New research from MIT reports that the abilities to curb impulses and to ignore distractions are independent but ultimately controlled by the same area of the brain.

You won’t get far in life without the ability to pay attention to and focus on what you’re doing. So if you’re having a hard time doing that, at least now you know what’s to blame — the locus coeruleus (LC). According to a new study, norepinephrine-producing neurons in this brain region control the areas of the prefrontal cortex that allow us to focus,  ignore distractions or curb impulses.

Eyes on the prize

“Our results demonstrate a fundamental causal role of LC neuronal activation in the implementation of attentional control by the selective modulation of neural activity in its target areas,” the authors write.

The role norepinephrine-producing LC neurons might have in controlling attention and focus in mammals has been hinted at in the past, but the evidence has always been correlative at best. The team’s findings establish a cause-effect relationship between the two, after they used optogenetics to activate them specifically in mice engaged in three attentional control tasks. This in turn impacted the mice’s performance “immediately and reliably”.

The results could help us better understand and treat disorders that impact attention control or either of its two components — such as attention deficit and hyperactivity disorder (ADHD). Patients with ADHD are both easily distracted and prone to impulsive behavior, but in many cases, one of these components is more heavily expressed. Lead author Andrea Bari explains that they may also help in understanding the LC’s role in anxiety, as the stimulation they administered to the mice during the experiment seemed to lower their anxiety levels.

After engineering the mice’s LC neurons to respond with activity to different colors of light, the team tested what their activation actually does. First, they had the animals wait seven seconds, after which a half-second signal light indicated one of two portals they should go through to find a treat. Mice whose LC activity was stimulated performed the task correctly more often and made fewer premature moves than when not manipulated. Mice whose LC neurons were inhibited performed tasks incorrectly (i.e. they missed the signal) and made more premature moves.

The second experiment involved a three-second signal light identifying the correct portal, which was preceded by a “cue flash”. Sometimes that cue would be on the opposite side, sometimes be in the middle and sometimes be on the correct side. LC stimulation helped improve the performance of the mice involved and made them less impulsive — on the other hand, LC inhibition reduced their correctness and made them more impulsive. Inhibited mice also showed much greater variations in reaction time because they were easily distracted by the cue. They reacted much slower than average when the cue was on the wrong side, and faster than average when the cue was on the correct side.

In the third task, the mice were sometimes presented with constant distraction by (irrelevant) lights while waiting for a three-second signal showing where the food is. The results reproduced previous findings, with one key exception: in cases where these distractor lights weren’t on, inhibited-LC mice did not lapse in performing the task correctly (they only had issues when the distracting lights were turned on).

Finally, based on previous research, the team also controlled for LC activity and norepinephrine release in two brain areas known as the dorsomedial PFC (dmPFC) and the ventrolateral orbitofrontal cortex (vlOFC), where the LC connects to the front area of the brain. Stimulating the LC connections into dmPFC increased correct performance but did not reduce premature responses. Stimulating those in the vlOFC did not improve correct performance but did reduce premature responses.

“Here we have applied behavioral, optogenetic, and neural circuit genetic techniques [to] demonstrate a causal link between temporal-specific LC norepinephrine modulation and attentional control,” the authors wrote. “Our results reveal that the attentional control of behavior is modulated by the synergistic effects of two dissociable coeruleo-cortical pathways, with LC projections to dmPFC enhancing attention and LC projections to vlOFC reducing impulsivity.”

The paper has been published in the journal Proceedings of the National Academy of Sciences (PNAS).