On the role of serotonin and effort in voluntary attention: evidence of genetic variation in N1 modulation.

Ascending serotonergic projections from the raphe nuclei to frontal brain areas and the dense distribution of receptor and transporter sites in prefrontal and sensory regions support the idea that serotonin exerts influence on cognitive functioning. Indeed, growing evidence suggests serotonin to be an important factor in learning and memory; however, its precise role in executive processes particularly in voluntary attention is less clear. Event-related EEG studies showed the N1 potential to predict top-down attention allocation and implicated the auditory N1 in central serotonergic activity. Dipole analyses and single-trial coupling of EEG and fMRI revealed N1 sources in the primary auditory cortex and in the anterior cingulate. In the present study, amplitude variation of the event-related N1 potential was investigated on 72 healthy subjects while performing an auditory novelty oddball paradigm to tap top-down and bottom-up attention allocation. Possible serotonergic effects on voluntary attention were analyzed using allele variants of a functional polymorphism (5-HTTLPR) of the gene encoding the serotonin transporter, a key regulator of serotonergic neurotransmission. Because mental effort has been related to top-down attention and N1 modulation, a measure of stable individual differences in cognitive effort was included. The main result was a strong interaction of 5-HTTLPR and cognitive effort on target N1 amplitude. Greater target-related attention allocation was evident in those carriers of the 5-HTTLPR s-allele who described themselves as being more engaged in effortful processing. We suggest that the observed interaction mirrors the interplay between effort-mediated top-down attention by the ACC and serotonergic adjustment on attentional systems.