Chronic administration of selective serotonin reuptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects

The aim of the study was to investigate the effect of chronic administration of paroxetine (selective serotonin reuptake inhibitor: SSRI) on motor cortex excitability in healthy subjects by means of transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) and behavioral motor tests. In a randomized, double-blind, crossover study, twenty-one right-handed subjects received 20 mg daily of either paroxetine or a placebo over a period of 30 days separated by a period of 3 months wash-out. The TMS study is presented here correlated with some results of the motor behavior study (finger tapping test) and the fMRI study (primary sensorimotor cortex (S1M1) volume of activation). TMS was used to test motor threshold (MT), motor evoked potential recruitment curve (RC), cortical silent period (CSP) and paired-pulse intracortical inhibition and facilitation (ICI, ICF). Chronic administration of paroxetine did not modulate ICI or CSP but induced a significant enhancement of mean ICF (ANOVA P=0.04), which significantly correlated with increase of speed in a finger tapping test (P=0.02). This suggests a modulation of cortical interneuronal excitatory pathways without changes in the excitability of cortical inhibitory GABAergic interneurons. A decrease of RC (ANOVA P=0.05) was also observed after 30 days intake of paroxetine in comparison with placebo and was associated with changes of fMRI activation intensity (left S1M1 hypoactivation, ), without changes of S1M1 activation volume. Finally, the different modulation of RC and ICF after chronic administration of paroxetine compared to single dose (opposite effects) emphasizes the different pharmacological action of the drug at cortical level depending on its acute or long-term administration.     

Alteration of cortical excitability in patients with fibromyalgia

We assessed cortical excitability and intracortical modulation systematically, by transcranial magnetic stimulation (TMS) of the motor cortex, in patients with fibromyalgia. In total 46 female patients with fibromyalgia and 21 normal female subjects, matched for age, were included in this study. TMS was applied to the hand motor area of both hemispheres and motor evoked potentials (MEPs) were recorded for the first interosseous muscle of the contralateral hand. Single-pulse stimulation was used for measurements of the rest motor threshold (RMT) and suprathreshold MEP. Paired-pulse stimulation was used to assess short intracortical inhibition (SICI) and intracortical facilitation (ICF). Putative correlations were sought between changes in electrophysiological parameters and major clinical features of fibromyalgia, such as pain, fatigue, anxiety, depression and catastrophizing. The RMT on both sides was significantly increased in patients with fibromyalgia and suprathreshold MEP was significantly decreased bilaterally. However, these alterations, suggesting a global decrease in corticospinal excitability, were not correlated with clinical features. Patients with fibromyalgia also had lower ICF and SICI on both sides, than controls, these lower values being correlated with fatigue, catastrophizing and depression. These neurophysiological alterations were not linked to medication, as similar changes were observed in patients with or without psychotropic treatment. In conclusion, fibromyalgia is associated with deficits in intracortical modulation involving both GABAergic and glutamatergic mechanisms, possibly related to certain aspects of the pathophysiology of this chronic pain syndrome. Our data add to the growing body of evidence for objective and quantifiable changes in brain function in fibromyalgia.     

功能性核磁共振成像在计算机辅助的上肢功能训练治疗脑梗死上肢偏瘫中的应用研究

目的:探讨计算机辅助训练上肢对脑可塑性的可能作用。方法:脑卒中上肢偏瘫患者10例,均进行计算机辅助训练,治疗前后采用偏瘫上肢功能测试-香港版(FTHUE-HK),Fulg-Meyer上肢评定(FMA)及改良Barthel指数量表(MBI)评定上肢运动功能,及患者屈伸腕关节时进行功能核磁共振扫描(fMRI)。结果:治疗6周后,10例患侧的上肢功能评定FTHUE-HK、FMA及MBI评分均较治疗前后患侧上肢功能评定变化明显提高(P0.05)。fMRI扫描示:患者健侧手运动脑功能激活区主要位于对侧初级运动皮质区(SMC)及同侧小脑,患者健手在康复训练后脑激活区增多,包括对侧SMC区及同侧小脑、部分边缘系统;患者治疗前患侧手运动激活区分布广泛,而对侧SMC激活减少,同侧SMC激活增多,另主要还见辅助运动区激活增多;治疗后可见双侧SMC及辅助运动区激活,对侧SMC激活较治疗前增多,另主要还见对侧顶上小叶激活增多。结论:计算机训练可以有效改善脑卒中患者上肢运动功能,诱发大脑皮质功能重塑是其机制的重要组成部分。     

