成年大鼠健侧颈7移位术后跨大脑两半球功能重组的脑电生理研究

目的研究健侧颈7移位至患侧正中神经术后初级运动皮层跨大脑两半球功能重组的时程,初步探讨该重组的中枢机制。方法将45只SD雄性大鼠随机分为9组,即正常对照组(1个组),加左侧全臂丛根性撕脱模型和右侧(健侧)颈7移位模型两组在术后3个月、5个月、7个月、10个月共8个时间组,每组5只。采用运动皮层内微电极电刺激技术,定量评价成年大鼠患肢正中神经代表区在双侧初级运动皮层(初级运动皮层,MI)内的可塑性变化。结果在双侧MI电刺激:(1)正常对照组:一侧肢体的正中神经代表区只在其对侧MI出现。(2)左侧全臂丛根性撕脱模型:在术后3～10个月,患肢的正中神经代表区在双侧MI均能被诱发出来。(3)健侧颈7移位模型:术后3个月,患肢正中神经代表区在双侧MI均未出现。术后5个月,患肢正中神经代表区仅出现于患肢同侧MI。术后7个月,患肢正中神经代表区在双侧MI均出现。术后10个月,患肢正中神经代表区只出现于患肢对侧MI,代表区面积与正常对照无明显差异,且仍位于原前肢代表区。结论在健侧颈7移位成年大鼠模型上证实,在术后10个月初级运动皮层出现了跨大脑两半球的功能重组,并初步探讨了其可能的中枢机制。发现了成年哺乳动物周围神经解剖通路改变后发生跨大脑半球功能重组的脑电生理依据。     

Modulation of motor and premotor activity during imitation of target-directed actions

Behavioral studies reveal that imitation performance and the motor system are strongly influenced by the goal of the action to be performed. We used functional magnetic resonance imaging (fMRI) to assess the effect of explicit action goals on neural activity during imitation. Subjects imitated index finger movements in the absence and presence of visible goals (red dots that were reached for by the finger movement). Finger movements were either ipsilateral or contralateral. The pars opercularis of the inferior frontal gyrus showed increased blood oxygen level-dependent fMRI signal bilaterally for imitation of goal-oriented actions, compared with imitation of actions with no explicit goal. In addition, bilateral dorsal premotor areas demonstrated greater activity for goal-oriented actions, for contralateral movements and an interaction effect such that goal-oriented contralateral movements yielded the greatest activity. These results support the hypothesis that areas relevant to motor preparation and motor execution are tuned to coding goal-oriented actions and are in keeping with single-cell recordings revealing that neurons in area F5 of the monkey brain represent goal-directed aspects of actions.     

Contrasting properties of motor output from the supplementary motor area and primary motor cortex in rhesus macaques

The goal of this study was to assess the motor output capabilities of the forelimb representation of the supplementary motor area (SMA) in terms of the sign, latency and strength of effects on electromyographic (EMG) activity. Stimulus triggered averages of EMG activity from 24 muscles of the forelimb were computed in SMA during a reach-to-grasp task. Poststimulus facilitation (PStF) from SMA had two distinct peaks (15.2 and 55.2 ms) and one poststimulus suppression (PStS) peak (32.4 ms). The short onset latency PStF and PStS of SMA were 5.5 and 16.8 ms longer than those of the primary motor cortex (M1). The average magnitudes (peak increase or decrease above baseline) of the short and long latency PStF and PStS from SMA at 60 microA were 13.8, 11.3 and -11.9% respectively. In comparison, M1 PStF and PStS magnitudes at 15 microA were 50.2 and -23.8%. Extrapolating M1 PStF magnitude to 60 microA yields a mean effect that is nearly 15 times greater than the mean PStF from SMA. Moreover, unlike M1, the facilitation of distal muscles from SMA was not significantly greater than the facilitation of proximal muscles. We conclude that the output from SMA to motoneurons is markedly weaker compared with M1 raising doubts about the role of SMA corticospinal neurons in the direct control of muscle activity.     

