Dynamics of brain activity in motor and frontal cortical areas during music listening: a magnetoencephalographic study

There are formidable problems in studying how 'real' music engages the brain over wide ranges of temporal scales extending from milliseconds to a lifetime. In this work, we recorded the magnetoencephalographic signal while subjects listened to music as it unfolded over long periods of time (seconds), and we developed and applied methods to correlate the time course of the regional brain activations with the dynamic aspects of the musical sound. We showed that frontal areas generally respond with slow time constants to the music, reflecting their more integrative mode; motor-related areas showed transient-mode responses to fine temporal scale structures of the sound. The study combined novel analysis techniques designed to capture and quantify fine temporal sequencing from the authentic musical piece (characterized by a clearly defined rhythm and melodic structure) with the extraction of relevant features from the dynamics of the regional brain activations. The results demonstrated that activity in motor-related structures, specifically in lateral premotor areas, supplementary motor areas, and somatomotor areas, correlated with measures of rhythmicity derived from the music. These correlations showed distinct laterality depending on how the musical performance deviated from the strict tempo of the music score, that is, depending on the musical expression.     

The influence of music and music therapy on pain-induced neuronal oscillations measured by magnetencephalography

Modern forms of music therapy are clinically established for various therapeutic or rehabilitative goals, especially in the treatment of chronic pain. However, little is known about the neuronal mechanisms that underlie pain modulation by music. Therefore, we attempted to characterize the effects of music therapy on pain perception by comparing the effects of 2 different therapeutic concepts, referred to as receptive and entrainment methods, on cortical activity recorded by magnetencephalography in combination with laser heat pain. Listening to preferred music within the receptive method yielded a significant reduction of pain ratings associated with a significant power reduction of delta-band activity in the cingulate gyrus, which suggests that participants displaced their focus of attention away from the pain stimulus. On the other hand, listening to self-composed “pain music” and “healing music” within the entrainment method exerted major effects on gamma-band activity in primary and secondary somatosensory cortices. Pain music, in contrast to healing music, increased pain ratings in parallel with an increase in gamma-band activity in somatosensory brain structures. In conclusion, our data suggest that the 2 music therapy approaches operationalized in this study seem to modulate pain perception through at least 2 different mechanisms, involving changes of activity in the delta and gamma bands at different stages of the pain processing system.     

The perception of pain in others suppresses somatosensory oscillations: a magnetoencephalography study

Accumulating evidence demonstrates that similar neural circuits are activated during the first-hand experience of pain and the observation of pain in others. However, most functional MRI studies did not detect signal change in the primary somatosensory cortex during pain empathy. To test if the perception of pain in others involves the primary somatosensory cortex, neuromagnetic oscillatory activity was recorded from the primary somatosensory cortex in 16 participants while they observed static pictures depicting body parts in painful and non-painful situations. The left median nerve was stimulated at the wrist, and the poststimulus rebounds of the approximately 10-Hz somatosensory cortical oscillations were quantified. Compared to the baseline condition, the level of the approximately 10-Hz oscillations was suppressed during both of the observational situations, indicating the activation of the primary somatosensory cortex. Importantly, watching painful compared to non-painful situations suppressed somatosensory oscillations to a significant stronger degree. In addition, the suppression caused by perceiving others in the painful relative to the non-painful situations correlated with the perspective taking subscale of the interpersonal reaction index. These results, consistent with the mirror-neuron system, demonstrate that the perception of pain in others modulates neural activity in primary somatosensory cortex and supports the idea that the perception of pain in others elicits subtle somatosensory activity that may be difficult to detect by fMRI techniques.     

Transdural motor cortex stimulation reverses neuropathic pain in rats: A profile of neuronal activation

Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos‐IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos‐IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain.     

ICA-based spatiotemporal approach for single-trial analysis of postmovement MEG beta synchronization

The extraction of event-related oscillatory neuromagnetic activities from single-trial measurement is challenging due to the non-phase-locked nature and variability from trial to trial. The present study presents a method based on independent component analysis (ICA) and the use of a template-based correlation approach to extract Rolandic beta rhythm from magnetoencephalographic (MEG) measurements of right finger lifting. A single trial recording was decomposed into a set of coupled temporal independent components and corresponding spatial maps using ICA and the reactive beta frequency band for each trial identified using a two-spectrum comparison between the postmovement interval and a reference period. Task-related components survived dual criteria of high correlation with both the temporal and the spatial templates with an acceptance rate of about 80%. Phase and amplitude information for noise-free MEG beta activities were preserved not only for optimal calculation of beta rebound (event-related synchronization) but also for profound penetration into subtle dynamics across trials. Given the high signal-to-noise ratio (SNR) of this method, various methods of source estimation were used on reconstructed single-trial data and the source loci coherently anchored in the vicinity of the primary motor area. This method promises the possibility of a window into the intricate brain dynamics of motor control mechanisms and the cortical pathophysiology of movement disorder on a trial-by-trial basis.     

