早期盲人静息状态下局部脑活动研究
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摘要
目的早期盲作为单一模态的感觉缺失模型,基于任务的功能磁共振学已经做了大量的研究。近期有两篇静息态功能磁共振研究发现早期盲人视觉皮层与其它脑区之间功能连接发生改变,但是并不能确定是那个脑区改变引起的。低频振幅(Amplitude of low-frequence fluctuation, ALFF)和局部一致性(Regional homogeneity, ReHo)是由臧玉峰等提出的,它能够反映静息状态下脑自发性神经元活动,是研究静息状态下局部脑活动变化的指标。目前这两个指标已经用于生理状态及临床多种疾病的研究,且研究发现的异常与其疾病的病生理改变是一致的,这说明ALFF和ReHo能够反映病理状态下得脑活动改变。目前尚无研究早期盲人静息状态下局部脑活动改变的报道。本实验利用ALFF和ReHo研究早期盲人静息状态下局部脑活动的变化。
资料和方法本研究收集了16例早期盲人和32例性别、年龄相匹配的正常志愿者,利用3.0T磁共振仪器进行静息态及解剖像数据采集。采用SPM8 (http://www.fil.ion.ucl.ac.uk/spin)对数据进行预处理,预处理过程包括：时间校正、头动校正、空间标准化、重采样到3mm×3mm×3mm的立方体素、带通滤波(带宽：0.01-0.08Hz,以去掉高频噪声和低频漂移)和空间平滑(高斯核为6mm×6mm×6mm)。通过一定的算法计算出两组人的ALFF值(未标准化)和标准化的ALFF值,利用双样本t检验,得出两组之间存在差异的脑区。为了研究ALFF值与BOLD信号的关系,我们计算了早期盲人和正常对照组全脑及标准化状态下存在差异的5个脑区的活动幅度(activity amplitude, AM)值。利用REST软件(http://restfmri.net/forum/index.php)软件计算每个体素的ReHo值,通过逐个体素的分析得到每个人的ReHo图。为了消除个体差异的影响,我们计算出标准化的ReHo值,通过基于体素的分析,获得两组之间ReHo值存在显著差异的脑区。对两种指标均采用假阳性率(FDR)的多重比较校正方法(q<0.05,体素数>30)。
结果在严格控制被试头动、行为学表现及机械噪声等因素影响后,最终符合实验要求的早期盲人16例。与正常志愿者相比,早期盲人ALFF值(未标准化)呈显著性增高的脑区,主要位于双侧枕中回、忱下回、舌回、梭状回、距状沟皮质及颞下回;标准化ALFF值呈显著性增高的脑区与未标准化ALFF值呈显著性增高的脑区基本一致。与正常志愿者相比,标准化ReHo值呈显著性增高的脑区,主要包括：双侧枕下回、舌回、梭状回、距状沟皮质及濒下回、左侧枕中回。与正常志愿者相比,本研究未发现早期盲人ALFF及ReHo值呈显著性减低的脑区。这些结果与之前的PET研究发现静息状态下早期盲人视觉皮层脑血流量及糖代谢增高和脑皮层厚度增加是一致的。
结论第一,我们发现视觉皮层ALFF值增加与局部BOLD信号的均值及标准差增高是一致的,为证实ALFF能够反映静息状态下局部脑自发性活动提供了直接的证据；第二,早期盲人静息状态下视觉皮层局部脑活动增强,可能是在皮层发育阶段由于视觉缺失引起皮层-皮层连接、皮层-丘脑连接及皮层内部连接增多引起,这体现了经验依赖性可塑性变化。
Purpose Early blindness as a unimodal sensory deprivation model has been extensively studied by task-based functional magnetic resonance imaging. Recently two resting-state fMRI studies have reported altered functional connectivity between visual and other brain areas in early blind, however, they cannot answer which brain areas'local activities are changed. Amplitude of low-frequence fluctuation(ALFF) and Regional homogeneity (ReHo) are all proposed by Zang et al, which can reflect spontaneous neural activity, have become main indexes to study local brain activity in resting-state. So far, they have been used to investigate physical state and a variety of brain diseases, which are partly consistent with the pathophysiological changes in these disorders. There is no study on regional brain activity changes of early blind in resting-state. In our study, we use ALFF and ReHo to analyze changes of local brain activity in resting-state.
