Orientation selective DBS of entorhinal cortex and medial septal nucleus modulates activity of rat brain areas involved in memory and cognition

Abstract

The recently introduced orientation selective deep brain stimulation (OS-DBS) technique freely controls the direction of the electric field’s spatial gradient by using multiple contacts with independent current sources within a multielectrode array. The goal of OS-DBS is to align the electrical field along the axonal track of interest passing through the stimulation site. Here we utilized OS-DBS with a planar 3-channel electrode for stimulating the rat entorhinal cortex (EC) and medial septal nucleus (MSN), two promising areas for DBS treatment of Alzheimer’s disease. The brain responses to OS-DBS were monitored by whole brain functional magnetic resonance imaging (fMRI) at 9.4 T with Multi-Band Sweep Imaging with Fourier Transformation (MB-SWIFT). Varying the in-plane OS-DBS stimulation angle in the EC resulted in activity modulation of multiple downstream brain areas involved in memory and cognition. Contrary to that, no angle dependence of brain activations was observed when stimulating the MSN, consistent with predictions based on the electrode configuration and on the main axonal directions of the targets derived from diffusion MRI tractography and histology. We conclude that tuning the OS-DBS stimulation angle modulates the activation of brain areas relevant to Alzheimer’s disease, thus holding great promise in the DBS treatment of the disease.

Targeting papez circuit for cognitive dysfunction- insights into deep brain stimulation for Alzheimer's disease

“…The fornix, entorhinal cortex, and anterior thalamic nuclei were the promising targets for DBS in the memory circuits. Besides, the nucleus basalis of Meynert (NBM) and medial septal nuclei also serve as crucial targets of DBS in AD [ 54 ]. Animal models have produced great results in DBS of AD and other CNS pathologies.…”

“…While the DBS of the hippocampus has modulated the gene expression in the macaque model [ 139 ]. Recently Wu et al [ 54 ], utilised orientation-specific DBS (OS-DBS) with a planar 3-channel electrode for EC stimulation in rats, to advance the spatial selectivity of neuromodulation with DBS and the responses were monitored by fMRI studies. OS-DBS at 20 Hz significantly activated the perforant pathway of the hippocampus and also activated various downstream brain regions.…”