The occipital cortex is hyperexcitable in migraine: experimental evidence

OBJECTIVES: Threshold for generation of magnetophosphenes has been reported to be lower in migraine. We compared the threshold for eliciting phosphenes by transcranial magnetic stimulation and the ability to visually trigger headache in a select group of individuals with migraine with and without aura to normal controls. METHODS: Transcranial magnetic stimulation was performed using the Cadwell MES-10 stimulator. A circular coil, 9.5 cm in diameter, was applied to the occipital scalp (7 cm above the inion). Stimulator intensity was increased in 10% increments until subjects reported visual phenomena or 100% intensity was reached. Stimulator intensity was then fine-tuned to determine the threshold at which phosphenes were seen. In the same subjects, visual stimulation was given in 3.0 T MRI and if a headache occurred the response was recorded. RESULTS: Fifteen subjects with migraine were compared to 8 controls. A significant proportion of the migraineurs (86.7%) developed phosphenes compared to the controls (25%) (P = .006). The probability of triggering a headache was also higher in the migraineurs (53%); no headache was triggered in the controls (P = .019). A significant correlation was found between the threshold for phosphenes on transcranial magnetic stimulation and visually triggered headache (P = .002). When only migraine was considered, there was again a significant trend (P = .084). CONCLUSIONS: There is a difference in threshold for excitability of occipital cortex in migraineurs and controls. The hyperexcitable visual cortex in migraine is predisposed to visually triggered headache.     

利用fMRI和双手交替运动模式研究脑肿瘤所致的运动功能重组

目的应用fMRI研究双手交替运动模式下中央沟附近脑肿瘤患者运动功能重组的方式及特征.方法6名正常受试者和14名脑肿瘤患者采用双手交替对指运动模式行fMRI扫描,比较正常受试者与脑肿瘤患者脑激活的异同.结果正常人单手对指运动主要激活运动手对侧的大脑半球和同侧小脑半球.脑肿瘤患者非受累手运动所致的激活与正常受试者基本相同;而当受累手运动时,则出现运动功能的重组,包括肿瘤对侧正常半球内M1区的代偿性激活、肿瘤侧半球MI活动的减弱、双侧SMA等次级运动中枢激活区的增大以及双侧小脑半球的激活.结论采取双手交替运动模式,fMRI不仅显示了受累侧运动区的变形与移位,而且揭示了一种新的功能重组模式,即运动功能重组可能涉及分布于全脑的整个神经网络.     

The multifaceted nature of the relationship between performance and brain activity in motor sequence learning

The ‘learning and performance’ conundrum has for a long time puzzled the field of cognitive neuroscience. Deciphering the genuine functional neuroanatomy of motor sequence learning, among that of other skills, has thereby been hampered. The main caveat is that changes in neural activity that inherently accompany task practice may not only reflect the learning process per se, but also the basic motor implementation of improved performance. Previous research has attempted to control for a performance confound in brain activity by adopting methodologies that prevent changes in performance. However, blocking the expression of performance is likely to distort the very nature of the motor sequence learning process, and may thus represent a major confound in itself. In the present study, we postulated that both learning-dependent plasticity mechanisms and learning-independent implementation processes are nested within the relationship that exists between performance and brain activity. Functional magnetic resonance imaging (fMRI) was used to map brain responses in healthy volunteers while they either (a) learned a novel sequence, (b) produced a highly automatized sequence or (c) executed non-sequential movements matched for speed frequency. In order to dissociate between qualitatively distinct, but intertwined, relationships between performance and neural activity, our analyses focused on correlations between variations in performance and brain activity, and how this relationship differs or shares commonalities between conditions. Results revealed that activity in the putamen and contralateral lobule VI of the cerebellum most strongly correlated with performance during learning per se, suggesting their key role in this process. By contrast, activity in a parallel cerebellar network, as well as in motor and premotor cortical areas, was modulated by performance during learning and during one or both control condition(s), suggesting the primary contribution of these areas in motor implementation, either as a function or not of the sequential content of movements. Our findings thus highlight the multifaceted nature of the link between performance and brain activity, and suggest that different components of the striato-cortical and cerebello-cortical motor loops play distinct, but complementary, roles during early motor sequence learning.     

Assessment of motor function in people with multiple sclerosis

Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system (CNS) which predominantly affects young adults. In order to provide physiotherapy appropriate to the needs of individuals with MS, it is necessary to assess and evaluate the nature and degree of motor and functional deficits. The aim of this research was to develop a physiotherapy assessment which would consistently and objectively evaluate motor function in people with MS. The Motor Club Assessment (MCA), originally developed for use in stroke patients, was identified as exhibiting several features which were consonant with the required criteria. It was therefore modified for use in MS. The Amended MCA (AMCA) was tested for inter-rater agreement, which was found to be good for the lower limb motor section (weighted kappa = 0.80), the upper limb motor section (weighted kappa = 0.90), and the functional activities section (weighted kappa = 0.92). The internal consistency was high for the lower limb section (alpha = 0.97) and the functional activities section (alpha = 0.92), but could not be determined for the upper limb section due to a clear ceiling effect. The study demonstrated that the AMCA is a valid tool for assessment use by physiotherapists in MS patients, and that it has an acceptable level of reliability when used in a clinic setting by physiotherapists suitably experienced in the treatment of neurological patients.     

The role of cardiovascular activity in fibromyalgia and conditioned pain modulation

Fibromyalgia (FM) is a chronic widespread pain condition of unknown origin. Reduced endogenous pain inhibition could be related to high pain sensitivity in FM. Associations between conditioned pain modulation (CPM) and cardiovascular responses to pain have been observed in healthy subjects (HS). Because reduced cardiovascular reactivity to various stressors has been reported in FM patients, we investigated relationships between CPM and cardiovascular response to the cold pressor test (CPT) in 22 FM patients and 25 HS. CPM was evaluated by comparing pain intensity produced by a 120-second heat test stimulus (HTS) before and after a CPT (2 minutes, 12°C). The CPT, used to activate CPM, produced greater pain intensity in FM patients. Patients with FM had higher heart rates than HS at baseline and during CPT. Higher heart rate was related with higher pain intensity during the CPT. Blood pressure increments during CPT were weaker in the FM group. CPM was less effective in FM patients than in HS. Importantly, systolic blood pressure responses during CPT were positively related to CPM effectiveness, suggesting that reduced blood pressure response during the conditioning stimulus could be involved in CPM dysfunction in the FM group. Higher heart rate could be implicated in the greater sensitivity to cold pain in FM. Patients with FM have reduced blood pressure response to a painful CPT. Reduced cardiovascular reactivity to pain could have important involvement in diminished endogenous pain inhibition efficacy and FM pathophysiology.     

The relationship between frailty and motor function among living in the community elderly females

[Purpose] This study aimed to investigate the prevalence of frailty among community-dwelling elderly females, and to examine its relation to motor function and the main risk factors of frailty. [Participants and Methods] The participants were 67 community-dwelling elderly females, aged 76.2 ± 7.7 years. We performed measurements of physical parameters, motor functions (such as grip strength), timed up and go test (TUG), walking speed, and frailty (measured using the Kihon Checklist [KCL]). [Results] KCL scores were 31.3%, 31.3%, and 37.3% in the frailty, pre-frailty, and robust groups, respectively. The frailty group was older than the pre-frailty and robust groups. Additionally, the different groups showed significant differences in grip strength, TUG, and walking speed. The highest median KCL score was for depression, followed by physical function. As a results, frailty was evident even among health-conscious elderly people. [Conclusion] It is essential to identify frailty at an early stage and identify its preventive factors, in order to extend the healthy life expectancy of the local population.     

The Buffering analysis to identify common geographical factors within the vicinity of severe injury related to motor vehicle crash in Malaysia

BACKGROUND: The main objective was to identify common geographical buildup within the 100-meter buffer of severely injured based on injury severity score (ISS) among the motor vehicle crash (MVC) victims in Malaysia.METHODS: This was a prospective cohort study from July 2011 until June 2013 and involved all MVC patients attending emergency departments (ED) of two tertiary centers in a district in Malaysia. A set of digital maps was obtained from the Town Planning Unit of the district Municipal Office (local district map). Vector spaces were spanned over these maps using GIS software (ARCGIS 10.1 licensed to the study center), and data from the identified severe injured cases based on ISS of 16 or more were added. Buffer analysis was performed and included all events occurring within a 100 -meter perimeter around a reference point.RESULTS: A total of 439 cases were recruited over the ten-month data collection period. Fifty two (11%) of the cases were categorized as severe cased based on ISS scoring of 16 and more. Further buffer analysis looking at the buildup areas within the vicinity of the severely injured locations showed that most of the severe injuries occurred at locations on municipal roads (15, 29%), straight roads (16, 30%) and within villages buildup (suburban) areas (18, 35%).CONCLUSION: This study has successfully achieved its objective in identifying common geographical factors and buildup areas within the vicinity of severely injured road traffic cases.     