卒中早期手指被动运动的脑功能磁共振成像研究

目的应用扩散张量成像及BOLD-fMRI技术观察卒中早期手指被动运动时大脑半球相关区域血氧水平的变化情况.方法采用1.5 T MR成像系统对6名早期卒中患者进行BOLD-fMRI及扩散张量成像,采用手指被动屈伸运动作为fMRI的刺激任务.结果在锥体束中断时,卒中早期健手运动时激活双侧SMC区,患手运动可激活对侧半球后顶叶皮层及同侧SMC区;锥体束较完整时健手运动时激活对侧SMC区,患手运动激活双侧SMC区、双侧后顶叶皮层.结论卒中早期可能发生运动功能通路的重构,但锥体束不同损伤情况下运动功能恢复可能存在不同的机制.DTI与fMRI联合应用将是监测和研究脑卒中后恢复的有用工具.     

Reduction of excitability ("inhibition") in the ipsilateral primary motor cortex is mirrored by fMRI signal decreases

Functional magnetic resonance imaging (fMRI) was used to investigate how focal cortical inhibition affects the blood oxygen level-dependent (BOLD) signal. Phasic low force pinch grip reduces excitability of the ipsilateral primary motor cortex. This task was used to study BOLD signal changes during inhibition. Six right-handed normal volunteers participated in the study. They were asked to perform a right-handed pinch grip repetitively at 1 Hz and 5% of their individual maximal voluntary contraction (MVC). Data were acquired with a 1.5 Tesla Magnetom and continuous multislice T2*-weighted images. The contralateral primary motor cortex (M1) revealed an activation in the knob-shaped hand representation of the central sulcus area. More importantly, a decreased (often referred to as "negative") BOLD signal in the ipsilateral M1 was observed. We suggest phasic low force pinch grip as a reproducible, easy model of focal inhibition. Decreased cortical excitability presents as decreased BOLD signal using fMRI.     

