小脑参与痛觉调节的fMRI研究

目的利用功能磁共振成像技术(f MRI)观察小脑各亚区在不同强度电刺激时的激活反应,探讨小脑对于痛觉调控的作用。方法对10名右利手健康志愿者分别施加1倍痛阈、3倍痛阈两个不同强度的电刺激任务,同期进行全脑f MRI扫描,应用功能性神经图像分析(AFNI)软件包进行后处理以显示小脑激活的变化。结果非伤害性电刺激(1倍痛阈强度)主要激活对侧小脑半球小叶Ⅵ、Ⅶ区和同侧小脑半球Ⅶ、Ⅷ区,以同侧半球的BOLD信号较强;伤害性电刺激(3倍痛阈强度)诱发的激活区主要位于同侧小脑半球小叶Ⅲ~Ⅵ区,对侧小脑半球Ⅵ区,前蚓部,蚓旁区和深部小脑核团的一部分(顶核和齿状核),其中仍以同侧激活区范围较大,信号亦明显强于对侧。结论高强度痛觉电刺激额外激活同侧小脑半球小叶Ⅲ~Ⅵ区,前蚓部,蚓旁区和深部小脑核团,这些脑区应该属于小脑伤害感受性环路的一部分,它们可能在全身痛觉调控网络中更为重要。     

人脑视觉皮质功能磁共振成像研究

目的研究人脑视觉皮质血氧水平依赖（BOLD）的功能磁共振成像。方法18名正常健康志愿者，在光刺激和非刺激的两种对比条件下，采用EP1技术，采集视觉皮质血氧水平依赖（BOLD）图像。t检验分析得出光刺激状态和非刺激状态信号对比的脑功能图像。结果fMRI图像显示光刺激下脑功能活动激活区主要位于双侧视觉皮质区。结论fMRI可用于在活体人脑上研究各功能区活动，光刺激下的fMRI可对人脑视觉皮质进行定位。     

正常人简体汉字词组短时记忆刺激的脑fMRI实验研究

目的 本实验是运用功能磁共振成像（fMRI)研究志愿者简体汉字词组短时记忆刺激的脑内活动区情况：方法 10例正常志愿者作为研究对象。运用单次激发GRE-EPI分别在横断位、冠状位和矢状位扫描采集fMRI图像，以简体汉字词组短时记忆为刺激：fMRI图像和T1W解剖图像在三个断面融合，并进行脑内活动区出现率分析：结果 横断位图像上出现24个活动区．冠状位图像上出现20个活动区，矢状位图像上出现24个活动区：结论 本实验的fMRI研究显示正常人简体汉字单词短时记忆刺激的脑内活动区主要位于PFC，颞叶一海马、枕叶和小脑等。     

健康人双任务范式汉字加工的功能磁共振成像研究

目的利用功能磁共振成像(fMRI)考察健康人双任务范式下汉字加工过程。方法10 名健康受试者分别进行双任务范式的“ 按键朗读” 任务及单任务范式的“ 按键”“ 朗读” 任务。采用标准的组块相关设计对受试者大脑进行fMRI扫描,观察任务中脑功能激活区及偏侧化指数。结果和结论执行任务时,右侧额下回、双侧顶叶、双侧小脑显著激活;偏侧化指数显示,脑激活区呈现左半球优势。     

右侧正中神经电刺激促醒疗法对健康人脑功能影响的fMRI研究

目的 探讨右侧正中神经电刺激（RMNS）促醒疗法对健康人脑功能的影响。 方法 选取28例健康志愿者作为受试者，将RMNS促醒治疗模式作为任务刺激，采用Block实验设计，给予受试者30 s刺激-30 s休息共重复6次，并同步采用大脑功能磁共振成像(fMRI)技术进行成像扫描。使用SPM 12软件进行统计处理时将同一受试者刺激状态与静息状态的脑功能成像互为对照，分析其脑区激活情况。 结果 fMRI检查显示，RMNS促醒治疗模式下健康人脑正激活区主要集中在左侧初级运动皮质(M1)、皮质运动前区(PMC)，双侧初级体感皮质(S1）、双侧次级体感皮质(S2)及左侧岛叶。与静息态相比，RMNS促醒刺激模式下上述激活脑区BOLD信号强度变化较大，T>5.84，P<0.05（FWE校正）。 结论 右侧正中神经电刺激促醒治疗能通过激活右手运动及感觉功能相关脑区，兴奋局部大脑皮质，产生一定促醒效应。     

血氧水平依赖功能磁共振成像技术分析正常成人痛觉相关皮层中枢的分布及量化特征

目的 应用血氧水平依赖功能磁共振成像(BOLD-fMRI)技术,分析正常成人痛觉相关皮层中枢的分布及量化特征.方法 选取10名正常成人志愿者,测定其痛阈并给予利手和非利手腕部2倍痛阈的电刺激,同时进行脑功能BOLD-fMRI扫描,应用SPM5进行后处理获得脑功能图像和数据,对脑激活区进行定位并测定其体积、强度.结果 刺激利手时激活对侧Brodmann Area(BA)3、1、2区7例,BA40区5例,BA5、7区3例,BA9、10、11区3例,BA6、8区2例,激活同侧BA5、7区2例,BA9、10、11区2例,BA6、8区3例;刺激非利手时激活对侧BA3、1、2区7例,BA40区6例,BA5、7区3例,BA9、10、11区2例,BA6、8区1例,激活同侧BA5、7区3例,BA9、10、11区1例,BA6、8区2例.3例在刺激两侧时BA3、1、2区和BA5、7区均没有激活,刺激利手时激活对侧BA40区2例、BA6区2例、前额叶皮质1例,刺激非利手时激活对侧BA40区2例、BA6区1例、前额叶皮质1例.结论 痛觉刺激可同时激活一般躯体感觉中枢、缘上回、辅助运动区、边缘系统等相关的皮层中枢,从而引发情绪、认知和内脏系统以及躲避反应等一系列相关活动.     

穴位TENS对正常年轻人热痛阈特异性抑制作用的研究

目的：探讨经皮神经电刺激疗法（TENS）对人体实验性热痛阈及实验性振动阀的影响，从而阐明TENS作用机理。方法：20名正常人，年龄在20－39岁，随机分为TENS组和空白刺激组，每位受试者左手合谷穴和大鱼际区接受30min，TENS（200us,100Hz,2-3倍感觉阈）或空白刺激，分别采用Medoc TSA 2001和Medoc VSA-300对受试者左手鱼际区的热痛阈和振动阈进行测定，并分析在TENS或空白刺激前的30，20，10min及刺激后0，10，20，30，40，50min记录热痛阈和振动阈，采用逐步回归分析法对结果进行分析。结果：本研究显示与空白刺激相比，30min的TENS治疗后即刻，即0min(P=0.002)和20min(P=0.004)热痛阈显著增高，增高值分别为0．81℃和1．54℃。而同一治疗方案在同一人群中对振动阈无改变。结论：TENS作用于针灸穴位具有镇痛的特异性，而对其他感觉如振动觉无改变。换言之，TENS可能通过激活粗纤维传导，抑制细胞传导的痛觉，从而达到镇痛的作用。     

刺激下肢穴位对吞咽中枢——岛叶皮质的激活效应:功能性磁共振成像的研究

目的 研究刺激不同下肢穴位对岛叶皮质的激活效应.方法 纳入健康右利手受试者20例接受功能性磁共振成像(fMRI).采用3T磁共振成像系统采集全脑功能像.扫描时受试者放松闭眼,但不能入睡.穴位刺激采用组块方式.采用一块海绵以2 Hz频率分别刷拂右下肢不同穴位.以SPM5软件包分析数据,采用混合效应模型进行组分析,以小范围...     

