Levodopa enhances explicit new-word learning in healthy adults: a preliminary study.

OBJECTIVE: While the role of dopamine in modulating executive function, working memory and associative learning has been established; its role in word learning and language processing more generally is not clear. This preliminary study investigated the impact of increased synaptic dopamine levels on new-word learning ability in healthy young adults using an explicit learning paradigm. METHOD: A double-blind, placebo-controlled, between-groups design was used. Participants completed five learning sessions over 1 week with levodopa or placebo administered at each session (five doses, 100 mg). Each session involved a study phase followed by a test phase. Test phases involved recall and recognition tests of the new (non-word) names previously paired with unfamiliar objects (half with semantic descriptions) during the study phase. RESULTS: The levodopa group showed superior recall accuracy for new words over five learning sessions compared with the placebo group and better recognition accuracy at a 1-month follow-up for words learnt with a semantic description. CONCLUSIONS: These findings suggest that dopamine boosts initial lexical acquisition and enhances longer-term consolidation of words learnt with semantic information, consistent with dopaminergic enhancement of semantic salience.

Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study.

BACKGROUND: Sepsis is defined as dysregulated host response to infection that leads to life-threatening organ dysfunction. Biomarkers characterising the dysregulated host response in sepsis are lacking. We aimed to develop host gene expression signatures to predict organ dysfunction in children with bacterial or viral infection. METHODS: This cohort study was done in emergency departments and intensive care units of four hospitals in Queensland, Australia, and recruited children aged 1 month to 17 years who, upon admission, underwent a diagnostic test, including blood cultures, for suspected sepsis. Whole-blood RNA sequencing of blood was performed with Illumina NovaSeq (San Diego, CA, USA). Samples with completed phenotyping, monitoring, and RNA extraction by March 31, 2020, were included in the discovery cohort; samples collected or completed thereafter and by Oct 27, 2021, constituted the Rapid Paediatric Infection Diagnosis in Sepsis (RAPIDS) internal validation cohort. An external validation cohort was assembled from RNA sequencing gene expression count data from the observational European Childhood Life-threatening Infectious Disease Study (EUCLIDS), which recruited children with severe infection in nine European countries between 2012 and 2016. Feature selection approaches were applied to derive novel gene signatures for disease class (bacterial vs viral infection) and disease severity (presence vs absence of organ dysfunction 24 h post-sampling). The primary endpoint was the presence of organ dysfunction 24 h after blood sampling in the presence of confirmed bacterial versus viral infection. Gene signature performance is reported as area under the receiver operating characteristic curves (AUCs) and 95% CI. FINDINGS: Between Sept 25, 2017, and Oct 27, 2021, 907 patients were enrolled. Blood samples from 595 patients were included in the discovery cohort, and samples from 312 children were included in the RAPIDS validation cohort. We derived a ten-gene disease class signature that achieved an AUC of 94·1% (95% CI 90·6-97·7) in distinguishing bacterial from viral infections in the RAPIDS validation cohort. A ten-gene disease severity signature achieved an AUC of 82·2% (95% CI 76·3-88·1) in predicting organ dysfunction within 24 h of sampling in the RAPIDS validation cohort. Used in tandem, the disease class and disease severity signatures predicted organ dysfunction within 24 h of sampling with an AUC of 90·5% (95% CI 83·3-97·6) for patients with predicted bacterial infection and 94·7% (87·8-100·0) for patients with predicted viral infection. In the external EUCLIDS validation dataset (n=362), the disease class and disease severity predicted organ dysfunction at time of sampling with an AUC of 70·1% (95% CI 44·1-96·2) for patients with predicted bacterial infection and 69·6% (53·1-86·0) for patients with predicted viral infection. INTERPRETATION: In children evaluated for sepsis, novel host transcriptomic signatures specific for bacterial and viral infection can identify dysregulated host response leading to organ dysfunction. FUNDING: Australian Government Medical Research Future Fund Genomic Health Futures Mission, Children's Hospital Foundation Queensland, Brisbane Diamantina Health Partners, Emergency Medicine Foundation, Gold Coast Hospital Foundation, Far North Queensland Foundation, Townsville Hospital and Health Services SERTA Grant, and Australian Infectious Diseases Research Centre.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.

Neural mechanisms underlying the facilitation of naming in aphasia using a semantic task: an fMRI study.

