手运动技能转移后的大脑激活模式

doi:10.3969/j.issn.1673-5374.2013.07.008

摘要/Abstract

摘要：

运动训练的交叉迁移是与运动学习相关的现象。通过这种现象，一侧肢体进行运动训练使对侧未训练肢体运动能力得到明显提高。实验旨在探讨一侧肢体执行序列反应时任务时，对侧未训练的肢体运动功能是否得到提高，这些能力的获得是否使大脑激活模式发生改变。我们招募20名右利手的健康被试，随机分为训练和未训练的对照组。训练组给予左手进行2周的序列反应时任务训练，而对照组则不进行训练。训练前后检测执行序列反应时任务时反应时和准确率，同时在未训练的右手在执行序列反应时任务时进行脑部功能MRI扫描。训练后右手和左手的反应时和准确率均发生明显改变，对照组未训练的右手则无明显变化。训练组未训练的右手执行序列反应时任务时，与运动功能相关的大脑皮质激活体积减小，但小脑蚓和小脑齿状核激活明显增强，并伴随交叉运动学习效应。对照组脑激活模式则未发生明显改变。提示2周的运动能力学习使训练手的运动能力转移至对侧未训练手，未训练手的运动能力的获得使大脑皮质和小脑激活模式发生改变。

关键词: 神经再生, 神经影像, 运动训练, 交叉训练效应, 运动技能学习, 皮质激活, 小脑激活, 序列反应时任务, 功能MRI, 反应时, 反应准确率, 初级运动皮质, 齿状核, 小脑蚓, 基金资助文章, 图片

Abstract:

Cross-training is a phenomenon related to motor learning, where motor performance of the untrained limb shows improvement in strength and skill execution following unilateral training of the homologous contralateral limb. We used functional MRI to investigate whether motor performance of the untrained limb could be improved using a serial reaction time task according to motor sequential learning of the trained limb, and whether these skill acquisitions led to changes in brain activation patterns. We recruited 20 right-handed healthy subjects, who were randomly allocated into training and control groups. The training group was trained in performance of a serial reaction time task using their non-dominant left hand, 40 minutes per day, for 10 days, over a period of 2 weeks. The control group did not receive training. Measurements of response time and percentile of response accuracy were performed twice during pre- and post-training, while brain functional MRI was scanned during performance of the serial reaction time task using the untrained right hand. In the training group, prominent changes in response time and percentile of response accuracy were observed in both the untrained right hand and the trained left hand between pre- and post-training. The control group showed no significant changes in the untrained hand between pre- and post-training. In the training group, the activated volume of the cortical areas related to motor function (i.e., primary motor cortex, premotor area, posterior parietal cortex) showed a gradual decrease, and enhanced cerebellar activation of the vermis and the newly activated ipsilateral dentate nucleus were observed during performance of the serial reaction time task using the untrained right hand, accompanied by the cross-motor learning effect. However, no significant changes were observed in the control group. Our findings indicate that motor skills learned over the 2-week training using the trained limb were transferred to the opposite homologous limb, and motor skill acquisition of the untrained limb led to changes in brain activation patterns in the cerebral cortex and cerebellum.

Key words: neural regeneration, neuroimaging, cross-training effects, motor skill learning, cortical activation, cerebellar activation, serial reaction time task, functional MRI, response time, response accuracy, primary motor cortex, dentate nucleus, vermis, grants-supported paper, photographs-containing paper, neuroregeneration

. 手运动技能转移后的大脑激活模式[J]. 中国神经再生研究(英文版), 2013, 8(7): 639-646.

Yong Hyun Kwon, Jung Won Kwon, Ji Won Park. Changes in brain activation patterns according to cross-training effect in serial reaction time task An functional MRI study[J]. Neural Regeneration Research, 2013, 8(7): 639-646.

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引言

材料方法

Design
A comparative functional MRI experiment with repeated measurements.

Time and setting
This study was performed at functional MRI room, Medical Center, Yeungnam University, Republic of Korea, from June to August 2012.

Subjects
Twenty healthy volunteers participated in this study by recruitment notice using the following inclusive criteria: (1) right-handed as confirmed by the modified Edinburg Handedness Inventory^[33]; (2) no previous history of neurological or psychiatric illness; (3) no previous participation in experiments regarding motor sequencing learning with serial reaction time tasks. All subjects were randomly divided into training (6 males, mean age: 24.7 ± 2.4 years) or control groups (6 males, mean age: 24.9 ± 2.6 years). To control the known effects of the serial reaction time task, age and sex were matched in the two groups (P > 0.05). The subjects understood the purpose of this study and provided written informed consent prior to participation of this study, in accordance with the ethical standards of the Declaration of Helsinki ^[34].