大鼠健侧颈7移位术后运动皮层兴奋性谷氨酸及其受体变化

目的 探讨大鼠健侧颈7移位术后运动皮层兴奋性谷氨基酸及其受体变化规律.方法 建立颈胸椎后路左侧全臂丛根性撕脱伤和健侧颈7移位正中神经大鼠模型,分别于术后不同时间采用肌电图检测观察正中神经功能的恢复,同时运用运动皮层区微电极刺激法明确大鼠患肢皮层代表区在术后的变化.根据运动皮层区微电极刺激的结果,选择4个皮层重组特异时间点进行取材,行大鼠脑片初级运动皮层区谷氨酸神经元及N-甲基-D-天门冬氨酸受体(NR1、NR2A、NR2B)的免疫组织化学染色.结果 大鼠健侧颈7移位术后,随时间的延长,患侧指深屈肌复合肌肉动作电位潜伏期缩短,波幅升高.术后4个月组,5只大鼠中有3只患爪支配区仅位于同侧运动皮层,同时各手术组双侧运动皮层NR1表达水平均增高,与对照组相比差异有统计学意义(P<0.05).其中右侧运动皮层NR1表达升高显著,与同组对侧相比差异有统计学意义(P<0.05).术后7个月组,4只大鼠患爪支配区位于双侧运动皮层,而且各手术组右侧运动皮层NR2A表达水平升高,与健康大鼠同侧皮层或同组大鼠对侧皮层比较差异均有统计学意义(P<0.05),健侧颈7移位组大鼠右侧皮层NR2A表达水平,较单纯臂丛撕脱或臂丛撕脱健侧颈7切断组同侧皮层升高明显,差异有统计学意义(P<0.05).术后10个月组,3只大鼠患爪支配区位于对侧运动皮层,而在同侧运动皮层却未测到,同时健侧颈7移位组大鼠右侧皮层NR2A表达水平仍维持在升高水平,与其他各组大鼠同侧或同组对侧比较,差异有统计学意义(P<0.05).结论 大鼠全臂丛根性撕脱伤健侧颈7移位正中神经后,大脑发生跨两半球的功能重塑.NR1和NR2A表达的增高可能分别在术后初期和后期功能重组中发挥了一定的作用.     

Distinct causal influences of parietal versus frontal areas on human visual cortex: evidence from concurrent TMS-fMRI

It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level-dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1-V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1-V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex.     

Temporal relation of population activity in visual areas MT/MST and in primary motor cortex during visually guided tracking movements

There is growing evidence that in primate cerebral cortex the areas along the 'dorsal pathway' are involved in the transformation of visual motion information towards a motor command. To pursue this cortical flow of information from visual motion areas to the motor cortex, single-cell activity was recorded from visual areas MT/MST (middle temporal area/medial superior temporal area) and from primary motor cortex (M1) while monkeys tracked moving targets with their right hand. Spike activity of 353 directionally tuned motor cortex cells was combined to a time-varying population vector, and similarly a time-resolved visual population vector was calculated from 252 MT/MST cells. Both population vectors code faithfully for the direction of the collinear motion of target and hand. For a given direction, the length of the population vectors varied over time during the performance of the task. The temporal evolution of both population responses reflects the different relationship between the early visual responses to the moving target and the directional motor command controlling the hand movement. The results indicate that during the visual tracking task visual and motor populations which code for similar directions of movement are co-activated with considerable temporal overlap. Despite this co-activation in both modalities, we failed to observe any significant synchronization between areas MT/MST and M1.     

Dorsal root rhizotomy and avulsion in the cat: a comparison of long term effects on dorsal horn neuronal activity

We performed an extracellular microelectrode analysis of the neuronal activity of cells located in deeper laminae of dorsal horns that had been deafferented by ipsilateral lumbar dorsal root rhizotomy or avulsion. Special attention was given to those cells that were recorded in preparations that were more than 6 weeks chronic. We compared the results to those obtained in nondenervated controls and in experiments in which the spinal cord was acutely transected at a midthoracic level, but had intact dorsal roots. There was an increase in ipsilateral flank and contralateral input in the chronically deafferented as compared to nondenervated controls. Differences were observed between long term rhizotomized and avulsed dorsal horns. Receptive fields extended on to flank and thoracic dermatomes after rhizotomy, often requiring only light cutaneous stimuli. Receptive fields were more restricted with avulsion injury, generally requiring moderate to strong, superficial or deep pinch. Histological analysis revealed consistent differential damage to the medial portion of Lissauer's tract with avulsion injury and subsequently more gliosis in the substantia gelatinosa. The loss of this propriospinal pathway may explain the lack of receptive field expansion on to the thoracic dermatomes and the stronger natural stimuli that were required. A higher percentage of cells with bilateral and inhibitory receptive fields was found in experiments in which the spinal cord was transected at a midthoracic level than in the controls. Ipsilateral excitatory receptive fields were also expanded as compared with control observations, but were not found on the flank.(ABSTRACT TRUNCATED AT 250 WORDS)     

Validation and the future of stimulation therapy of the primary motor cortex

The use of electrical motor cortex stimulation (EMCS) for post-stroke pain was established in Japan and has spread globally. EMCS has been used for the treatment of neuropathic pain, Parkinson's syndrome, and recovery of motor paresis. Since 2000, repetitive transcranial magnetic stimulation (rTMS) has been developed for the treatment of various neurological disorders. rTMS is a non-invasive method with almost no adverse effects. In the USA, rTMS of the left dorsolateral prefrontal cortex was approved for the treatment of major depression in 2008. rTMS of the primary motor cortex (M1) has been studied worldwide for the treatment of neuropathic pain, Parkinson's disease, motor paresis after stroke, and other neurological problems. New methods and devices for rTMS therapy are under development, and rTMS of the M1 is likely to be established as an effective therapy for some neurological disorders. The present review discusses EMCS and rTMS of the M1 concisely.     

Reorganization in motor cortex after brachial plexus avulsion injury and repair with the contralateral C7 root transfer in rats

The purpose of our study was to establish the profile of cortical reorganization in whole BPAI on rats and evaluate changes of cortical reorganization after repair of the median nerve with the contralateral C7 root transfer. Forty adult SD rats underwent whole roots avulsion of left brachial plexus, among them 20 received contralateral C7 root transfer to the injured median nerve. Intracortical microstimulation was performed in primary motor cortex (M1) at intervals of 3, 5, 7, and 10 months, postoperatively. The maps of motor cortical responses were constructed. Five normal rats were used as the control. Results showed that stimulating right M1 elicited motion of left vibrissae, submaxilla, neck, back, and left hindlimb after left BPAI, among them neck representation area replaced the forelimb area throughout the reorganization process. The left forelimb representation area was found in the left motor cortex 5 months after the contralateral C7 root transfer and existed in both motor cortexes at 7th postoperative month. The left forelimb representation area was detected only in right motor cortex at 10th month, postoperatively. In conclusions, after the contralateral C7 root transfer for repair of the median nerve in BPAI, the cortical reorganization occurred in a time‐dependent reorganization. The findings from this study demonstrate that brain involves in the functional recovery after BPAI and repair with nerve transfer and suggest that efforts to improve the results from nerve repair should address the peripheral nerve as well as the brain. © 2010 Wiley‐Liss, Inc. Microsurgery 2010.     

成年大鼠全臂丛根性撕脱伤后对侧运动皮层可塑性变化的实验研究

目的 探讨成年大鼠全臂丛根性撕脱伤后不同时间段对侧运动皮层的可塑性变化。方法 将30只SD雄性大鼠分为6组，即正常对照组和全臂丛根性撕脱伤术后1d、7d、1个月、3个月、1年共5个时间组，每组5只。采用皮层内微电极电刺激技术，定量评价大鼠左前肢代表区内的可塑性变化。结果 术后不同时间组在原前肢代表区内可诱发出不同的运动类型，包括左侧胡须、下颌、颈部和左下肢4个部位点的运动，但只有颈部位点自始至终占据着术前前肢代表区。结论 成年大鼠的运动皮层仍具有可塑性，术后对侧运动皮层在术前前肢代表区发生了功能重组，并且这种功能重组是动态变化的。瘫痪肢体以上最临近部位的肌肉控制力其代偿性明显增强。     

Increased regional cerebral blood flow in the contralateral thalamus after successful motor cortex stimulation in a patient with poststroke pain

The mechanisms underlying poststroke pain have not been clearly identified. Although motor cortex stimulation (MCS) sometimes reduces poststroke pain successfully, the exact mechanism is not yet known. For further investigation of the neural pathways involved in the processing of poststroke pain and in pain reduction by MCS, the authors used positron emission tomography (PET) scanning to determine significant changes in regional cerebral blood flow (rCBF). This 58-year-old right-handed man suffered from right-sided poststroke pain for which he underwent implantation of a stimulation electrode in the right motor cortex. After 30 minutes of stimulation, his pain was remarkably reduced (Visual Analog Scale scores decreased 8 to 1) and he felt warmth in his left arm. The rCBF was studied using PET scanning with 15O-labeled water when the patient was in the following states: before MCS (painful condition, no stimulation) and after successful MCS (painless condition, no stimulation). The images were analyzed using statistical parametric mapping software. State-dependent differences in global blood flow were covaried using analysis of covariance. Comparisons of the patient's rCBF in the painful condition with that in the painless condition revealed significant rCBF increases in the left rectus gyrus (BA11), left superior frontal lobe (BA9), left anterior cingulate gyms (BA32), and the left thalamus (p < 0.05, corrected). On the other hand, there were significant decreases in rCBF in the right superior temporal gyrus (BA22, p < 0.01, corrected) and the left middle occipital gyrus (BA19, p < 0.05, corrected). The efficacy of MCS was mainly related to increased synaptic activity in the thalamus, whereas the activations in the rectus gyrus, anterior cingulate gyrus, and superior frontal cortex as well as the inactivation of the superior temporal lobe may be related to emotional processes. This is the first report in which the contralateral thalamus was significantly activated and pain relief was achieved using MCS.     

Seeing touch is correlated with content-specific activity in primary somatosensory cortex

There is increasing evidence to suggest that primary sensory cortices can become active in the absence of external stimulation in their respective modalities. This occurs, for example, when stimuli processed via one sensory modality imply features characteristic of a different modality; for instance, visual stimuli that imply touch have been observed to activate the primary somatosensory cortex (SI). In the present study, we addressed the question of whether such cross-modal activations are content specific. To this end, we investigated neural activity in the primary somatosensory cortex of subjects who observed human hands engaged in the haptic exploration of different everyday objects. Using multivariate pattern analysis of functional magnetic resonance imaging data, we were able to predict, based exclusively on the activity pattern in SI, which of several objects a subject saw being explored. Along with previous studies that found similar evidence for other modalities, our results suggest that primary sensory cortices represent information relevant for their modality even when this information enters the brain via a different sensory system.     

Spatial attention modulates initial afferent activity in human primary visual cortex

It is well established that spatially directed attention enhances visual perceptual processing. However, the earliest level at which processing can be affected remains unknown. To date, there has been no report of modulation of the earliest visual event-related potential component "C1" in humans, which indexes initial afference in primary visual cortex (V1). Thus it has been suggested that initial V1 activity is impenetrable, and that the earliest modulations occur in extrastriate cortex. However, the C1 is highly variable across individuals, to the extent that uniform measurement across a group may poorly reflect the dynamics of V1 activity. In the present study we employed an individualized mapping procedure to control for such variability. Parameters for optimal C1 measurement were determined in an independent, preliminary "probe" session and later applied in a follow-up session involving a spatial cueing task. In the spatial task, subjects were cued on each trial to direct attention toward 1 of 2 locations in anticipation of an imperative Gabor stimulus and were required to detect a region of lower luminance appearing within the Gabor pattern 30% of the time at the cued location only. Our data show robust spatial attentional enhancement of the C1, beginning as early as its point of onset (57 ms). Source analysis of the attentional modulations points to generation in striate cortex. This finding demonstrates that at the very moment that visual information first arrives in cortex, it is already being shaped by the brain's attentional biases.     

Organization of nonprimary motor cortical inputs on pyramidal and nonpyramidal tract neurons of primary motor cortex: An electrophysiological study in the macaque monkey

To elucidate the functions of nonprimary motor cortical (nPMC) areas whose afferents synapse onto output neurons of the primary motor cortex (PMC), we examined the responses of pyramidal tract neurons (PTNs) and non-PTNs (nPTNs) to electrical stimulation in the three nPMCs, the supplementary motor area (SMA) and the dorsal and ventral divisions of the premotor cortex (PMd and PMv), with extracellular unit recording in alert monkeys. Typical responses of PTNs to nPMC stimulation were early orthodromic excitatory responses followed by inhibitory responses. Among 27 PTNs tested by constructing peri-stimulus time histograms, 19 (70.4%) showed inhibitory responses to stimulation in all of the nPMC areas. In contrast, 5/33 PTNs (15.2%) and 10/72 nPTNs (13.9%) showed excitatory responses to stimulation in all of the nPMCs. The inhibitory responses of PTNs were mediated by inhibitory interneurons, some of which may correspond to nPTNs in the superficial layers of the PMC. These interneurons probably possess widely extended axons and nonspecifically inhibit multiple PTNs in layer V. The excitatory and inhibitory influences, and the patterns of convergence of inputs from the nPMCs onto the PTNs, are important to understand motor control by the nPMC-PMC-spinal cord pathway.     

Maintaining force control despite changes in emotional context engages dorsomedial prefrontal and premotor cortex

Viewing emotional as compared with neutral images results in an increase in force production. An emotion-driven increase in force production has been associated with increased brain activity in ventrolateral prefrontal cortex and primary motor cortex (M1). In many instances, however, force production must be held constant despite changes in emotional state and the neural circuits underlying this form of control are not well understood. To address this issue, we designed a task in which subjects viewed pleasant, unpleasant, and neutral images during a force production task. We measured brain activity using functional magnetic resonance imaging and examined functional connectivity between emotion and motor circuits. Despite similar force performance across conditions, increased brain activity was evidenced in dorsomedial prefrontal cortex (dmPFC) and left ventral premotor cortex (PMv) when force was produced during emotional as compared with neutral conditions. Connectivity analyses extended these findings by demonstrating a task-dependent functional circuit between dmPFC and ventral and dorsal portions of premotor cortex. Our findings show that when force production has to be consistent despite changes in emotional context, a functional circuit between dmPFC and PMv and dorsal premotor cortex is engaged.     

Role of the ipsilateral primary motor cortex in controlling the timing of hand muscle recruitment

The precise contribution of the ipsilateral primary motor cortex (iM1) to hand movements remains controversial. To address this issue, we elicited transient virtual lesions of iM1 by means of transcranial magnetic stimulation (TMS) in healthy subjects performing either a grip-lift task or a step-tracking task with their right dominant hand. We found that, irrespective of the task, a virtual lesion of iM1 altered the timing of the muscle recruitment. In the grip-lift task, this led to a less coordinated sequence of grip and lift movements and in the step-tracking task, to a perturbation of the movement trajectory. In the step-tracking task, we have demonstrated that disrupting iM1 activity may, depending on the TMS delay, either advance or delay the muscle recruitment. The present study suggests that iM1 plays a critical role in hand movements by contributing to the setting of the muscle recruitment timing, most likely through either inhibitory or facilitatory transcallosal influences onto the contralateral M1 (cM1). iM1 would therefore contribute to shape precisely the muscular command originating from cM1.     

