Nicotine Modulates Reorienting of Visuospatial Attention and Neural Activity in Human Parietal Cortex

Abstract

Prior studies in animals and humans indicate that reorienting of visuospatial attention is modulated by the cholinergic agonist nicotine. We have previously identified neural correlates of alerting and reorienting attention in humans and found that the parietal cortex is specifically involved in reorienting. This study investigates whether the alerting and reorienting systems, especially in the parietal cortex, are modulated by nicotine. We used event-related functional magnetic resonance imaging (fMRI) and studied 15 nonsmoking volunteers under placebo and nicotine (NICORETTE s polacrilex gum 1 and 2 mg). Subjects performed a cued target detection task with four different types of randomly intermixed trials (no, neutral, valid, and invalid cue trials). Alerting was captured by comparing BOLD activity and reaction times (RTs) in neutrally cued trials with no cue trials. Reorienting was isolated by comparing invalidly with validly cued trials. On the behavioral level, nicotine affected reorienting of attention by speeding RTs in invalidly cued trials; alerting was not affected by nicotine. Neurally, however, nicotine modulated both attentional systems. Pharmacologic effects on alerting-related brain activity were mainly evident as modulation of BOLD responses in the right angular gyrus and right middle frontal gyrus due to a reduction of neural activity in no cue trials. In the reorienting system, effects of nicotine were mainly evident in the left intraparietal sulcus and precuneus and due to a reduction of neural activity in invalidly cued trials. We conclude that nicotine enhances reorienting of attention in visuospatial tasks and that one behavioral correlate of speeded RTs is reduced parietal activity.

Behavioral and Neural Effects of Nicotine on Visuospatial Attentional Reorienting in Non-Smoking Subjects

“…Interestingly, this cognitive modulation of attentional reorienting has been observed in studies using peripheral cue stimuli, which are thought to elicit automatic (exogenous) attentional orienting (Eriksen and Yeh, 1985;Madden, 1992) as well as centrally presented cue stimuli inducing voluntary (endogenous) attention shifts (Jonides, 1980;Riggio and Kirsner, 1997;Vossel et al, 2006). Regarding the pharmacological modulation (ie, the nicotine-induced reduction of the validity effect), existing animal and human studies have employed central predictive (Thiel et al, 2005), peripheral predictive (Witte et al, 1997;Murphy and Klein, 1998;Stewart et al, 2001), as well as non-predictive cues (50% cue validity; Phillips et al, 2000). However, with regard to human subjects, it has been shown that nicotine exerts its effect in paradigms with central predictive but not with peripheral non-predictive cueing suggesting that the top-down information about the cue-target relationship may play an important role in the pharmacological effect.…”

“…We have previously shown that both the manipulation of cholinergic neurotransmission and the manipulation of cue validity modulate reorienting-related brain activity in parietal and temporo-parietal areas (Thiel et al, 2005;Vossel et al, 2006). In particular, in these regions, both nicotinic stimulation and low cue validity reduce neural activity related to attentional reorienting.…”

“…The difference in reaction times (RTs) to invalidly and validly cued targets is termed the 'validity effect' and is used as a behavioral measure for attentional reorienting. Human and animal evidence suggest that nicotine improves reorienting of attention, as it was shown that nicotinic cholinergic stimulation reduces RTs to invalidly cued targets resulting in a reduction of the validity effect (Witte et al, 1997;Murphy and Klein, 1998;Thiel et al, 2005;Phillips et al, 2000;Stewart et al, 2001;see, however, Griesar et al, 2002). Yu and Dayan (2005) recently proposed that the neurotransmitter acetylcholine signals 'expected uncertainty', that is, the degree of unreliability of predictive relationships.…”

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements

“…However, despite this converging evidence of nicotine effects on enhancing neural processing efficiency (Ettinger et al, 2009;Giessing et al, 2006;Thiel et al, 2005;Wylie et al, 2012), it is important to note that other studies have shown nicotine-induced increase of BOLD response in other brain areas combined with improved performance on relatively more demanding tasks (Kumari et al, 2003). Thus, there is likely not a single or consistent neural signature of nicotine;…”

“…For example, reduced cue-related BOLD response in parietal cortex following nicotine administration has been observed in selective attention paradigms (Giessing et al, 2006;Thiel et al, 2005). Connectivity analysis with resting-state fMRI has revealed more efficient information transfer with a single dose of nicotine (Wylie et al, 2012).…”