Behavioral Investigations of Deep Brain Stimulation of the Basal Forebrain and its Application to Alzheimer’s Disease Treatment

抄録

Cognitive functions such as working memory and selective attention depend on the action of neuromodulators in the cerebral cortex, including acetylcholine.　Drugs that act on the cholinergic system improve cognitive function in human patients and animal models.　In a series of recent studies, we have demonstrated similar benefits with intermittent electrical stimulation of the basal forebrain.　We specifically targeted the Nucleus Basalis (NB) of Meynert, the source of acetylcholine in the cerebral cortex.　NB stimulation proved beneficial in a range of tasks involving working memory and attention.　NB stimulation may be particularly beneficial to human patients with Alzheimer’s disease, for whom these functions are compromised.　We examine the possible mechanisms of action of NB stimulation.　These include stimulation of cortical neurons, enhancement of synaptic connections, and regulation of blood flow.　 We present a hypothesis on how the amyloid formation in Alzheimer’s disease leads to cognitive decline, and how NB stimulation would impact this decline.　Our results offer promise for the application of deep brain stimulation as a therapy for Alzheimer’s disease.