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.

A 1 Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland

Center for Magnetic Resonance Research University of Minnesota Minneapolis MN USA

Department of Neurology 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic

Department of Neurosurgery University of Minnesota Minneapolis USA

Division of Biostatistics School of Public Health University of Minnesota Minneapolis MN USA

Radiology Department Center for MR Research University of Minnesota 2021 6th St SE Minneapolis MN 55455 USA

University of Campania Luigi Vanvitelli Naples Italy

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