Confidence and central tendency in perceptual judgment

Stimulated cells and cancer cells have widespread shortening of mRNA 3’-untranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells’ migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

When facing uncertainty, adaptive behavioral strategies demand that the brain performs probabilistic computations. In this probabilistic framework, the notion of certainty and confidence would appear to be closely related, so much so that it is tempting to conclude that these two concepts are one and the same. We argue that there are computational reasons to distinguish between these two concepts. Specifically, we propose that confidence should be defined as the probability that a decision or a proposition, overt or covert, is correct given the evidence, a critical quantity in complex sequential decisions. We suggest that the term certainty should be reserved to refer to the encoding of all other probability distributions over sensory and cognitive variables. We also discuss strategies for studying the neural codes for confidence and certainty and argue that clear definitions of neural codes are essential to understanding the relative contributions of various cortical areas to decision making.