Modulation of Theta-Band Local Field Potential Oscillations Across Brain Networks With Central Thalamic Deep Brain Stimulation to Enhance Spatial Working Memory.

Ching-Wen Chang,Ssu-Ju Li,Yun-Chi Chang,Yueh-Jung Chung,Vina Ro,Christine Chin-Jung Hsieh,Shin-Yuan Chen,Shih-Hung Yang,Chao-Hung Kuo,Chi-Wei Lee,You-Yin Chen,Sheng-Huang Lin,Ting-Chun Lin,Hui-Ching Lin,Yu-Chun Lo

doi:10.3389/fnins.2019.01269

Abstract

Deep brain stimulation (DBS) is a well-established technique for the treatment of movement and psychiatric disorders through the modulation of neural oscillatory activity and synaptic plasticity. The central thalamus (CT) has been indicated as a potential target for stimulation to enhance memory. However, the mechanisms underlying local field potential (LFP) oscillations and memory enhancement by CT-DBS remain unknown. In this study, we used CT-DBS to investigate the mechanisms underlying the changes in oscillatory communication between the CT and hippocampus, both of which are involved in spatial working memory. Local field potentials (LFPs) were recorded from microelectrode array implanted in the CT, dentate gyrus, cornu ammonis (CA) region 1, and CA region 3. Functional connectivity (FC) strength was assessed by LFP–LFP coherence calculations for these brain regions. In addition, a T-maze behavioral task using a rat model was performed to assess the performance of spatial working memory. In DBS group, our results revealed that theta oscillations significantly increased in the CT and hippocampus compared with that in sham controls. As indicated by coherence, the FC between the CT and hippocampus significantly increased in the theta band after CT-DBS. Moreover, Western blotting showed that the protein expressions of the dopamine D1 and α4-nicotinic acetylcholine receptors were enhanced, whereas that of the dopamine D2 receptor decreased in the DBS group. In conclusion, the use of CT-DBS resulted in elevated theta oscillations, increased FC between the CT and hippocampus, and altered synaptic plasticity in the hippocampus, suggesting that CT-DBS is an effective approach for improving spatial working memory.

Highlights

Deep brain stimulation (DBS) is a well-established neurosurgical technique applied during treatment for movement and psychiatric disorders
In the T-maze behavioral task, the rats were required to explore the routes for the water reward, and the behavioral performance indicators, i.e., latency time and spatial working memory index (SWMI), were analyzed to compare the central thalamus (CT)-DBS effects on behavioral performance between the two groups
local field potential (LFP) were recorded in the CT, CA1, CA region 3 (CA3), and dentate gyrus (DG)

Summary

Introduction

Deep brain stimulation (DBS) is a well-established neurosurgical technique applied during treatment for movement and psychiatric disorders. DBS has been used to treat a variety of neurological disorders by targeting nuclei in different brain regions. Patients with Parkinson’s disease (PD) demonstrated improved motor symptoms after the application of DBS in the subthalamic nucleus, which is a key node in the functional control of motor activity in basal ganglia (Benabid, 2003; Duncan et al, 2018). After DBS in the nucleus accumbens (NAc) in patients with autism spectrum disorders, the patients’ social communication skills were enhanced, and decreased metabolism in the prefrontal and frontal cortex were observed through fluorodeoxyglucose-positron emission tomography (Park et al, 2016). Patients with major depressive disorder (MDD) treated with DBS in medial forebrain bundle had exhibited an improvement in their depression score due to the DBS-induced modulation of the mesolimblic reward system (Temel et al, 2015)

Methods

Results

Conclusion