Title Page
ABSTRACT
Contents
Chapter 1. Introduction 11
1.1. Research Background 11
Chapter 2. Parkinson's disease diagnosis and treatment 19
2.1. Material and Methods 19
2.1.1. Animals 19
2.1.2. 6 OHDA-induced parkinsonian rat 19
2.1.3. Gait test 20
2.1.4. Immunohistochemistry 20
2.1.5. Graphene electrode fabrication and stimulation 21
2.1.6. Treatment effect according to stimulation location (Electrotherapy) 21
2.1.7. Wireless device 22
2.1.8. Brainwave analysis 22
2.1.9. Brain slice preparation 23
2.1.10. Extracellular field recording 23
2.1.11. RNA sequencing 24
2.1.12. Differential expression analysis and data visualization 24
2.1.13. Statistics 24
2.2. Results 25
2.2.1. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats improves motor function 29
2.2.2. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats decreases high-frequency brain waves and increases low-frequency brain waves. 34
2.2.3. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats enhances mGluR-mediated, long-term synaptic plasticity. 37
2.2.4. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats alters gene expression in the glutamatergic synapse pathway. 41
2.3. Discussion 43
References 54
국문초록 59
Table 2.1. Specifications of NeuroStim (This work) and comparison with other wireless headstages. 46
Table 2.2. Statistical summary related to Fig 2.7D. Data are shown as means ± standard errors of the means. Independent sample t tests were used for the comparisons. 47
Table 2.3. Statistical summary related to Fig 2.7E-G. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way analysis of variance(ANOVA). 48
Table 2.4. Statistical summary related to Fig 2.9C. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way analysis of variance(ANOVA). 49
Table 2.5. Statistical summary related to Fig 2.11C. and Fig 2.11H. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way... 50
Table 2.6. Statistical summary related to Fig 2.11D and Fig 2.11I. Data are shown as means ± standard errors of the means. Statistical significance was determined using a one-way... 51
Table 2.7. Statistical summary related to Fig 2.7 52
Figure 2.1. Acute therapeutic STN stimulation reduces PAC in the resting state. Representative example of PAC observed in M1 of a Parkinson's disease patient before (left), during (middle)... 14
Figure 2.2. Risk factors for the development of Parkinson's disease. Results of epidemiological studies have revealed various environmental exposures that increase (OR＞1) or decrease (OR＜1)... 15
Figure 2.3. Flexible graphene electrode array and treatment of epilepsy. (a) Schematic of a graphene-based seizure sensor. (b) Optical images of a epilepsy treatment sensor on a tube. (c)... 16
Figure 2.4. Graphene-based microelectrode array for brain mapping on the cortical surface. (a) Schematic illustration of the graphene-based electrode array. (b) Optical image of the device on... 18
Figure 2.5. Wireless edge computing neuroprosthetic device implementation (A) Schematic showing wirelessly controlled microprocessor connection to 32 channel graphene electrode for... 26
Figure 2.6. Strategies for correcting the behavior and brain waves of freely living hemi-parkinsonian rats through wireless cortical recording and stimulation. (A) Graphene electrode... 28
Figure 2.7. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats improves motor function. (A) Overview of the timeline of the experiment. (B) A schematic showing the... 32
Figure 2.8. Cylinder test after apomorphine administration to assure a PD motor symptom. (A) Schematic illustrating contralateral rotation in 6-OHDA-intoxicated PD rats after apomorphine... 33
Figure 2.9. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats decreases high-frequency brain waves and increases low-frequency brain waves. (A) Representative... 35
Figure 2.10. Categorization of brainwave modification according to different parts (fore arm, hind arm and face) after applying 130 Hz cortical stimulation in PD rats. Data are presented as... 36
Figure 2.11. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats enhances mGluR-mediated, long-term synaptic plasticity. (A) Schematic illustration of electrode location... 40
Figure 2.12. High-frequency stimulation of the motor cortex of hemi-parkinsonian rats alters gene expression in the glutamatergic synapse pathway. (A) A heatmap illustrating the top 7... 42
Figure 2.13. Schematic illustration showing a circuit mechanism of how graphene stimulation implanted on the motor cortex can alleviate PD symptoms. The therapeutic effect of graphene... 45