Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex

Lauri J Lehto, Pavel Filip, Hanne Laakso, Alejandra Sierra, Julia Slopsema, Matthew D Johnson, Lynn E. Eberly, Walter C Low, Olli Gröhn, Heikki Tanila, Silvia Mangia, Shalom Michaeli

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10 Scopus citations


Previous studies that focused on treating major depressive disorder with conventional deep brain stimulation (DBS) paradigms produced inconsistent results. In this proof-of-concept preclinical study in rats (n = 8), we used novel paradigms of orientation selective DBS for stimulating the complex circuitry crossing the infralimbic cortex, an area considered analogous to human subgenual cingulate cortex. Using functional MRI at 9.4 T, we monitored whole brain responses to varying the electrical field orientation of DBS within the infralimbic cortex. Substantial alterations of functional MRI responses in the amygdala, a major node connected to the infralimbic cortex implicated in the pathophysiology of depression, were observed. As expected, the activation cluster near the electrode was insensitive to the changes of the stimulation orientation. Hence, our findings substantiate the ability of orientation selective stimulation (OSS) to recruit neuronal pathways of distinct orientations relative to the position of the electrode, even in complex circuits such as those involved in major depressive disorder. We conclude that OSS is a promising approach for stimulating brain areas that inherently require individualisation of the treatment approach.

Original languageEnglish (US)
Article number899
JournalFrontiers in Neuroscience
StatePublished - Dec 13 2018

Bibliographical note

Funding Information:
The authors are grateful to Lynn Utecht for technical assistance with animal experiments and to Maple Shiao for processing of histological tissue sections. Funding. This work was supported by the National Institutes of Health U01-NS103569-01, the Center for Magnetic Resonance Research NIH core grant P41-EB015894, NIH R01-NS094206, NIH R01-NS094206, the EU H2020 Marie Sk?odowska RISE project #691110 (MICROBRADAM), Erkko foundation (OG), Academy of Finland (AS), and The Emil Aaltonen Foundation (LL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding bodies.

Publisher Copyright:
Copyright © 2018 Lehto, Filip, Laakso, Sierra, Slopsema, Johnson, Eberly, Low, Gröhn, Tanila, Mangia and Michaeli.


  • deep brain stimulation
  • depression
  • fMRI
  • infralimbic cortex
  • orientation selective


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