Response to Deep Brain Stimulation in Three Brain Targets with Implications in Mental Disorders: A PET Study in Rats.

Marta Casquero-Veiga,Manuel Desco,María Luisa Soto-Montenegro,Christine Winter,Javier Pascau,Ravit Hadar,Osama Ali Abulseoud

doi:10.1371/journal.pone.0168689

Abstract

ObjectiveTo investigate metabolic changes in brain networks by deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) and dorsomedial thalamus (DM) using positron emission tomography (PET) in naïve rats.Methods43 male Wistar rats underwent stereotactic surgery and concentric bipolar platinum-iridium electrodes were bilaterally implanted into one of the three brain sites. [18F]-fluoro-2-deoxy-glucose-PET (18FDG-PET) and computed tomography (CT) scans were performed at the 7th (without DBS) and 9th day (with DBS) after surgery. Stimulation period matched tracer uptake period. Images were acquired with a small-animal PET-CT scanner. Differences in glucose uptake between groups were assessed with Statistical Parametric Mapping.ResultsDBS induced site-specific metabolic changes, although a common increased metabolic activity in the piriform cortex was found for the three brain targets. mPFC-DBS increased metabolic activity in the striatum, temporal and amygdala, and reduced it in the cerebellum, brainstem (BS) and periaqueductal gray matter (PAG). NAcc-DBS increased metabolic activity in the subiculum and olfactory bulb, and decreased it in the BS, PAG, septum and hypothalamus. DM-DBS increased metabolic activity in the striatum, NAcc and thalamus and decreased it in the temporal and cingulate cortex.ConclusionsDBS induced significant changes in 18FDG uptake in brain regions associated with the basal ganglia-thalamo-cortical circuitry. Stimulation of mPFC, NAcc and DM induced different patterns of 18FDG uptake despite interacting with the same circuitries. This may have important implications to DBS research suggesting individualized target selection according to specific neural modulatory requirements.

Highlights

Mental disorders are the third leading cause of disability-adjusted life years (DALYs) loss and the first cause of years lived with disability (YLD) in Europe, accounting for 36.1% of those attributable to all causes[1]
deep brain stimulation (DBS) induced site-specific metabolic changes, a common increased metabolic activity in the piriform cortex was found for the three brain targets. medial prefrontal cortex (mPFC)-DBS increased metabolic activity in the striatum, temporal and amygdala, and reduced it in the cerebellum, brainstem (BS) and periaqueductal gray matter (PAG)
Across the neuro-psychiatric disorders currently subjected to DBS treatment trials, the following DBS targets are being tested: medial prefrontal cortex, globus pallidus internus, subthalamic nucleus, zona incerta, nucleus accumbens (NAcc)/ventral striatum, hippocampus and thalamus, lateral habenula, nucleus basali Meynert, medial forebrain bundle (MFB), and fornix/hypothalamus [21,22,23,24]

Summary

Introduction

Mental disorders are the third leading cause of disability-adjusted life years (DALYs) loss and the first cause of years lived with disability (YLD) in Europe, accounting for 36.1% of those attributable to all causes[1]. Deep brain stimulation (DBS) constitutes a neurosurgery technique that modifies neural activity by means of an electrical current applied directly to specific brain targets. It has been licensed as a treatment option for several movement disorders [3]. Across the neuro-psychiatric disorders currently subjected to DBS treatment trials, the following DBS targets are being tested: medial prefrontal cortex (mPFC), globus pallidus internus, subthalamic nucleus, zona incerta, nucleus accumbens (NAcc)/ventral striatum, hippocampus and thalamus (centromedian/parafascicularis; anterior nucleus; periaqueductal gray/periventricular gray; ventrolateral intermedius; ventral posterolateral/ventro-posteromedial), lateral habenula, nucleus basali Meynert, medial forebrain bundle (MFB), and fornix/hypothalamus [21,22,23,24]. From a theoretical point of view, the optimal DBS target would be the one that mostly interconnects with circuits involved in the manifestation of the symptoms to be targeted

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Conclusion