Modulation of Hippocampal Activity With Fornix Deep Brain Stimulation

Brain Stimul. Nov-Dec 2017;10(6):1125-1132. doi: 10.1016/j.brs.2017.09.002. Epub 2017 Sep 6.

Abstract

Background: Deep Brain Stimulation (DBS) within the Papez circuit is under investigation as a treatment for epilepsy and Alzheimer's disease. We previously reported the effects of stimulation at nodes within this network (anterior thalamic nucleus and hippocampus) on hippocampal activity in a large animal model, using a chronic implantable, clinical-grade system that permits concurrent stimulation and recording.

Objective: In this study we extended earlier work to compare the effects of fornix DBS on evoked potentials (EPs) and local field potential (LFP) activity within the hippocampus, and to assess closed-loop stimulation.

Methods: Unilateral fornix and hippocampal DBS leads were implanted in three ovine subjects using image-guided, frameless stereotaxy. Chronic, awake recordings of EPs and LFPs in response to fornix and hippocampal stimulation were collected with the implanted device and analyzed off-line.

Results: Stimulation of the fornix produced robust, short latency hippocampal EPs. High frequency fornix stimulation generated parameter-dependent effects. At low amplitudes, short lasting inhibition of LFP activity occurred. Above a specific amplitude threshold, DBS elicited pronounced bursts of theta activity, followed by a marked state shift in hippocampal activity. These effects persisted for minutes post-DBS and were reflected as changes in LFP spectral content and phase-amplitude coupling. Real-time modulation of hippocampal activity via the implanted device was demonstrated using LFPs as the control signal for closed-loop stimulation.

Conclusions: The current results expand earlier findings and demonstrate target-specific effects produced by DBS within this neural circuit. These changes in network activity may provide insights into stimulation targets and parameter selection for clinical investigations.

Keywords: Deep Brain Stimulation; Evoked potentials; Fornix; Hippocampus; Local field potentials.

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Anterior Thalamic Nuclei / diagnostic imaging
  • Anterior Thalamic Nuclei / physiology
  • Deep Brain Stimulation / methods*
  • Evoked Potentials / physiology
  • Female
  • Fornix, Brain / diagnostic imaging*
  • Fornix, Brain / physiology*
  • Hippocampus / diagnostic imaging
  • Hippocampus / physiology
  • Male
  • Sheep
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / physiology