Novelty exposure and the upregulation of the noradrenergic (NA) system have been suggested as crucial for developing cognitive reserve and resilience against neurodegeneration. Openness to experience (OE), a personality trait associated with interest in novel experiences, may play a key role in facilitating this process. High-OE individuals tend to be more curious and encounter a wider range of novel stimuli throughout their lifespan. To investigate the relationship between OE and the main core of the NA system, the locus coeruleus (LC), as well as its potential mediation of IQ—a measure of cognitive reserve—MRI structural analyses were conducted on 135 healthy young adults. Compared with other neuromodulators' seeds, such as dorsal and median raphe-5-HT, ventral tegmental area-DA-, and nucleus basalis of Meynert-Ach-, the results indicated that higher LC signal intensity correlated with greater OE and IQ. Furthermore, mediation analyses revealed that only the LC played a mediating role between OE and IQ. These findings shed light on the neurobiology of personality and emphasize the importance of LC-NA system integrity in a novelty-seeking behavior. They provide a psychobiological explanation for how OE expression can contribute to the maintenance of the NA system, enhancing cognitive reserve and resilience against neurodegeneration.

Recent behavioral modeling and pupillometry studies suggest that neuromodulatory arousal systems play a role in regulating decision formation but neurophysiological support for these observations is lacking. We employed a randomized, double-blinded, placebo-controlled, crossover design to probe the impact of pharmacological enhancement of catecholamine levels on perceptual decision-making. Catecholamine levels were manipulated using the clinically relevant drugs methylphenidate and atomoxetine, and their effects were compared with those of citalopram and placebo. Participants performed a classic EEG oddball paradigm that elicits the P3b, a centro-parietal potential that has been shown to trace evidence accumulation, under each of the four drug conditions. We found that methylphenidate and atomoxetine administration shortened RTs to the oddball targets. The neural basis of this behavioral effect was an earlier P3b peak latency, driven specifically by an increase in its buildup rate without any change in its time of onset or peak amplitude. This study provides neurophysiological evidence for the catecholaminergic enhancement of a discrete aspect of human decision-making, that is, evidence accumulation. Our results also support theoretical accounts suggesting that catecholamines may enhance cognition via increases in neural gain.

The ability to sustain attention is integral to healthy cognition in aging. The right PFC (rPFC) is critical for maintaining high levels of attentional focus. Whether plasticity of this region can be harnessed to support sustained attention in older adults is unknown. We used transcranial direct current stimulation to increase cortical excitability of the rPFC, while monitoring behavioral and electrophysiological markers of sustained attention in older adults with suboptimal sustained attention capacity. During rPFC transcranial direct current stimulation, fewer lapses of attention occurred and electroencephalography signals of frontal engagement and early visual attention were enhanced. To further verify these results, we repeated the experiment in an independent cohort of cognitively typical older adults using a different sustained attention paradigm. Again, prefrontal stimulation was associated with fewer attentional lapses. These experiments suggest the rPFC can be manipulated in later years to increase top–down modulation over early sensory processing and improve sustained attention performance. This holds valuable information for the development of neurorehabilitation protocols to ameliorate age-related deficits in this capacity.