BACKGROUND: Previous attempts to investigate the effects of semantic tasks on picture naming in both healthy controls and people with aphasia have typically been confounded by inclusion of the phonological word form of the target item. As a result, it is difficult to isolate any facilitatory effects of a semantically-focused task to either lexical-semantic or phonological processing. This functional magnetic resonance imaging (fMRI) study examined the neurological mechanisms underlying short-term (within minutes) and long-term (within days) facilitation of naming from a semantic task that did not include the phonological word form, in both participants with aphasia and age-matched controls. RESULTS: Behavioral results showed that a semantic task that did not include the phonological word form can successfully facilitate subsequent picture naming in both healthy controls and individuals with aphasia. The whole brain neuroimaging results for control participants identified a repetition enhancement effect in the short-term, with modulation of activity found in regions that have not traditionally been associated with semantic processing, such as the right lingual gyrus (extending to the precuneus) and the left inferior occipital gyrus (extending to the fusiform gyrus). In contrast, the participants with aphasia showed significant differences in activation over both the short- and the long-term for facilitated items, predominantly within either left hemisphere regions linked to semantic processing or their right hemisphere homologues. CONCLUSIONS: For control participants in this study, the short-lived facilitation effects of a prior semantic task that did not include the phonological word form were primarily driven by object priming and episodic memory mechanisms. However, facilitation effects appeared to engage a predominantly semantic network in participants with aphasia over both the short- and the long-term. The findings of the present study also suggest that right hemisphere involvement may be supportive rather than maladaptive, and that a large distributed perisylvian network in both cerebral hemispheres supports the facilitation of naming in individuals with aphasia.

An fMRI investigation of the effects of attempted naming on word retrieval in aphasia.

In healthy controls, picture naming performance can be facilitated by a single prior exposure to the same picture ("priming"). This priming phenomenon is utilized in the treatment of aphasia, which often includes repeated picture naming as part of a therapeutic task. The current study sought to determine whether single and/or multiple exposures facilitate subsequent naming in aphasia and whether such facilitatory effects act through normal priming mechanisms. A functional magnetic resonance imaging paradigm was employed to explore the beneficial effects of attempted naming in two individuals with aphasia and a control group. The timing and number of prior exposures was manipulated, with investigation of both short-term effects (single prior exposure over a period of minutes) and long-term effects (multiple presentations over a period of days). Following attempted naming, both short-term and long-term facilitated items showed improvement for controls, while only the long-term condition showed benefits at a behavioral level for the participants with aphasia. At a neural level, effects of long-term facilitation were noted in the left precuneus for one participant with aphasia, a result also identified for the equivalent contrast in controls. It appears that multiple attempts are required to improve naming performance in the presence of anomia and that for some individuals with aphasia the source of facilitation may be similar to unimpaired mechanisms engaged outside the language network.

Neuroimaging the short- and long-term effects of repeated picture naming in healthy older adults.

Repeated attempts to name pictures can improve subsequent naming for aphasic individuals with anomia, however, the neurocognitive mechanisms responsible for such improvements are unknown. This study investigated repeated picture naming in healthy older adults over a period of minutes (short-term) after one repetition and a period of days (long-term) after multiple repetitions. Compared to unprimed pictures, both repeated conditions showed faster naming latencies with the fastest latencies evident for the short-term condition. Neuroimaging results identified repetition suppression effects across three left inferior frontal gyrus regions of interest: for both the short- and long-term conditions in the pars orbitalis, and for long-term items in the pars triangularis and pars opercularis regions. The whole brain analysis also showed a repetition suppression effect in bilateral pars triangularis regions for the long-term condition. These findings within the inferior frontal gyrus suggest that effects of repeated naming may be driven by a mapping mechanism across multiple levels of representation, possibly reflecting different levels of learning, and lend support to the idea that processing may be hierarchically organised in the left inferior frontal gyrus. The whole brain analysis also revealed repetition suppression for the long-term condition within the posterior portion of bilateral inferior temporal gyri, which may reflect attenuation of integration processes within this region following the learning of task-relevant information.

Facilitation of naming in aphasia with auditory repetition: an investigation of neurocognitive mechanisms.

Prior phonological processing can enhance subsequent picture naming performance in individuals with aphasia, yet the neurocognitive mechanisms underlying this effect and its longevity are unknown. This study used functional magnetic resonance imaging to examine the short-term (within minutes) and long-term (within days) facilitation effects from a phonological task in both participants with aphasia and age-matched controls. Results for control participants suggested that long-term facilitation of subsequent picture naming may be driven by a strengthening of semantic-phonological connections, while semantic and object recognition mechanisms underlie more short-term effects. All participants with aphasia significantly improved in naming accuracy following both short- and long-term facilitation. A descriptive comparison of the neuroimaging results identified different patterns of activation for each individual with aphasia. The exclusive engagement of a left hemisphere phonological network underlying facilitation was not revealed. The findings suggest that improved naming in aphasia with phonological tasks may be supported by changes in right hemisphere activity in some individuals and reveal the potential contribution of the cerebellum to improved naming following phonological facilitation. Conclusions must be interpreted with caution, however, due to the comparison of corrected group control results to that of individual participants with aphasia, which were not corrected for multiple comparisons.