汉语及图片语义加工机制的fMRI研究

目的利用功能磁共振成像(fMRI)技术探讨汉字及图片语义加工的脑机制。方法对13名正常青年受试者进行视觉方式呈现汉字及图片语义辨别任务的fMRI扫描,采用AFNI软件进行数据分析和脑功能区活动图像。结果fMRI显示两种任务均激活了左侧顶下小叶、额中回、额下回、右侧小脑及双侧梭状回、舌回、枕中回、枕下回、辅助运动区。其中左侧顶下小叶、额中回及双侧枕中回、梭状回在图片语义辨别任务激活明显强于汉字任务,有显著性差异(P<0.05)。结论汉字及图片语义的脑加工均存在偏侧化现象,图片语义的脑处理有更多的脑活动参与完成。     

人脑运动皮层功能磁共振成像研究

目的采用功能用磁共振成像（fMRI）回波平面（EPI）技术,研究人脑运动皮质血氧水平依赖（BOLD）的功能磁共振成像。方法27名正常健康志愿者,右手挤压橡皮圈,在运动和静止两种对比条件下,采集运动皮层的回波平面图像（BOLD-fMRI）。分析运动状态和非运动状态信号对比的脑功能图像。结果fMRI图像显示运动刺激下脑功能活动激活区主要位于对侧感觉运动皮质区、辅助运动区等。结论fMRI可用于研究活体人脑各功能区的活动,fMRI可对运动刺激下的人脑运动皮质进行初步定位。     

Low intensity vagal nerve stimulation lowers human thermal pain thresholds

The effect of vagal nerve stimulation (VNS) on thermal pain sensation was studied in eight subjects who had vagal nerve stimulators surgically implanted for purposes of seizure control. Prior to their involvement in the study, all subjects had the intensity of their VNS (30 Hz, 0.5 ms, 1.0-2.75 mA) adjusted upwards until achieving their desired clinical effect of reduced seizures. Thermal pain thresholds were determined using a Medoc TSA-2001 with a thermode applied to the skin of the forearm. During VNS at settings 100% of those used clinically to control their seizures, subjects showed a statistically significant decrease in their thermal pain threshold of 1.1+/-0.4 degrees C. Acute effects of graded VNS on thermal pain thresholds were determined in seven of the subjects after cessation of chronic VNS. Two thermal threshold measurements were obtained while the subject received sham stimulation (0 mA intensity), during tactile control stimulation and during 30 s of VNS at intensities approximately 33, 66 and 100% of the settings utilized to control their seizures. Tactile control stimulation was provided by electrical stimulation of the skin of the ankle with the intensity adjusted by the patient to match the intensity of any sensations felt in the neck during VNS. Subjects were not aware of the settings employed. Their stimulator was adjusted with each trial and an ascending/descending ordering of intensity was utilized with an inter-trial interval of 2 min. Thermal pain thresholds were significantly decreased in relation to tactile control stimulation at all intensities of VNS tested with the greatest effect occurring at the 66% level. Subjects were also monitored non-invasively and hemodynamic responses to VNS were determined. No significant alterations in hemodynamic variables were observed. The findings of this human study are consistent with experiments in non-human animals which demonstrate a pro-nociceptive effect of low intensity VNS.     

CBF changes during brain activation: fMRI vs. PET

The changes in regional cerebral blood flow (rCBF) associated with the changes in neuronal activity are routinely measured both by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) techniques. However, direct comparison has not been performed to determine similarities and differences of PET and fMRI techniques in determining the rCBF response to brain activation. In the present study, a quantitative comparison of the functional rCBF maps obtained by PET and fMRI are made by performing an activation study in a single group of subjects under precisely controlled conditions and using identical visual stimuli. Twelve healthy volunteers participated in the activation study using the visual checkerboard stimulation with flip frequency at 8 Hz. By selecting the conjunctive pixels which activated on both PET and fMRI maps, the change in rCBF measured by fMRI was 36.95 +/- 2.54%, whereas the value measured by PET was 38.79 +/- 2.63%. Our results have demonstrated that there is no statistically significant difference (P = 0.22) in the measurements of rCBF change between MRI and PET methods.     