Integrated technology for evaluation of brain function and neural plasticity

The study of neural plasticity has expanded rapidly in the past decades and has shown the remarkable ability of the developing, adult, and aging brain to be shaped by environmental inputs in health and after a lesion. Robust experimental evidence supports the hypothesis that neuronal aggregates adjacent to a lesion in the sensorimotor brain areas can take over progressively the function previously played by the damaged neurons. It definitely is accepted that such a reorganization modifies sensibly the interhemispheric differences in somatotopic organization of the sensorimotor cortices. This reorganization largely subtends clinical recovery of motor performances and sensorimotor integration after a stroke. Brain functional imaging studies show that recovery from hemiplegic strokes is associated with a marked reorganization of the activation patterns of specific brain structures. To regain hand motor control, the recovery process tends over time to bring the bilateral motor network activation toward a more normal intensity/extent, while overrecruiting simultaneously new areas, perhaps to sustain this process. Considerable intersubject variability exists in activation/hyperactivation pattern changes over time. Some patients display late-appearing dorsolateral prefrontal cortex activation, suggesting the development of "executive" strategies to compensate for the lost function. The AH in stroke often undergoes a significant "remodeling" of sensory and motor hand somatotopy outside the "normal" areas, or enlargement of the hand representation. The UH also undergoes reorganization, although to a lesser degree. Although absolute values of the investigated parameters fluctuate across subjects, secondary to individual anatomic variability, variation is minimal with regards to interhemispheric differences, due to the fact that individual morphometric characters are mirrored in the two hemispheres. Excessive interhemispheric asymmetry of the sensorimotor hand areas seems to be the parameter with highest sensitivity in describing brain reorganization after a monohemispheric lesion, and mapping motor and somatosensory cortical areas through focal TMS, fMRI, PET, EEG, and MEG is useful in studying hand representation and interhemispheric asymmetries in normal and pathologic conditions. TMS and MEG allow the detection of sensorimotor areas reshaping, as a result of either neuronal reorganization or recovery of the previously damaged neural network. These techniques have the advantage of high temporal resolution but also have limitations. TMS provides only bidimensional scalp maps, whereas MEG, even if giving three-dimensional mapping of generator sources, does so by means of inverse procedures that rely on the choice of a mathematical model of the head and the sources. These techniques do not test movement execution and sensorimotor integration as used in everyday life. fMRI and PET may provide the ideal means to integrate the findings obtained with the other two techniques. This multitechnology combined approach is at present the best way to test the presence and amount of plasticity phenomena underlying partial or total recovery of several functions, sensorimotor above all. Dynamic patterns of recovery are emerging progressively from the relevant literature. Enhanced recruitment of the affected cortex, be it spared perilesional tissue, as in the case of cortical stroke, or intact but deafferented cortex, as in subcortical strokes, seems to be the rule, a mechanism especially important in early postinsult stages. The transfer over time of preferential activation toward contralesional cortices, as observed in some cases, seems, however, to reflect a less efficient type of plastic reorganization, with some aspects of maladaptive plasticity. Reinforcing the use of the affected side can cause activation to increase again in the affected side with a corresponding enhancement of clinical function. Activation of the UH MI may represent recruitment of direct (uncrossed) corticospinal tracts and relate more to mirror movements, but it more likely reflects activity redistribution within preexisting bilateral, large-scale motor networks. Finally, activation of areas not normally engaged in the dysfunctional tasks, such as the dorsolateral prefrontal cortex or the superior parietal cortex in motor paralysis, might reflect the implication of compensatory cognitive strategies. An integrated approach with technologies able to investigate functional brain imaging is of considerable value in providing information on the excitability, extension, localization, and functional hierarchy of cortical brain areas. Deepening knowledge of the mechanisms regulating the long-term recovery (even if partial), observed for most neurologic sequelae after neural damage, might prompt newer and more efficacious therapeutic and rehabilitative strategies for neurologic diseases.     

Combined functional magnetic resonance imaging and transcranial magnetic stimulation evidence of ipsilateral motor pathway with congenital brain disorder: A case report

We present the case of 28-year-old man with schizencephaly who had mild left hemiparesis with mirror movement. Brain mapping using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) for both hand muscles was done to evaluate his neurologic state. Motor evoked potential (MEP) from both abductor pollicis brevis (APB) muscles was obtained simultaneously. fMRI showed that the left primary sensorimotor cortex became active when the right fingers performed the flexion-extension exercise. The left primary sensorimotor cortex, left prefrontal area, and both supplementary motor areas were activated with flexion-extension exercise of the left hand. Brain mapping for both APB muscles using TMS showed that no MEP was evoked in the right hemisphere, but a APB total of 5 sites were evoked in the left hemisphere simultaneously. The optimal scalp site for both APB muscles was present at the same site. The MEPs of both muscles which were evoked by stimulation of the optimal scalp site, showed similar latencies, amplitudes, and figures of potential. The similarities in both MEPs and the same optimal scalp site support the assumption that MEPs of both APB muscles are produced by the corticospinal tract originating from the same motor cortex. Our results showed that the ipsilateral motor pathway extended from the unaffected left hemisphere to both hand muscles. This finding may reflect functional reorganization of motor area in a patient with congenital brain disorder.     