Higher incidence of epilepsy in meningiomas located on the premotor cortex: a voxel-wise statistical analysis

Background

A substantial number of patients with brain tumors develop recurrent seizures, known as tumor-associated epilepsy. It is important to identify specific subgroups of brain tumor patients with higher incidences of epilepsy because a meta-analysis failed to certify the effectiveness of prophylactic anti-epileptic drugs (AEDs) to abort tumor-associated epilepsy as a whole.

Methods

To investigate the relationship between tumor location and incidence of epilepsy, we performed voxel-wise comparison between 3D MRI scans obtained from patients with meningioma-associated epilepsy and those from control patients using spatial normalization techniques on neuroimaging data. Variables such as age, tumor size, the degree of edema, and pathological diagnosis were also compared between the two groups.

Results

Our results showed the highest incidence of epilepsy when the tumor was located on the premotor cortex in the frontal lobe (Z-scores >2.0, Liebermeister’s quasi-exact test). The stepwise multiple regression analysis on the clinical data revealed that the tumor diameter (p?<?0.001) and the patient’s age (p?=?0.024) were positive and negative predictors, respectively, for the onset of epilepsy.

Conclusions

The incidence of epilepsy was higher in meningiomas located on the premotor cortex than on the other cortex. Larger volume also contributed to the onset of epilepsy. We suggest that variations of epilepsy incidence dependent on tumor characteristics can be considered when treating tumor-associated epilepsy.     

Differences in the corticospinal projection from primary motor cortex and supplementary motor area to macaque upper limb motoneurons: an anatomical and electrophysiological study

To further our understanding of the functional roles of different motor cortical areas, we made a quantitative comparison of the density of corticospinal projections from primary motor cortex (M1) and supplementary motor area (SMA) to spinal motor nuclei supplying hand and finger muscles in four macaque monkeys. We also compared the action of corticospinal outputs excited by electrical stimulation of these two areas on upper limb motoneurons recorded in three anaesthetized macaques. The hand representations of SMA and M1 were first identified using structural magnetic resonance imaging scans and intracortical microstimulation. In the anatomical study we then made focal injections of wheatgerm agglutinin- horseradish peroxidase into these representations, which were subsequently confirmed by analysis of retrograde cortical labelling. Densitometric analysis showed that corticospinal projections from M1 were denser and occupied a greater proportion of the hand muscle motor nuclei than did projections from SMA. In caudal Th1 the densest projections from M1 occupied 81% of this motoneuronal area, compared with only 6% from SMA. In the electrophysiological study, bipolar intracortical stimulation of the hand representation of M1 and SMA evoked direct (D) and indirect (I) corticospinal volleys. Volleys elicited by M1 stimulation had larger amplitudes and faster conduction velocities than those evoked from the SMA. Intracellular recordings were made from 84 contralateral upper limb motoneurons. M1 and SMA stimulation evoked markedly different responses in tested motoneurons: EPSPs were larger and more common from M1 (88% of motoneurons) than from SMA (48%). Some motoneurons (16/84) showed evidence of excitatory postsynaptic potentials mediated by monosynaptic action of the D-wave evoked from M1; these early effects were not observed from the SMA. In most motoneurons (74/84) EPSPs had segmental latencies indicating that they were due to monosynaptic action of the I-wave. The results are consistent with cortico-motoneuronal (CM) connections originating from both SMA and M1 converging upon single motoneurons, but those from M1 are far more numerous and exert stronger excitatory effects than from the SMA. Thus although they may function in parallel, the two CM projections probably make different contributions to upper limb motor control.