Die Erhöhung der Schmerzschwelle Durch Calcitonin

A randomized, double-blind study was performed to test the analgesic effect of salmon calcitonin (sCT). The pain threshold of ten healthy subjects was measured during electrical stimulation of the dental pulp. Each subject underwent four different tests, whereby sCT at doses of 50 IU, 100 IU and 200 IU or placebo was administered subcutaneously. For all subjects, four curves were obtained that showed the time course of the intensity of electrical stimulation needed to attain the pain threshold, up to 240 min post-application. Parallel to these studies, radioimmunoassay was performed to determine the plasma level at the time at which the maximum concentration was expected, i.e. 15 min after the injection. The pain threshold was raised by 10 mA or more with all three doses of calcitonin tested. The latent period before the threshold had risen by 10 mA declined in parallel with the doses of sCT administered (from 82 to 40+min), whereas the duration of action was increased (from 95 to over 182 min). The maximal threshold change was also significantly dependent on the dosage: with placebo the maximal change was 4 mA, while with sCT 50, sCT 100, and sCT 200 it was 14, 17 and 18 mA, respectively. The plasma levels of sCT and its analgesic activity were significantly correlated, as was demonstrated by means of linear regression based upon the bilogarithmic transformation of the plasma concentration. Altogether, the results prove conclusively that calcitonin given systemically possesses primary analgesic efficacy, a property that fits well into its spectrum of activity in the treatment of (painful) bone diseases.     

Cross-modal plasticity for sensory and motor activation patterns in blind subjects

Experimental data on cortical reorganization in blind subjects using H(2)(15)O positron emission tomography and functional magnetic resonance imaging (fMRI) showed activation of the visual cortex related to Braille reading and tactile discrimination tasks in congenitally and early blind subjects. The purpose of our study was to differentiate whether occipital activation of blind subjects during Braille reading is task specific or only triggered by sensory or motor area activation. Twelve congenitally and early-onset blind subjects were studied with fMRI during Braille reading, discriminating nonsense dots, sensory stimulation with electromagnetic pulses, and finger tapping. All experiments were performed utilizing a block design with 6 active epochs alternating with 6 rest conditions lasting 34 s each. Echo-planar imaging sequences with 34 transversal slices were performed on a 1.5-T MR scanner. All blind individuals reading Braille and discriminating nonsense dots showed robust activation of the primary, secondary, and higher visual cortex. Application of peripheral electrical stimuli to the reading hand revealed expected sensory activation of the primary somatosensory cortex, but no activation in the visual cortex. Pure motor activation during finger tapping with the reading hand showed expected precentral activation and no activation of visual cortex. In conclusion, occipital activation during Braille reading and discrimination tasks is not due to plasticity of sensory or motor function; pure motor or sensory tasks do not lead to an activation of striate cortex. The brain learns to differentiate between "finger touching" and "finger reading." Our results suggest that activation of the visual cortex in blind subjects is related to higher and more complex brain functions.     

Is mechanical pain threshold after transcutaneous electrical nerve stimulation (TENS) increased locally and unilaterally? A randomized placebo‐controlled trial in healthy subjects

Background and Purpose . It is not fully understood how transcutaneous electrical nerve stimulation (TENS) intensity affects mechanical pain threshold. Method . Sixty‐six healthy volunteers (13 male, 53 female; 132 hands) without prior experience of TENS participated in the study, which comprised a randomized single‐blind controlled trial. TENS was administered for 20 minutes through electrodes (25 × 25 mm) placed on the hands and forearms with a fixed frequency of 100 Hz and pulse duration of 150 µs. TENS intensity was randomized and allocated in a concealed manner so that one arm received TENS with stimulation intensity set at participants' subjective sensory threshold and the other received TENS with stimulation intensity continuously adjusted by physiotherapists to a strong but comfortable non‐painful stimulation. Observers were blinded to stimulation intensity levels. Results . Mechanical pain threshold increased significantly, by a mean total of 0.79 kg/cm² (95% confidence interval [95% CI]: 0.54–1.04) (p < 0.001) on the strong but comfortable non‐painful stimulation side. The mean change in mechanical pain threshold on the sensory threshold side was 0.19 kg/cm² and did not reach statistical significance (95% CI–0.15 to 0.51). The mean stimulation intensity level for sensory threshold was 6.7 mA (95% CI: 5.65 to 7.83) which was significantly lower (p < 0.001) than the mean stimulation intensity for the strong stimulation, which was 20.5 mA (95% CI 16.6 to 24.4), respectively. The strong stimulation levels were, on average, 3.05 times higher than sensory threshold, but individual variations were large (range 1.2–6.1). Conclusions . TENS administered at a strong but comfortable non‐painful stimulation intensity increases mechanical pain threshold ipsi‐laterally in healthy subjects, whereas TENS administered at sensory threshold intensity does not. TENS may be ineffective if electrodes are placed contralaterally or distant to the pain site and if stimulation intensity levels are not titrated to subjective strong levels. Further clinical trials are needed to clarify if these findings may also be generalized to populations of chronic pain sufferers. Copyright © 2007 John Wiley & Sons, Ltd.     