Materals and Methods All together sixteen early blind and thirty-two age- and gender-matched sighted subjects enrolled in our study. Resting-state fMRI scan and sagittal structural images were all collected using a 3.0-T scanner. All preprocessing steps were carried out using the statistical parametric mapping (SPM8, http://www.fil.ion.ucl.ac.uk/spm), including time slicing, reducing head movement, normalized to the MNI, resampling to to 3×3×3 mm cubic voxels, a band-pass frequency filter (0.01-0.08Hz, to reduce low-frequency drift and high-frequency noise), smoothed with a 6 mm full width at half maximum. The unnormalized and normalized ALFF and ReHo values were calculated using specific algorithms, brain areas with significant changes in ALFF or ReHo values between groups were acquired by a two-sample t test. To study the relationship of between ALFF and the underlying blood oxygen level-dependent (BOLD) signals, we measured the activity amplitude (AM) of the whole brain and five regions of interest (ROI) with significantly increased ALFF values in the early blind under a normalized method. After we got the ReHo value of every voxel, an individual ReHo map was obtained on a voxel by voxel basis using REST software. To reduce the effect of individual variance, we normalized the Reho value of each voxel by dividing the mean Reho of the whole brain for each subject. Brain areas with significant changes in ReHo values between the two groups were acquired by voxel-based analysis. Multiple comparisons were statistically corrected by false discovery rate (FDR) with thresholds of q<0.05 and cluster size>30 voxels.
Results Sixteen blind subjects were recruited in the final statistics. Compared to sighted subjects, the early blind showed significantly increased ALFF (unnormalized) in visual areas including the bilateral middle and inferior occipital gyri, lingual and fusiform gyri, calcarine cortices and inferior temporal gyri; the significantly increased ALFF was present in the similar brain areas in normalized analysis as in the unnormalized analysis; the early blind showed increased ReHo in visual areas including the bilateral inferior occipital gyri, lingual and fusiform gyri, calcarine cortices, and inferior temporal gyri, left middle occipital gyri. However, we did not find significantly decreased ALFF and ReHo in any brain area in the early blind comparing to that in the sighted controls. These findings are consistent with prior positron emission tomography studies which showed increased resting-state cerebral blood flow and glucose metabolism in the visual areas of early blind and thicker visual cortex.
Concusion Firstly, we found increased ALFF in visual areas in early blind corresponding to the increased mean and standard deviation of regional BOLD signals, which provides direct evidence to the hypothesis that ALFF reflects the level of the resting-state brain activity. Secondly, we suggest that high resting-state brain activity in the visual areas of the early blind could be partially ascribed to the increased corticocortical, thalamocortical and intracortical connections due to lack of visual experience during critical cortex developmental period.
资料和方法本研究收集了16例早期盲人和32例性别、年龄相匹配的正常志愿者,利用3.0T磁共振仪器进行静息态及解剖像数据采集。采用SPM8 (http://www.fil.ion.ucl.ac.uk/spin)对数据进行预处理,预处理过程包括：时间校正、头动校正、空间标准化、重采样到3mm×3mm×3mm的立方体素、带通滤波(带宽：0.01-0.08Hz,以去掉高频噪声和低频漂移)和空间平滑(高斯核为6mm×6mm×6mm)。通过一定的算法计算出两组人的ALFF值(未标准化)和标准化的ALFF值,利用双样本t检验,得出两组之间存在差异的脑区。为了研究ALFF值与BOLD信号的关系,我们计算了早期盲人和正常对照组全脑及标准化状态下存在差异的5个脑区的活动幅度(activity amplitude, AM)值。利用REST软件(http://restfmri.net/forum/index.php)软件计算每个体素的ReHo值,通过逐个体素的分析得到每个人的ReHo图。为了消除个体差异的影响,我们计算出标准化的ReHo值,通过基于体素的分析,获得两组之间ReHo值存在显著差异的脑区。对两种指标均采用假阳性率(FDR)的多重比较校正方法(q<0.05,体素数>30)。
结果在严格控制被试头动、行为学表现及机械噪声等因素影响后,最终符合实验要求的早期盲人16例。与正常志愿者相比,早期盲人ALFF值(未标准化)呈显著性增高的脑区,主要位于双侧枕中回、忱下回、舌回、梭状回、距状沟皮质及颞下回;标准化ALFF值呈显著性增高的脑区与未标准化ALFF值呈显著性增高的脑区基本一致。与正常志愿者相比,标准化ReHo值呈显著性增高的脑区,主要包括：双侧枕下回、舌回、梭状回、距状沟皮质及濒下回、左侧枕中回。与正常志愿者相比,本研究未发现早期盲人ALFF及ReHo值呈显著性减低的脑区。这些结果与之前的PET研究发现静息状态下早期盲人视觉皮层脑血流量及糖代谢增高和脑皮层厚度增加是一致的。
结论第一,我们发现视觉皮层ALFF值增加与局部BOLD信号的均值及标准差增高是一致的,为证实ALFF能够反映静息状态下局部脑自发性活动提供了直接的证据；第二,早期盲人静息状态下视觉皮层局部脑活动增强,可能是在皮层发育阶段由于视觉缺失引起皮层-皮层连接、皮层-丘脑连接及皮层内部连接增多引起,这体现了经验依赖性可塑性变化。
