Action boosts episodic memory encoding in humans via engagement of a noradrenergic system

SUMMARYWe are constantly interacting with our environment whilst we encode memories. However, how actions influence memory formation remains poorly understood. Goal-directed movement engages the locus coeruleus (LC), the main source of noradrenaline in the brain. Noradrenaline is also known to enhance episodic encoding, suggesting that action could improve memory via LC engagement. Here we demonstrate, across seven experiments, that action (Go-response) enhances episodic encoding for stimuli unrelated to the action itself, compared to action inhibition (NoGo). Supporting a noradrenergic mechanism underlying this enhancement, functional magnetic resonance imaging, and pupil diameter as a proxy measure for LC-noradrenaline transmission, indicate increased encoding-related LC activity during action. A final experiment confirmed a novel prediction derived from these data that emotionally aversive stimuli, which recruit the noradrenergic system, modulate the mnemonic advantage conferred by Go-responses relative to neutral stimuli. We therefore provide converging evidence that action boosts episodic memory encoding via a noradrenergic mechanism.

Antipsychotic drugs for psychosis and agitation in dementia: efficacy, safety, and a possible noradrenergic mechanism of action

The first patient described by Alzheimer in 1907 had both progressive cognitive deterioration and prominent comorbid signs and symptoms of psychosis and agitation (Alzheimer, 1907, 1987). In this editorial, we use “psychosis” to denote delusions and hallucinations and “agitation” to denote irritability, aggression, pressured motor activity, and active resistance to necessary care. Although advances have been made in the treatment of these non-cognitive symptoms, these psychosis and agitation symptoms continued to be burdensome and costly for dementia patients, caregivers, and society. Among the pharmacologic treatments available for psychosis and agitation, antipsychotic drugs are the drug class most consistently demonstrated effective for psychosis and agitation in dementia (Lyketsos et al., 2006; APA Work Group on Alzheimer's Disease and Other Dementias et al., 2007). These are widely prescribed for these behavioral problems, but their use remains controversial and their mechanism of action unclear.