Beyond bias: A registered examination of the validity of using line bisection to measure non-lateralised attention.

Line bisection is a task widely used to assess lateral asymmetries of attention, in which participants are asked to mark the midpoint of a horizontal line. The directional bisection error (DBE) from the objective midpoint of the line is the traditional measure of performance. However, an alternative method of studying the bisection behaviour, the endpoint weightings method, has been proposed. This method produces two measures of performance: endpoint weightings bias (EWB) and endpoint weightings sum (EWS). While EWB measures attentional asymmetry, it has been suggested that EWS quantifies the total (non-lateralised) attention allocated to the task. If EWS provides a valid index of non-lateralised attention, then changes in tonic and phasic arousal should systematically affect EWS. In this article, we formally tested this prediction, using time on task to manipulate tonic arousal and unpredictable auditory tones, presented simultaneously with line stimuli, to manipulate phasic arousal. Our registered analyses revealed that neither of our manipulations for tonic or phasic arousal significantly influenced EWS. Therefore, the null hypotheses cannot be rejected. An exploratory analysis of all trials and conditions revealed a significant reduction in EWS with time spent on task. However, the lack of any significant effect of the alerting tone on EWS suggests that EWS may not be a valid measure of generalised attention to the task.

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus.

OBJECTIVES: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. METHODS: We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer's disease, Huntington's disease, Parkinson's disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. RESULTS: From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. DISCUSSION: For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs.