Deep brain stimulation of nucleus basalis of meynert: Effect of stimulation mode and duration on learning in rat model of dementia.

Abstract

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been preliminarily investigated as a potential treatment for dementia. The degeneration of NBM cholinergic neurons is a pathological feature of many forms of dementia. Although NBM stimulation has been demonstrated to improve learning, the ideal parameters for NBM stimulation have not been elucidated. This study assesses the differential effects of varying stimulation patterns and duration on learning in a dementia rat model with cholinergic deficits. 192-IgG saporin (SAP) or Dulbecco's phosphate buffered saline was injected into the NBM to produce dementia in rats. Next, all rats underwent unilateral implantation of a DBS electrode in the NBM. The experimental groups consisted of (a) normal, (b) untreated SAP-injected rats with cholinergic deficits, and (c) SAP rats receiving NBM DBS. The stimulation paradigms included testing different modes (tonic and burst) and durations (1 hr, 5 hr, and 24 hr/day) over 10 daily sessions. Memory was assessed using two established learning paradigms: novel object recognition and auditory operant chamber learning. Both normal and stimulated rats demonstrated improved performance in novel object recognition and auditory learning as compared to the unstimulated SAP group. The burst stimulation groups performed better than the tonic group. Increasing the daily stimulation duration to 24 hr did not further improve cognitive performance in an auditory recognition task and degraded the results on a novel object recognition task as compared with 5 hr. The present findings suggest that naturalistic NBM burst DBS may offer potential effective therapy for treating dementia and suggests potential strategies for the reevaluation of current human NBM stimulation paradigms. (PsycInfo Database Record (c) 2025 APA, all rights reserved).