title: Hippocampal deep brain stimulation induces decreased rCBF in the hippocampal formation of the rat.
abstract: Deep brain stimulation (DBS) is a promising experimental approach to treat various neurological disorders. However, the optimal stimulation paradigm and the precise mechanism of action of DBS are unknown. Neuro-imaging by means of Single Photon Emission Computed Tomography (SPECT) is a non-invasive manner of evaluating regional cerebral blood flow (rCBF) changes, which are assumed to reflect changes in neural activity. In this study, rCBF changes induced by hippocampal DBS are evaluated by subtraction analysis of stimulation on/off using small animal microSPECT of the rat brain. Rats (n=13) were implanted with a multi-contact DBS electrode in the right hippocampus and injected with 10 mCi of HMPAO-Tc99(m) during application of various hippocampal DBS paradigms and amplitudes and during sham stimulation. Subtraction analysis revealed that hippocampal DBS caused a significant decrease in relative rCBF, both in the ipsi- (the side of the implanted electrode) and contralateral hippocampus. Hypoperfusion spread contralaterally with increasing stimulation amplitude. A clear distinction in spatial extent and intensity of hypoperfusion was observed between stimulation paradigms: bipolar Poisson Distributed Stimulation induced significant hypoperfusion ipsi- and contralaterally (p<0.01), while during other stimulation paradigms, rCBF-changes were less prominent. In conclusion, small animal microSPECT allows us to draw conclusions on the location, spatial extent and intensity of the hypoperfusion observed in the ipsi- and contralateral hippocampus, induced by hippocampal DBS. Our study demonstrates an innovative approach to visualize the effects of DBS and can be a useful tool in evaluating the effect of various stimulation paradigms and target areas for DBS.
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Ghent University Hospital, Ghent, Belgium. Tine.Wyckhuys@UGent.be
authors.forename: Tine
authors.initials: T
authors.lastname: Wyckhuys
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.forename: Bregt
authors.initials: B
authors.lastname: Van Nieuwenhuyse
authors.forename: Steven
authors.initials: S
authors.lastname: Deleye
authors.forename: Hans
authors.initials: H
authors.lastname: Hallez
authors.forename: Kristl
authors.initials: K
authors.lastname: Vonck
authors.forename: Robrecht
authors.initials: R
authors.lastname: Raedt
authors.forename: Wytse
authors.initials: W
authors.lastname: Wadman
authors.forename: Paul
authors.initials: P
authors.lastname: Boon
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods*; D007839:Functional Laterality; D006624:Hippocampus / Q000098:blood supply / Q000000981:diagnostic imaging / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D016012:Poisson Distribution; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D012815:Signal Processing, Computer-Assisted; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods