Cholinergic influence on visual cognitive processing

PROJECT SUMMARY/ABSTRACT Impairment in visual attention and working memory is common across mental illnesses and neurological conditions. Cholinergic drugs (acetylcholine agonists and acetylcholinesterase inhibitors) can ameliorate these symptoms, though their effectiveness is limited. An alternative way of improving cholinergic function is to stimulate the endogenous source of acetylcholine in the cerebral cortex, the Nucleus Basalis of Meynert. Recent results have shown the effectiveness of the approach in improving performance in working memory and attention tasks. However, the neuronal mechanisms of action in cortical areas involved in these processes are not yet understood. This project will investigate the effects of Nucleus Basalis stimulation on the activity of neurons in the dorsolateral prefrontal and posterior parietal cortex, as monkeys are performing visual working memory tasks. Neurophysiological recordings will be performed before, during, and after Nucleus Basalis stimulation. Our overarching hypothesis is that Nucleus Basalis stimulation broadens the tuning of prefrontal cortical neurons, which results in better stability of working memory representations, at the expense of accuracy for some conditions. We hypothesize that this effect generalizes to the posterior parietal cortex, as well. We will also determine the effects of stimulation on other aspects of neuronal firing and whether alternate mechanisms can account for behavioral effects of stimulation. Both acute effects of stimulation, in daily sessions, and sustained effects over a period of months, will be assessed. Systemic administration of cholinergic agents will also be performed and its effects on neural activity will be compared with those of Nucleus Basalis stimulation. The experiments will allow us to understand the effects of cholinergic transmission associated with performance of visual cognitive tasks. They will also evaluate the relative effectiveness of drug administration compared to deep brain stimulation. Our research will also provide a primate model for the evaluation of an intervention that can potentially improve cognitive function across a range of mental illnesses and neurological conditions.