运动想象训练促进脑卒中患者上肢运动功能恢复的功能磁共振研究

摘要 目的：利用功能磁共振（fMRI）研究脑卒中患者运动想象训练后上肢功能重组潜在的脑重塑机制,为临床脑卒中患者的康复治疗提供一定的理论基础。 方法：选择9例脑卒中偏瘫患者,进行运动想象训练每周5次,每次约30min,共4周,并进行常规康复训练。应用Fugl-Meyer上肢运动功能量表（FMA-UL）分别在治疗前和治疗后4周评估患者的上肢运动功能。在4周康复干预前后对患者进行患手被动握拳任务下的fMRI检查,采用组块设计,利用SPM8软件进行数据处理,采用感兴趣区（ROI）的个体化分析,统计各ROI区的脑皮质激活情况,比较干预前后对侧感觉运动区（cSMC）的激活变化,分析脑卒中患者的脑重塑模式。 结果：4周运动想象干预后脑卒中患者的FM-UL评分从（22.44±11.59）分提高到（39.78±14.03）分（P=0.011）。比较干预前后两次fMRI检查脑皮质SMC区的激活情况,发现9例脑卒中患者的功能恢复呈现出两种不同的皮质重塑模式：一种模式为募集激活,即大部分患者第二次fMRI检查,患手被动任务下cSMC的激活增加（有6例患者）;另一种模式是集中激活,即小部分患者第二次fMRI检查,患手被动任务下cSMC的激活虽然是减少的,但其偏侧指数（LI-SMC）却是显著增加的（有3例患者）。 结论：运动想象训练可改善脑卒中患者的上肢运动功能,经过4周干预后脑卒中患者存在损伤同侧SMC区的募集激活和集中激活两种脑重塑模式,随着患者上肢功能的恢复,脑重塑机制逐渐倾向于损伤侧SMC的激活。     

运动想象治疗脑卒中患者手部运动功能的功能磁共振研究

目的：探讨运动想象（MI）治疗对脑卒中后脑功能重塑的影响。方法：将16例脑卒中患者随机分为运动想象组（MI）6例、执行运动（EM）组5例、对照组（CG）5例。3组在常规康复治疗基础上,MI组、EM组分别进行运动想象、实际动作治疗,每次30min,每周5次,为期4周。治疗前、后进行运动功能评价,并使用功能磁共振（fMRI）观察患手对指实际动作、想象时偏瘫对侧感觉运动区的激活情况,定量分析治疗前后cSMC区的激活强度t、LI变化。结果：治疗4周后,MI组及EM组FMA、STEF评分较前均有明显提高（均P＜0.05）,且MI组上述评分均更高于其它2组（均P＜0.05）。治疗后,3组MBI评分均有提高,但组内及组间差异无统计学意义。运动想象与运动执行的激活部位相似：治疗前运动想象激活区主要位于双侧SMC区、双侧SMA区,治疗后,各组双侧SMC区激活强度有增大趋势,MI组对侧SMC区激活显著（P＜0.05）,且对侧偏侧化优势较CG组显著（P＜0.05）。结论：运动想象治疗能够明显改善脑卒中后患者手功能,其机制可能与运动想象促进脑功能重塑有关。     

Muscle pain differentially modulates short interval intracortical inhibition and intracortical facilitation in primary motor cortex

Excitability of the motor cortex can be suppressed during muscle pain. Yet the mechanisms are largely unknown. Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were examined as possible candidate mechanisms to underpin this change. SICI and ICF were investigated in 11 healthy individuals before, during and after infusion of hypertonic saline into right first dorsal interosseous (FDI). Using paired-pulse transcranial magnetic stimulation (TMS), interstimulus intervals of 2, 3, and 13 ms were investigated. Pain intensity and quality were recorded using a 10-cm visual analogue scale and the McGill Pain Questionnaire. Resting motor threshold and motor-evoked potentials (MEPs) to single TMS stimuli were recorded before and after pain. Electromyographic recordings were made from right FDI and abductor digiti minimi. Participants reported an average pain intensity of 5.8 (1.6) cm. MEP amplitudes decreased in both muscles. Compared with the pre-pain condition, SICI was increased following pain, but not during. ICF was decreased both during and after pain when compared with the pre-pain condition. These findings suggest that muscle pain differentially modulates SICI and ICF. Although the functional relevance is unknown, we hypothesize decreased facilitation and increased inhibition may contribute to the restriction of movement of a painful body part.PerspectiveThis article provides evidence for decreased intracortical facilitation and increased short interval intracortical inhibition in response to muscle pain. This finding is relevant to clinicians as a mechanism which may underlie restricted movement in acute and chronic pain.     