Purpose Early blindness as a unimodal sensory deprivation model has been extensively studied by task-based functional magnetic resonance imaging. Recently two resting-state fMRI studies have reported altered functional connectivity between visual and other brain areas in early blind, however, they cannot answer which brain areas'local activities are changed. Amplitude of low-frequence fluctuation(ALFF) and Regional homogeneity (ReHo) are all proposed by Zang et al, which can reflect spontaneous neural activity, have become main indexes to study local brain activity in resting-state. So far, they have been used to investigate physical state and a variety of brain diseases, which are partly consistent with the pathophysiological changes in these disorders. There is no study on regional brain activity changes of early blind in resting-state. In our study, we use ALFF and ReHo to analyze changes of local brain activity in resting-state.
Materals and Methods All together sixteen early blind and thirty-two age- and gender-matched sighted subjects enrolled in our study. Resting-state fMRI scan and sagittal structural images were all collected using a 3.0-T scanner. All preprocessing steps were carried out using the statistical parametric mapping (SPM8, http://www.fil.ion.ucl.ac.uk/spm), including time slicing, reducing head movement, normalized to the MNI, resampling to to 3×3×3 mm cubic voxels, a band-pass frequency filter (0.01-0.08Hz, to reduce low-frequency drift and high-frequency noise), smoothed with a 6 mm full width at half maximum. The unnormalized and normalized ALFF and ReHo values were calculated using specific algorithms, brain areas with significant changes in ALFF or ReHo values between groups were acquired by a two-sample t test. To study the relationship of between ALFF and the underlying blood oxygen level-dependent (BOLD) signals, we measured the activity amplitude (AM) of the whole brain and five regions of interest (ROI) with significantly increased ALFF values in the early blind under a normalized method. After we got the ReHo value of every voxel, an individual ReHo map was obtained on a voxel by voxel basis using REST software. To reduce the effect of individual variance, we normalized the Reho value of each voxel by dividing the mean Reho of the whole brain for each subject. Brain areas with significant changes in ReHo values between the two groups were acquired by voxel-based analysis. Multiple comparisons were statistically corrected by false discovery rate (FDR) with thresholds of q<0.05 and cluster size>30 voxels.
Results Sixteen blind subjects were recruited in the final statistics. Compared to sighted subjects, the early blind showed significantly increased ALFF (unnormalized) in visual areas including the bilateral middle and inferior occipital gyri, lingual and fusiform gyri, calcarine cortices and inferior temporal gyri; the significantly increased ALFF was present in the similar brain areas in normalized analysis as in the unnormalized analysis; the early blind showed increased ReHo in visual areas including the bilateral inferior occipital gyri, lingual and fusiform gyri, calcarine cortices, and inferior temporal gyri, left middle occipital gyri. However, we did not find significantly decreased ALFF and ReHo in any brain area in the early blind comparing to that in the sighted controls. These findings are consistent with prior positron emission tomography studies which showed increased resting-state cerebral blood flow and glucose metabolism in the visual areas of early blind and thicker visual cortex.
Concusion Firstly, we found increased ALFF in visual areas in early blind corresponding to the increased mean and standard deviation of regional BOLD signals, which provides direct evidence to the hypothesis that ALFF reflects the level of the resting-state brain activity. Secondly, we suggest that high resting-state brain activity in the visual areas of the early blind could be partially ascribed to the increased corticocortical, thalamocortical and intracortical connections due to lack of visual experience during critical cortex developmental period.
引文
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