Nucleus Basalis Stimulation Enhances Working Memory by Stabilizing Attractor Networks in Prefrontal Cortex

Abstract

The action of acetylcholine in the neocortex is critical for executive function. Cholinergic drugs can improve cognitive function in patient populations and normal adults. How endogenous cholinergic action affects neuronal activity in higher cortical areas is unknown. Here we tested the effects of electrical stimulation of the cortical source of acetylcholine in primates, the Nucleus Basalis of Meynert, on neural activity while monkeys performed working memory tasks.Stimulation delivered in an intermittent fashion improved behavioral performance and increased neuronal activity during the delay period of the task but not to the phasic responses of visual stimuli. Selectivity of neuronal responses broadened, rendering the bump of activity in an attractor network more stable, and filtering distracting stimuli more effectively. These neural results show that acetylcholine has effects on neural activity and selectivity in the prefrontal cortex opposing those of dopamine and fine tuning aggregate neural ensemble activity based on neuromodulatory tone.

Across-Area Synchronization Supports Feature Integration in a Biophysical Network Model of Working Memory

“…Furthermore, encoding and decoding of specific colorlocation associations was accomplished through rate coding. Our hybrid model of rate/temporal coding shares the rich explanatory power of classical ring-attractor models of working memory (Edin et al, 2009;Wei et al, 2012;Wimmer et al, 2014;Almeida et al, 2015;Papadimitriou et al, 2015;Nassar et al, 2018;Bouchacourt and Buschman, 2019;Qi et al, 2019;Barbosa et al, 2020) and derives new predictions that can be tested on multiple levels.…”

“…Working memory, our ability to hold information in mind for short time periods, is a hallmark of cognition but is severely limited on several fronts (Ma et al, 2014). Some of its limitations, such as its capacity, precision, or specific quantitative biases have been successfully accounted for by a family of biophysically-constrained models, mostly on the basis of a ring attractor network that maintains memoranda through sustained reverberatory neural activity (activity bumps) (Compte et al, 2000;Edin et al, 2009;Wei et al, 2012;Wimmer et al, 2014;Almeida et al, 2015;Papadimitriou et al, 2015;Nassar et al, 2018;Bouchacourt and Buschman, 2019;Qi et al, 2019;Barbosa et al, 2020). A feature of working memory that constrains the simultaneous storage of several items is the presence of swap errors (Schneegans and Bays, 2019).…”

Across-area synchronization supports feature integration in working memory

“…Furthermore, encoding and decoding of specific color-location associations was accomplished through rate coding. Our hybrid model of rate/temporal coding shares the rich explanatory power of classical ring-attractor models of working memory (Barbosa et al, 2020;Wimmer et al, 2014;Almeida et al, 2015;Qi et al, 2019;Nassar et al, 2018;Papadimitriou et al, 2015;Edin et al, 2009;Wei et al, 2012;Bouchacourt and Buschman, 2019) and derives new predictions that can be tested on multiple levels.…”

“…Working memory, our ability to hold information in mind for short time periods, is a hallmark of cognition but is severely limited on several fronts (Ma et al, 2014). Some of its limitations, such as its capacity, precision, or specific quantitative biases have been successfully accounted for by a family of biophysically-constrained models, mostly on the basis of a ring attractor network that maintains memoranda through sustained reverberatory neural activity (activity bumps) (Barbosa et al, 2020;Wimmer et al, 2014;Almeida et al, 2015;Qi et al, 2019;Nassar et al, 2018;Papadimitriou et al, 2015;Edin et al, 2009;Wei et al, 2012;Bouchacourt and Buschman, 2019;Compte et al, 2000). A feature of working memory that constrains the simultaneous storage of several items is the presence of swap errors (Schneegans and Bays, 2019).…”

Plasticity of Persistent Activity and Its Constraints

“…Neuromodulators have also been implicated in dynamic changes of persistent activity and are likely to be involved during learning or the selection of stimulus features. Most notably, cholinergic stimulation through the iontophoretic application of cholinergic agonists (Yang et al, 2013;Sun et al, 2017;Dasilva et al, 2019), or the stimulation of the cholinergic basal forebrain (Qi et al, 2019) leads to a general increase in activity of neurons in the prefrontal cortex. Conversely, systemic administration of the muscarinic antagonist scopolamine (Zhou et al, 2011) or iontophoresis of muscarinic and nicotinic-α7 inhibitors seems to depress prefrontal persistent activity (Yang et al, 2013;Major et al, 2015;Dasilva et al, 2019).…”