BOLD and blood volume-weighted fMRI of rat lumbar spinal cord during non-noxious and noxious electrical hindpaw stimulation

Spinal cord fMRI is a useful tool for studying spinal mechanisms of pain, hence for analgesic drug development. Its technical feasibility in both humans and rats has been demonstrated. This study investigates the reproducibility, robustness, and spatial accuracy of fMRI of lumbar spinal cord activation due to transcutaneous noxious and non-noxious electrical stimulation of the hindpaw in alpha-chloralose-anesthetized rats. Blood oxygenation level-dependent (BOLD) and blood volume-weighted fMRI data were acquired without and with intravenous injection of ultra small superparamagnetic iron oxide particles (USPIO), respectively, using a gradient echo (GE) echo planar imaging (EPI) technique at 4.7 T. Neuronal activation in the spinal cord induced by noxious stimulation to the hindpaw (2 ms wide, 5 mA amplitude, known to activate C-fibers) can be robustly detected by both fMRI techniques with excellent reproducibility and peaked at the stimulus frequency of 40 Hz. However, both fMRI techniques were not sensitive to neuronal activation in spinal cord induced by non-noxious stimulation (0.3 ms, 1.5 mA, known only to activate A-fibers). Spatially, the fMRI signal extended approximately 5 mm in the longitudinal direction, covering L(3)-L(5) segments. In the cross-sectional direction, the highest signal change of blood volume-weighted fMRI was in the middle of the ipsilateral dorsal horn, which roughly corresponds to laminae V and VI, while the highest signal change of BOLD fMRI was in the ipsilateral dorsal surface. This study demonstrates that spinal cord fMRI can be performed in anesthetized rats reliably and reproducibly offering it as a potential tool for analgesic drug discovery.     

fMRI观察电刺激麻木感对正常人中枢神经系统的影响

目的 观察电刺激麻木感对正常人中枢神经系统的影响。方法 对22名健康受试者以电刺激仪于右侧脚踝上方建立低频率及高频率电刺激麻木感模型，记录其对不同电刺激的麻木感评分和情绪效价评分；采集任务态血氧水平依赖fMRI（BOLD-fMRI），比较低频率及高频率电刺激下麻木感及情绪效价评分的差异，经分析获得不同频率电刺激下脑激活强度显著差异的脑区，比较不同强度电刺激下脑激活区激活效应值差异，分析高频电刺激下麻木感与情绪效价评分的关系。结果 不同频率电刺激下，受试者麻木感评分（t=13.18）及情绪效价评分（t=10.77）差异均有统计学意义（P均<0.01）。高频电刺激下，麻木感与效价评分呈负相关（r=-0.53，P=0.01）。不同电刺激下脑激活强度存在差异显著脑区包括左侧岛叶顶盖、左侧中扣带回、左侧颞叶、右侧顶叶岛盖、左侧中央后回、右侧中央岛盖、右侧岛叶后部及左侧丘脑，其激活效应值差异均有统计学意义（P均<0.05）。结论 电刺激麻木感可激活正常人左侧岛叶顶盖、左侧中扣带回、左侧颞叶、右侧顶叶岛盖、左侧中央后回、右侧中央岛盖、右侧岛叶后部及左侧丘脑；组块设计BOLD-fMRI可用于检测麻木感相关脑区活动。     

