Decisions about noisy stimuli are widely understood to be made by accumulating evidence up to a decision bound that can be adjusted according to task demands. However, relatively little is known about how such mechanisms operate in continuous monitoring contexts requiring intermittent target detection. Here, we examined neural decision processes underlying detection of 1 s coherence targets within continuous random dot motion, and how they are adjusted across contexts with weak, strong, or randomly mixed weak/strong targets. Our prediction was that decision bounds would be set lower when weak targets are more prevalent. Behavioural hit and false alarm rate patterns were consistent with this, and were well captured by a bound-adjustable leaky accumulator model. However, beta-band EEG signatures of motor preparation contradicted this, instead indicating lower bounds in the strong-target context. We thus tested two alternative models in which decision-bound dynamics were constrained directly by beta measurements, respectively, featuring leaky accumulation with adjustable leak, and non-leaky accumulation of evidence referenced to an adjustable sensory-level criterion. We found that the latter model best explained both behaviour and neural dynamics, highlighting novel means of decision policy regulation and the value of neurally informed modelling.

A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A hallmark of ALS/FTD pathology is the presence of dipeptide repeat (DPR) proteins, produced from both sense GGGGCC (poly-GA, poly-GP, poly-GR) and antisense CCCCGG (poly-PR, poly-PG, poly-PA) transcripts. Translation of sense DPRs, such as poly-GA and poly-GR, depends on non-canonical (non-AUG) initiation codons. Here, we provide evidence for canonical AUG-dependent translation of two antisense DPRs, poly-PR and poly-PG. A single AUG is required for synthesis of poly-PR, one of the most toxic DPRs. Unexpectedly, we found redundancy between three AUG codons necessary for poly-PG translation. Further, the eukaryotic translation initiation factor 2D (EIF2D), which was previously implicated in sense DPR synthesis, is not required for AUG-dependent poly-PR or poly-PG translation, suggesting that distinct translation initiation factors control DPR synthesis from sense and antisense transcripts. Our findings on DPR synthesis from the C9ORF72 locus may be broadly applicable to many other nucleotide repeat expansion disorders.