumes is regulated by the plant hormone ethylene, but it has remained unclear whether and how its biosynthesis is regulated by the symbiotic pathway. We established a sensitive ethylene detection system for Lotus japonicus and found that ethylene production increased as early as 6 hours after inoculation with Mesorhizobium loti This ethylene response was dependent on Nod factor production by compatible rhizobia. Analyses of nodulation mutants showed that perception of Nod factor was required for ethylene emission, while downstream transcription factors including CYCLOPS, NIN, and ERN1 were not required for this response. Activation of the nodulation signaling pathway in spontaneously nodulating mutants was also sufficient to elevate ethylene production. Ethylene signaling is controlled by EIN2, which is duplicated in L. japonicus We obtained a L. japonicus Ljein2a Ljein2b double mutant that exhibits complete ethylene insensitivity and confirms that these two genes act redundantly in ethylene signaling. Consistent with this redundancy, both LjEin2a and LjEin2b are required for negative regulation of nodulation and Ljein2a Ljein2b double mutants are hypernodulating and hyperinfected. We also identified an unexpected role for ethylene in the onset of nitrogen fixation, with the Ljein2a Ljein2b double mutant showing severely reduced nitrogen fixation. These results demonstrate that ethylene production is an early and sustained nodulation response that acts at multiple stages to regulate infection, nodule organogenesis, and nitrogen fixation in L. japonicus.

Intellectual disability and autism: socioeconomic impacts of informal caring, projected to 2030.

BACKGROUND: Intellectual disability and autism spectrum disorder (ASD) influence the interactions of a person with their environment and generate economic and socioeconomic costs for the person, their family and society. AIMS: To estimate costs of lost workforce participation due to informal caring for people with intellectual disability or autism spectrum disorders by estimating lost income to individuals, lost taxation payments to federal government and increased welfare payments. METHOD: We used a microsimulation model based on the Australian Bureau of Statistics' Surveys of Disability, Ageing and Carers (population surveys of people aged 15-64), and projected costs of caring from 2015 in 5-year intervals to 2030. RESULTS: The model estimated that informal carers of people with intellectual disability and/or ASD in Australia had aggregated lost income of AU$310 million, lost taxation of AU$100 million and increased welfare payments of AU$204 million in 2015. These are projected to increase to AU$432 million, AU$129 million and AU$254 million for income, taxation, and welfare respectively by 2030. The income gap of carers for people with intellectual disability and/or ASD is estimated to increase by 2030, meaning more financial stress for carers. CONCLUSIONS: Informal carers of people with intellectual disability and/or ASD experience significant loss of income, leading to increased welfare payments and reduced taxation revenue for governments; these are all projected to increase. Strategic policies supporting informal carers wishing to return to work could improve the financial and psychological impact of having a family member with intellectual disability and/or ASD. DECLARATION OF INTEREST: None.

The indirect costs of ischemic heart disease through lost productive life years for Australia from 2015 to 2030: results from a microsimulation model.

BACKGROUND: Most studies measure the impact of ischemic heart disease (IHD) on individuals using quality of life metrics such as disability-adjusted life-years (DALYs); however, IHD also has an enormous impact on productive life years (PLYs). The objective of this study was to project the indirect costs of IHD resulting from lost PLYs to older Australian workers (45-64 years), government, and society 2015-2030. METHODS: Nationally representative data from the Surveys of Disability, Ageing and Carers (2003, 2009) were used to develop the base population in the microsimulation model (Health&WealthMOD2030), which integrated data from established microsimulation models (STINMOD, APPSIM), Treasury's population and workforce projections, and chronic conditions trends. RESULTS: We projected that 6700 people aged 45-64 were out of the labour force due to IHD in 2015, increasing to 8100 in 2030 (21 increase). National costs consisted of a loss of AU$273 (US$263) million in income for people with IHD in 2015, increasing to AU$443 ($US426) million (62% increase). For the government, extra welfare payments increased from AU$106 (US$102) million in 2015 to AU$143 (US$138) million in 2030 (35% increase); and lost income tax revenue increased from AU$74 (US$71) million in 2015 to AU$117 (US$113) million in 2030 (58% increase). A loss of AU$785 (US$755) million in GDP was projected for 2015, increasing to AU$1125 (US$1082) million in 2030. CONCLUSIONS: Significant costs of IHD through lost productivity are incurred by individuals, the government, and society. The benefits of IHD interventions include not only improved health but also potentially economic benefits as workforce capacity.

Rehabilitation of emergent awareness of errors post traumatic brain injury: A pilot intervention.

Impaired awareness of errors is common following traumatic brain injury (TBI) and can be a barrier to successful rehabilitation. The objective of this study was to develop and evaluate a computer-based intervention programme aimed at improving error awareness in individuals with TBI. A further aim was to explore its effects on metacognitive awareness and variability of performance. Participants were 11 individuals with TBI and impaired error awareness who performed a sustained attention task twice-weekly for four weeks. The intervention consisted of audio-visual feedback-on-errors during the sustained attention task. Six participants received audio-visual feedback-on-error, five did not receive feedback. Emergent and metacognitive awareness were measured pre- and post-intervention. Between-groups comparisons of emergent awareness from pre- to post-intervention showed that audio-visual feedback-on-error improved emergent awareness compared to no feedback-on-error. Some changes in metacognitive awareness of executive behaviours as a result of feedback were observed. Audio-visual feedback-on-error improved emergent awareness in individuals with TBI following a four-week/eight-session intervention. This improvement was not observed in the no-feedback group. This pilot intervention is not a stand-alone treatment but it has potential to be usefully incorporated into cognitive or clinical rehabilitation programmes to improve emergent awareness.

Neural Signature of Value-Based Sensorimotor Prioritization in Humans.

In situations in which impending sensory events demand fast action choices, we must be ready to prioritize higher-value courses of action to avoid missed opportunities. When such a situation first presents itself, stimulus-action contingencies and their relative value must be encoded to establish a value-biased state of preparation for an impending sensorimotor decision. Here, we sought to identify neurophysiological signatures of such processes in the human brain (both female and male). We devised a task requiring fast action choices based on the discrimination of a simple visual cue in which the differently valued sensory alternatives were presented 750-800 ms before as peripheral "targets" that specified the stimulus-action mapping for the upcoming decision. In response to the targets, we identified a discrete, transient, spatially selective signal in the event-related potential (ERP), which scaled with relative value and strongly predicted the degree of behavioral bias in the upcoming decision both across and within subjects. This signal is not compatible with any hitherto known ERP signature of spatial selection and also bears novel distinctions with respect to characterizations of value-sensitive, spatially selective activity found in sensorimotor areas of nonhuman primates. Specifically, a series of follow-up experiments revealed that the signal was reliably invoked regardless of response laterality, response modality, sensory feature, and reward valence. It was absent, however, when the response deadline was relaxed and the strategic need for biasing removed. Therefore, more than passively representing value or salience, the signal appears to play a versatile and active role in adaptive sensorimotor prioritization.SIGNIFICANCE STATEMENT In many situations such as fast-moving sports, we must be ready to act fast in response to sensory events and, in our preparation, prioritize courses of action that lead to greater rewards. Although behavioral effects of value biases in sensorimotor decision making have been widely studied, little is known about the neural processes that set these biases in place beforehand. Here, we report the discovery of a transient, spatially selective neural signal in humans that encodes the relative value of competing decision alternatives and strongly predicts behavioral value biases in decisions made ∼500 ms later. Follow-up manipulations of value differential, reward valence, response modality, sensory features, and time constraints establish that the signal reflects an active, feature- and effector-general preparatory mechanism for value-based prioritization.

Visuospatial Asymmetries Arise from Differences in the Onset Time of Perceptual Evidence Accumulation.

Healthy subjects tend to exhibit a bias of visual attention whereby left hemifield stimuli are processed more quickly and accurately than stimuli appearing in the right hemifield. It has long been held that this phenomenon arises from the dominant role of the right cerebral hemisphere in regulating attention. However, methods that would enable more precise understanding of the mechanisms underpinning visuospatial bias have remained elusive. We sought to finely trace the temporal evolution of spatial biases by leveraging a novel bilateral dot motion detection paradigm. In combination with electroencephalography, this paradigm enables researchers to isolate discrete neural signals reflecting the key neural processes needed for making these detection decisions. These include signals for spatial attention, early target selection, evidence accumulation, and motor preparation. Using this method, we established that three key neural markers accounted for unique between-subject variation in visuospatial bias: hemispheric asymmetry in posterior α power measured before target onset, which is related to the distribution of preparatory attention across the visual field; asymmetry in the peak latency of the early N2c target-selection signal; and, finally, asymmetry in the onset time of the subsequent neural evidence-accumulation process with earlier onsets for left hemifield targets. Our development of a single paradigm to dissociate distinct processing components that track the temporal evolution of spatial biases not only advances our understanding of the neural mechanisms underpinning normal visuospatial attention bias, but may also in the future aid differential diagnoses in disorders of spatial attention.SIGNIFICANCE STATEMENT The significance of this research is twofold. First, it shows that individual differences in how humans direct their attention between left and right space reflects physiological differences in how early the brain starts to accumulate evidence for the existence of a visual target. Second, the novel methods developed here may have particular relevance to disorders of attention, such as unilateral spatial neglect. In the case of spatial neglect, pathological inattention to left space could have multiple underlying causes, including biased attention, impaired decision formation, or a motor deficit related to one side of space. Our development of a single paradigm to dissociate each of these components may aid in supporting more precise differential diagnosis in such heterogeneous disorders.