Motion or activity: their role in intra- and inter-subject variation in fMRI

Functional MRI (fMRI) carries the potential for non-invasive measurements of brain activity. Typically, what are referred to as activation images are actually thresholded statistical parametric maps. These maps possess large inter-session variability. This is especially problematic when applying fMRI to pre-surgical planning because of a higher requirement for intra-subject precision. The purpose of this study was to investigate the impact of residual movement artefacts on intra-subject and inter-subject variability in the observed fMRI activation. Ten subjects were examined using three different word-generation tasks. Two of the subjects were examined 10 times on 10 different days using the same paradigms. We systematically investigated one approach of correcting for residual movement effects: the inclusion of regressors describing movement-related effects in the design matrix of a General Linear Model (GLM). The data were analysed with and without modeling the residual movement artefacts and the impact on inter-session variance was assessed using F-contrasts. Inclusion of motion parameters in the analysis significantly reduced both the intra-subject as well as the inter-subject-variance.     

Stability and reliability of detection thresholds for human A-Beta and A-delta sensory afferents determined by cutaneous electrical stimulation

Activity in primary afferent fibers that usually mediate fine touch can evoke sensations of pain in conditions in which there is sensitization of central neurons. Input from these large diameter Abeta afferents may also sustain and exacerbate these central mechanisms. The role of these fibers in clinical pain syndromes can be evaluated by applications of electrical stimuli that preferentially activate Abeta axons. This study assessed the stability and reliability of a method of electrical stimulation (ES) useful for clinical evaluation. Monopolar constant-current rectangular pulses were delivered to 5 equi-spaced sites on the volar aspect of the left forearm along a transverse line 5 cm distal to the antecubital crease. Current intensity was gradually increased to determine detection threshold and pain detection threshold. This study determined: 1) Effect of pulse duration (1, 2, and 5 msec); 2) the variation of detection threshold and pain threshold over repeated stimulation; 3) the effect of electrode position with respect to distance from the trunk of underlying ulnar or median nerves; and 4) the effect of re-positioning the electrode on variability of detection threshold and pain threshold. There was no significant variability over time for either detection threshold (DT) or pain threshold (PT) at any of the 3 pulse durations tested. There was also no significant effect on variability of shifting the electrode between sites, nor was there a significant difference in variability between sites when placed either over or adjacent to peripheral nerves. Under simulated clinical conditions of electrode re-positioning, the mean detection threshold in 300 trials and ten subjects was 0.30 mA with an overall standard error of 0.007, standard errors of 0.014 over the 10 subjects, 0.003 over the 6 trials, and 0.012 over the 5 locations. Similarly, mean pain threshold in these 300 trials was 3.24 +/- 0.093, with standard errors of 0.12 over the 10 subjects, 0.023 over the 6 trials, and 0.13 over the 5 locations. Mean ratio of pain threshold divided by detection threshold ratio was 10.9 +/- 0.25 with a range of 2.0-28.3. Single pulse, constant current electrical stimulation of the skin at threshold levels is a quantifiable and reliable sensory method that is repeatable within and between testing sessions. Our results suggest that in skin unaffected by allodynia, a ratio of the two sensory thresholds (pain threshold and detection threshold) of less than 2.0 is uncommon. We propose that, in the presence of mechanical allodynia, a pain threshold/detection threshold of less than 2.0 suggests that altered central nervous system processing of Abeta input may contribute to allodynia.     

Functional magnetic resonance image finding of cortical activation by neuromuscular electrical stimulation on wrist extensor muscles

OBJECTIVE: To investigate the effects that neuromuscular electrical stimulation on the wrist extensor muscles have on the cerebral cortex. DESIGN: A functional magnetic resonance imaging study was performed on eight normal volunteers. The activation task was the maximum wrist extension by neuromuscular electrical stimulation, applied through a two-channel electrical stimulator. Monophasic square-wave pulses were used. The activation maps were generated by the threshold test maps. The level of primary motor cortex and primary sensory cortex activations was estimated. RESULTS: Among the eight subjects, seven showed significant activation on contralateral primary sensorimotor cortex by neuromuscular electrical stimulation on the wrist extensor muscles. In these seven subjects, additional bilateral or contralateral supplementary motor area activations were also observed. The number of activated pixels on the primary sensory cortex was slightly greater than that on the primary motor cortex. CONCLUSION: Neuromuscular electrical stimulation, when applied to the peripheral muscles, seems to have a direct effect on the cerebral cortex.