466 Deep Brain Stimulation of Nucleus Basalis of Meynert: Different Activation Patterns Results in Varying Spectral Topography in Cortex

INTRODUCTION: Deterioration of the basal nucleus of Meynert (NBM) is a key feature associated with dementia. The cholinergic projections of NBM serve as the primary source of Acetylcholine (ACh) for the entire neocortex. Research has demonstrated that NBM enhances cortical activity by influencing ACh release, which in turn affects neuro-excitability, spectral topography, and intra-cortical signaling in the neocortex. Moreover, NBM neurons have been observed to modulate their firing patterns during various cognitive processes. METHODS: (i) Various NBM stimulation parameters were tested in anesthetized adult rats. Default stimulation parameters were cathodic monopolar pulse with phasic patterns, 10 pulse/train with 100 ms train duration, train frequency of 100 Hz (inter-pulse frequency, IPF), and train repetition rate of 4 Hz (inter-burst frequency, IBF). (ii) In a separate experiment, the NBM-local field potential (LFP) and EEG from the auditory cortex (A1) were recorded from tethered normal, demented, and stimulated demented rats during audio tasks. RESULTS: (i) When different IBFs were tested, we saw a peak in the theta power at the 4–6 Hz range with the corresponding decrease in delta. The drastic reduction at 2 and 6 Hz indicates the circuitry's resonance sensitivity. Similarly, for different IPFs, the same pattern of a peak in theta and reduction in the delta was found at an IPF of 50–60 Hz. The pulse-width response was maximized at 6–8 ms. (ii) The different activation levels of NBM regulate the cross-frequency coupling strength of the NBM-cortical network. CONCLUSIONS: The present findings suggest that naturalistic NBM burst DBS may offer an effective therapy for treating dementia and suggest potential strategies for reevaluating current human NBM stimulation paradigms.