Methods
Motor task paradigm and training procedure
Subjects were seated in a comfortable chair and placed 50 cm in front of a 17-inch monitor. The square-shaped response buttons were arranged horizontally on a response box connected to a computer. The motor task paradigm was designed using SuperLab Pro 4.0 software (Cedrus Co., San Pedro, CA, USA). Each button was labeled with a number representing the finger of the left hand to be used (1, 2, 3, and 4 represented the index, middle, ring, and little fingers, respectively). Motor sequence was composed of a combination of 1, 2, 3, and 4, which were randomly presented on the center of the computer monitor, with equal probabilities of 20%. A total of 200 stimuli per session were provided, and there were 50 trials for each number. When one of the numbers was presented on the screen, the subject was instructed to press the corresponding response button as accurately and quickly as possible using the dominant (right) hand. Stimuli were presented for a period of 1 000 ms, and the interval time between each stimulus was 500 ms for preparation of the next stimuli. Finally, one training session lasting 8 minutes consisted a 5-minute run phase and a 3-minute resting phase. The non-dominant left hand in the training group performed five repetitions of each training session for 40 minutes per day. The training group received 5 days of motor training per week for 2 consecutive weeks, whereas the control group did not receive any training. Figure 2 indicates the motor task and the functional MRI paradigm in the total experimental procedure.

Behavioral and functional MRI measurements during the pre- and post-training
Functional MRI scanning was performed on all participants in a supine position. The head, trunk, and arms were restrained to prevent motion artifacts during functional MRI experiments. The serial reaction time task for functional MRI scanning was presented by SuperLab Pro 4.0 software. Through a tilted mirror on the head coil of the MRI equipment, a rear-projection screen outside of the scanner was visible to the participants. According to the visual stimulation presented on the screen, participants pressed the buttons (LU440-LINE, Cedrus Co.), which were arranged horizontally on a response box connected to a computer. For the functional MRI paradigm, the activation paradigm was designed as four repeating blocks, which consisted of the serial reaction time task phase and the resting phase (each for 63 seconds). A ready period of 3 seconds was provided to allow the participants to prepare for task performance. Finally, to test region-specific condition effects for each of the phases, we subtracted the four resting phases from the four serial reaction time task phases.

To measure the changes in motor response and cortical activation pattern according to the cross-training effect, functional MRI scanning was performed twice during pre- and post-training, while the subjects performed the serial reaction time task with their dominant right hand using the same paradigm of the training procedure. The examiner continuously monitored the situation of the task performance through a video camera outside of the functional MRI scanner. Before performance of the serial reaction time task, all subjects took a practice block for accommodation with the task and the experimental procedure. In the behavioral function of the reaction time at the two tests, response time and percentile of correct response were measured using SuperLab Pro 4.0 software.

Functional MRI analysis
The blood oxygenation level-dependent functional MRI measurement, which employs the echo planar imaging technique, was performed using a 1.5-T Philips Gyroscan Intera scanner (Hoffman-LaRoche, Ltd., Best, The Netherlands) with a standard head coil. Foam padding was used to secure and limit the head motion of each participant within the coil. Twenty-eight slices were acquired using a single shot echo planar imaging sequence (time of repetition/echo time = 3 000/50 ms, flip angle 70?, field of view 210 mm, matrix 64 × 64, slice thickness 5 mm), and each functional run consisted of 85 images (including 5 dummies). Repetitive alternating phases of control and stimulation with serial reaction time task were performed as the stimulation task. Each “control and stimulation” task was repeated four times.

SPM8 software (Wellcome Department of Cognitive Neurology, London, UK) was used for analysis of all functional images. A slice timing correction and motion realignment were used for preprocessing of all images. Next, for multiple-subject comparisons, we performed spatial normalization to the Montreal Neurological Institute echo planar imaging template supplied with SPM8 software, and smoothing with an 8 mm the full width at half maximum Gaussian kernel. Differences in brain activation between the training and control groups were compared by a random effect group analysis (corrected P < 0.001). Quantitative comparisons between the training and control groups were obtained in terms of the changes of blood oxygenation level-dependent signal in selected regions of interest, focusing on the hand area of the primary sensorimotor area, premotor area, supplementary motor area, posterior parietal lobes, and cerebellum. For blood oxygenation level-dependent signal analysis, spherical volumes of interest (5 mm radius) were defined using the Talairach coordinates of the highest t values in the regions of interest of individual data. Averaged map changes of blood oxygenation level-dependent signal intensities by group analysis were extracted for each volume of interest using the differences of signal changes between the activation and recall conditions of each functional MRI experiment.

Statistical analysis
An independent t-test was used for the comparison of differences between the training and control groups in terms of the baseline data for response time, percentile of correct response, and age. All data were evaluated through separate univariate analyses of variance, using two-way repeated measures analysis of variance (groups: training group, control group) × 2 (test sessions: pre-training, post-training) on the two dependent variables of response time and correct response. PASW 18.0 (SPSS, Chicago, IL, USA) was used for all statistical analyses. P < 0.05 was considered statistically significant.

Funding: This study was supported by the Yeungnam College of Science & Technology Research Grants in 2012.
Author contributions: Yong Hyun Kwon and Ji Won Park designed this study and wrote the paper. Jung Won Kwon acquired and analyzed experimental data. All authors approved the final version of the paper.
Conflicts of interest: None declared.
Ethical approval: The study protocol was approved by the Ethics Committee, Institutional Review Board of Yeungnam University Hospital, Republic of Korea.
Author statements: The manuscript is original, has not been submitted to or is not under consideration by another publication, has not been previously published in any language or any form, including electronic, and contains no disclosure of confidential information or authorship/patent application/funding source disputations.