MicroPET Imaging of Thalamic and Cortical Activation in Rat Brain Responding to Different Modalities of Stimulation and Development of Multichannel Electrodes for Neuronal Signals Recording
Date Issued
2004
Date
2004
Author(s)
Chen, You-Yin
DOI
en-US
Abstract
Adequately understanding the brain function is one of the outstanding challenges in neuroscience. The brain is an unresting assembly of cells that continually process spatial distributed information, analyzes it, perceives it, and makes decision. Therefore, the goal of functional brain mapping is to isolate local neuronal activity associated with sensory, motor, and cognitive function or with emotional process.
This study aims to clarify the process mechanism of the brain in the spatial and temporal domains under a given task or behavior. Functional imaging and electrophysiology techniques are powerful tools to investigate the anatomical and functional information on neuronal activity within the brain. A functional imaging needs both millimeter precision in localizing regions of activated tissue and subsecond temporal precision for characterizing changes in patterns of activation over time. Electrophysiological methods can provide the temporal resolution as fine as the analog-to-digital sampling rate (typically in the 1 – to 10-msec range), and its exquisite sensitivity to changes neuronal activity has been recognized.
This study used the rat tail as a simple model of the sensory system. It is chosen for two simple reasons: first, the previous work has found that the receptive field of rat tail is very small (1 mm3), therefore, it is good to save manpower to study it in detail; second, the tail is sufficiently long to easily attach an electrical stimulator or other natural modalities of stimulation. To acquire the functional image of the rat brain, positron emission tomography (PET) with high resolution and sensitivity was adopted to assess the metabolic activity. Using [18F]fluorodeoxyglucose (FDG) as the radiotracer, we demonstrate the high-resolution PET scanner (microPET) has sufficient resolution to image metabolic function of the rat brain as well as to determine patterns of neuronal activation produced by different modalities of stimulation. In this study microPET was used to investigate neuronal activation of thalamic and cerebral cortical responses to electrical stimuli (ES), mechanical stimuli (MS), different intensities of temperature stimuli and noxious stimuli (cold and heat) of the left side of the rat tail. We first evaluated sodium pentobarbital and ketamine to determine their effect on microPET images. Pentobarbital anesthesia significantly reduced FDG uptake in neural tissues, blurring images; therefore, ketamine was use to anesthetize animals during microPET. After rats were anesthetized and secured in a laboratory-made stereotaxic frame, a simple, noninvasive stereotaxic technique was used to position their heads in the microPET scanner and to precisely confirm the images in the stereotaxic atlas. An activation index (AI) represented changes in metabolic activity in neural tissues. ES resulted in more increases in FDG uptake in the contralateral thalamus (AI = 18) and cortex (AI = 12.5), with significant side-to-side differences (P < .05, paired t-test). MS induced more uptakes in contralateral cortex (AI = 9.5), with the significant side-to-side differences (P < .05, paired t-test). However, lateralized differences were absent in the thalamus (P > .05, paired t-test) due to the limited spatial resolution of microPET. In the warm-discrimination study, two intensities of innocuous heat (35℃ and 40℃) were applied to the left side of the rat tail for 30 minutes. Significant increases in FDG uptakes to both 35℃ and 40℃ stimuli were found in the contralateral thalamus and cortex. The results FDG uptakes in contralateral thalamus were also showed the significant discrimination between 40℃ (AI = 17.34) stimulus and 35℃ stimuli (AI = 12.56; P < .05, paired t-test). The innocuous cold (15℃) showed significant side-to-side differences (P < .05, paired t-test) between bilateral thalamus and cortex. The results showed two forms of noxious stimuli (> 45℃ and < 6℃) increase FDG uptakes in bilateral thalamus and cortex but no significant bilateral difference occurs.
To compensate for the insufficiency in the temporal resolution of microPET, this study used the electrophysiological technology to record the firing patterns of neurons one at a time while stimuli were presented. In this study, to record from many neurons simultaneously, a multichannel electrode has been fabricated to record the thalamic field potentials (FPs) responding to the electrical stimulation of nerve at the rat tail. At first, the number of sweeps used to form the evoked FP average and the spatial sampling density were determined by using cross-correlation functions, which were then statistically analyzed. The difference was significant at P < 0.05, if the number of sweeps for averaging was more than 50 and the spatial interval between two consecutive recording sites was less than 50 μm in the anteroposterior, mediolateral and ventrodorsal directions. The responsive area was distributed vertically in the thalamus (ventral posterior lateral [VPL] nucleus); therefore, the recording sites were arranged in one linear array. Sixteen recording sites, which were 50 μm apart from each other, were distributed in the ventrodorsal direction. A 16-channel silicon probe was fabricated by using a standard photolithography process and laser micromachining techniques. The probe provides capabilities to record multiple field potentials and multiunit activities simultaneously.
The multichannel electrode has been developed and high-resolution PET scanner is now available. Combination of imaging with electrophysiological techniques will enhance understanding of mental activities directly, follow their progress in the living brain, and make inferences regarding higher cortical functions. The area will be the wave of the future.
Subjects
交互相關係數；多通道微電極探針
場電位
正子斷層
氟-18去氧 葡萄糖
微正子斷層照影
雷射微加工技術
微機電製程
Field potential
Micro-electro-machining
Laser micromachining
Positron emission tomography
FDG
MicroPET
Multielectrode probe
Cross-correlation
Type
thesis
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