A genetic simultaneous MR-PET-EEG/EMG study on the effects of nicotine on early attention processing in smokers and non-smokers

Nicotine has been shown to improve cognition function especially with regard to early attention processing. One potential mechanism involved in the influence of nicotine on attention is the interaction between dopamine and nicotine. On the molecular level nicotine leads to a higher firing rate of dopaminergic neurons via nicotinergic acetylcholine receptors (nAChR). The release of dopamine in the striatum signals a new stimulus and influences early attention processes by shifting attention towards the new (more salient) stimulus. Thus the effects of nicotine on early attention processing are modulated by nAChR. Genotypes that code for this receptor type are associated with nicotine dependence and reduced early attention gating and with cerebral attention networks.

We investigate the effects of a variant of the CHRNA4 gene, which codes for nicotinic receptors, on early attention processes in smokers and non-smokers using a startle reflex paradigm. The startle reflex is a protective reflex response (closure of eye lid) towards an exteroceptive stimulus. Auditory, visual or cutaneous stimulus stimuli can be used, here we use an airpuff applied above the clavicle bone. The eye blink response is recorded using electromyography (EMG) electrodes placed below the eyes.

Our previous work has shown that nicotine effects can be modeled by combining electrophysiology and fMRI (Warbrick et al., 2012) and that the startle reflex can be investigated by combing electrophysiology and fMRI (Neuner et al., 2010). In addition we have established that simultaneous MR-PET-EEG can be a valuable tool for investigating complex concepts such as this (for a review see Shah et al., 2013). In the current study we use simultaneous MR-PET-EEG/EMG to investigate whether: application of nicotine increases dopamine release; dopamine release is associated with changes in early attention gating; nicotine dependent smokers will differ in the effects of nicotine on early attention gating; the nicotinergic acetylcholine receptor genotypes influence early attention gating.

The study is funded by the DFG (Shah, Neuner SH 79/2-2)