神经节苷脂治疗大鼠脊髓半切综合征运动功能恢复的机制

目的单唾液酸四己糖神经节苷脂(GM-1)可促进神经再生,有助于运动功能恢复,评价GM-1对颈髓半切综合征(BSS)的治疗效果。方法取SD大鼠55只,随机抽签法分成对照组、损伤组、治疗组;直视下半切大鼠颈髓1/2C5-7阶段;治疗组在伤后15,90,180min,2,3d分别腹腔内注射GM-110mg/kg,损伤组注射生理盐水。伤后1,6,24h,1,6周时各取损伤组合治疗组大鼠各2只伤区颈髓组织送光镜和电镜检查,并进行Rivlin斜板试验以评价大鼠运动功能。结果正常对照组大鼠在自制斜板上停留的最大角度为82°,损伤组术后1周平均为55°,6周时有一定程度的增加65°;而治疗组术后增加较快,6周时接近正常。治疗组半切处出血减轻,周围白质大部相连,髓鞘修复,大量重组的少突胶质细胞增生,运动功能恢复90%。结论GM-1对BSS脊髓有保护作用,并促进其恢复。     

多种神经节苷脂与小分子多肽对大鼠脊髓损伤后自由基及运动诱发电位的影响

目的研究多种神经节苷脂与小分子多肽对脊髓损伤大鼠自由基及运动诱发电位的影响,探讨神经功能恢复的机制。方法96只雌性Wistar大鼠随机分为四组:A组作为正常组,B、C、D组按Allen’s法制作大鼠脊髓外伤模型。损伤后,B、C组注射不同剂量神经节苷脂与小分子多肽复合物,D组不进行治疗。各组大鼠在损伤后第1、7、14、21、28天测定斜板运动评分及运动诱发电位,之后取受损脊髓组织测定丙二醛含量。结果与D组比较,B、C两组的丙二醛含量显著降低,同时治疗组的运动诱发电位和运动功能也恢复得更快。结论多种神经节苷脂与小分子多肽能够有效减轻脂质过氧化反应,改善运动诱发电位和运动功能。     

限制诱导运动疗法辅助虚拟现实游戏对偏瘫儿童运动功能的影响

目的 观察限制诱导运动疗法辅助虚拟现实游戏对偏瘫型脑性瘫痪（脑瘫）患儿运动功能的影响。 方法 采用随机数字表法将偏瘫型脑瘫患儿50例随机分为对照组和实验组,每组25例。2组患儿均给予常规康复治疗,对照组每日行限制诱导运动疗法4 h,其中1 h在治疗师帮助下行受累侧作业治疗,另外3 h在患儿监护人帮助下完成日常生活活动治疗。实验组1 h在治疗师帮助下治疗,1 h进行虚拟现实游戏,剩余2 h在患儿监护人帮助下完成日常生活活动治疗。2组儿童均每周治疗5 d,连续治疗3周。于治疗前、治疗3周后（治疗后）采用上肢功能质量测试量表（QUEST)、中文版粗大运动功能测试量表(GMFM)、残疾儿童评估量表（PEDI）分别对2组患儿的上肢运动功能、粗大运动功能、整体社会功能进行评定。 结果 治疗后,2组患儿的QUEST、GMFM和PEDI评分与组内治疗前比较,差异均有统计学意义(P<0.01),且实验组治疗后的QUEST、GMFM和PEDI评分分别为（16.38±7.07）分、（72.79±9.96）分、（59.05±5.36）分,均显著高于对照组,差异均有统计学意义(P<0.05)。 结论 限制诱导运动疗法辅助虚拟现实游戏能显著改善偏瘫型脑瘫患儿运动功能及整体社会功能。     

动能递进式运动对急性心肌梗死经皮冠状动脉介入术后患者早期运动功能的改善作用

目的 探讨动能递进式运动干预对急性心肌梗死经皮冠状动脉介入(percutaneous coronary intervention, PCI)术后患者早期运动功能的改善作用。 方法 选取2017年3月-2018年3月于我院接受PCI术治疗的急性心肌梗死患者84例作为观察对象,将其以随机抽签法分成实验组与对照组,每组各42例。对照组予以常规护理,实验组在对照组的基础上增用动能递进式运动干预。比较2组干预前后心功能(左心室射血分数、左心室舒张末期容积、左心室收缩末期容积)、早期运动功能、不良事件发生情况及患者生活质量。 结果 干预后,实验组左心室射血分数高于对照组(t=4.281,P＜0.001);运动时间、最大运动负荷、代谢当量水平均好于对照组(P＜0.05);不良事件发生率低于对照组(χ²=4.480,P=0.034),症状、躯体功能、心理社会功能、认知功能、满意度评分高于对照组(P＜0.05)。 结论 动能递进式运动干预可显著改善急性心肌梗死PCI术后患者早期运动功能,同时有利于改善患者心功能,降低不良事件发生风险,提高患者的生活质量。     

神经元兴奋性在右美托咪定保护老龄大鼠术后认知功能中的作用

目的探索神经元兴奋性在右美托咪定保护老龄大鼠术后认知功能中的作用。方法将SD老龄大鼠随机分为假手术组、生理盐水对照组、右美托咪定组。手术前30 min,右美托咪定组大鼠腹腔注射右美托咪定50μg/kg,假手术组和生理盐水对照组大鼠腹腔注射等量生理盐水。在麻醉状态下对右美托咪定和生理盐水组行右侧肾脏切除术,假手术组除不切除肾脏外,其余操作与前两组一致。术前1~4 d及术后1~7 d通过水迷宫检测大鼠的空间学习和记忆功能;术后1~7 d,分别采用免疫组织化学染色进行c-fos和TUNEL标记,酶联免疫吸附(ELISA)法检测海马脑区白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的含量,高效液相色谱检测海马脑区谷氨酸释放量。结果术前1~4d,三组大鼠寻找平台所需时长相比差异无统计学意义(P> 0. 05),且随着训练次数的增加,三组大鼠寻找到平台所用的时间均逐渐降低;术后1~7 d,假手术组相比,生理盐水对照组大鼠寻找平台潜时、脑区c-fos表达阳性面积百分比、神经元凋亡水平、海马脑区IL-1β和TNF-α含量以及谷氨酸释放量均显著增加(P <0. 05),而与生理盐水对照组相比,右美托咪定组以上指标均显著减少或降低(P <0. 05);术后,与假手术组相比,生理盐水对照组大鼠在平台在目标象限停留时间百分比显著降低(P <0. 001);而与生理盐水对照组相比,右美托咪定组大鼠在平台在目标象限停留时间百分比显著增加(P <0. 001);术后,右美托咪定组大鼠相关指标改善程度随药物作用时长而增强。结论术前注射右美托咪定可以通过降低神经元兴奋性对老龄大鼠术后认知功能起到保护作用,且其作用效果随作用时长增加而增加。     

The role of adenosine in the control of immune function

Summary In the past several years the study of primary immunodeficiencies has led to an explosive growth of basic information on the pathophysiology of the immune system. In 1972 a deficiency of adenosine deaminase (ADA) was described in two patients with severe combined immunodeficiency (SCID). Shortly thereafter, deficiencies of other enzymes involved in the purine salvage pathway (i.e., purine nucleoside phosphorylase and ecto-5′-nucleotidase) were described in association, respectively, with defective T- and B-lymphocyte activity. Although the exact biochemical mechanism(s) in these immunodeficiencies is not known, elevated levels of adenosine, 2-deoxyadenosine and their metabolites occur in these patients. Adenosine inhibitsin vitro lymphocyte proliferation, T-lymphocyte-mediated cytolysis, monocyte chemotaxis and basophil histamine release. We have found that adenosine increases lymphocyte cAMP levels, by interacting with a specific plasma membrane receptor which leads to the activation of adenylate cyclase. We have also explored the influence of adenosine in the control of histamine release from human basophils and have shown that adenosine inhibits the IgE-mediated release reaction. The action of adenosine on basophils also appears to be mediated by a specific cell-surface receptor. Adenosine also plays a central and complex role in the control of transmethylation reactions. These reactions modulate several immune and inflammatory reactions, including monocyte chemotaxis, lymphocyte mitogenesis, T-lymphocyte-mediated cytolysis, and probably the IgE-mediated release of histamine from basophils. Thus, adenosine may act as an endogenous modulator of immune function by two separate but interrelated effects: its ability to interact with a cell-surface adenosine receptor, and/or to influence intracellular methylation. This work was supported in part by grants HL 14153 from the Heart and Lung Institute, AI 07290 from the Institutes of Allergy and Infectious Disease, National Institutes of Health (Bethesda, Md) and from theConsiglio Nazionale dette Ricerche (CNR), Roma, Italy, grant no. 79.02392.65. This is publication # 387, O’Neill Research Laboratories, The Good Samaritan Hospital, 5601 Loch Raven Boulevard, Baltimore, Md 21239. Recipient of RCDA AI 00231 from the National Institutes of Health, Bethesda, Md.