计算机辅助上肢训练对脑卒中患者与正常人脑可塑性影响的功能磁共振成像对比研究

摘要 目的：探讨计算机辅助训练上肢对脑卒中患者与正常人脑可塑性的可能作用。 方法：对5名正常志愿者（对照组）及5例脑卒中上肢偏瘫患者（实验组）进行6周的计算机辅助训练,每周训练5次,在训练前、训练后分别在受试者屈伸左右腕关节时进行功能磁共振成像（fMRI）扫描,并对实验组进行Fulg-Meyer上肢功能评定（FMA）,改良Barthel指数（MBI）量表评定。 结果：实验组与对照组相比,治疗前,运动左侧腕关节时,激活脑区主要在左额中央前回（同侧的感觉运动皮质区）;治疗后,运动左侧腕关节时,实验组与对照组相比,激活脑区在同侧感觉运动皮质区,但激活强度及体素均较治疗前有明显的降低。治疗前,运动右腕关节时,两者的激活脑区的部位相似,均在对侧的SMC区及同侧的小脑,但激活强度和体素较对照组小;治疗后,运动右腕关节时,两组之间无显著差异。 结论：计算机辅助训练可诱导出大脑皮质功能区的重组与代偿,使其趋向正常化。     

脑缺血性卒中患者运动功能康复的功能性磁共振成像研究

目的利用功能性磁共振成像（fMRI）技术研究急性期缺血性脑卒中患者（以下简称急性期患者）运动相关皮质的激活情况，并探讨脑卒中后脑功能重组特点及其与肢体运动功能恢复的关系。方法采用GEI．5T双梯度16通道磁共振成像系统，对9例急性期患者和9例健康志愿者行Bold—fMRI检查。fMRI检查以被动对指运动（以下简称运动）为刺激任务，所有数据采用SPM2软件包进行离线后处理。比较健康志愿者与急性期患者fMRI结果的异同点，计算脑激活区体积和单侧化指数（LI），考察急性期患者患手运动LI值与患手运动功能的关系。结果健康志愿者单手运动激活对侧感觉运动皮质（SMC）、双侧辅助运动区（SMA）。急性期患者患手运动时同侧半球脑激话增多，健手运动的fMRI结果与健康志愿者基本一致。LI值也进一步确定，急性期患者患手运动时同侧半球脑激活增多。统计学分析表明，急性期患者患手运动的LI值与患手运动功能呈正相关。结论fMRI检查能客观地反映急性期患者运动相关皮质改变，提示存在脑功能代偿与重组。急性期患者患手运动LI值与患手运动功能呈正相关，提示fMRI是研究缺血性脑卒中后肢体运动功能康复与脑功能重组之间关系的一种有效工具。     

Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients

We studied motor representation in well-recovered stroke patients. Eighteen right-handed stroke patients and eleven age-matched control subjects underwent functional Magnetic Resonance Imaging (fMRI) while performing unimanual index finger (abduction-adduction) and wrist movements (flexion-extension) using their recovered and non-affected hand. A subset of these patients underwent Transcranial Magnetic Stimulation (TMS) to elicit motor evoked potentials (MEP) in the first dorsal interosseous muscle of both hands. Imaging results suggest that good recovery utilizes both ipsi- and contralesional resources, although results differ for wrist and index finger movements. Wrist movements of the recovered arm resulted in significantly greater activation of the contralateral (lesional) and ipsilateral (contralesional) primary sensorimotor cortex (SM1), while comparing patients to control subjects performing the same task. In contrast, recovered index finger movements recruited a larger motor network, including the contralateral SM1, Supplementary Motor Area (SMA) and cerebellum when patients were compared to control subjects. TMS of the lesional hemisphere but not of the contralesional hemisphere induced MEPs in the recovered hand. TMS parameters also revealed greater transcallosal inhibition, from the contralesional to the lesional hemisphere than in the reverse direction. Disinhibition of the contralesional hemisphere observed in a subgroup of our patients suggests persistent alterations in intracortical and transcallosal (interhemispheric) interactions, despite complete functional recovery.     

Short-term modulation of regional excitability and blood flow in human motor cortex following rapid-rate transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) of the human primary motor cortex (M1) provides a means of inducing lasting changes in cortical excitability and synaptic activity. Here we combined rTMS with positron emission tomography of regional cerebral blood flow (rCBF) to examine how an rTMS-induced change in intracortical excitability of inhibitory circuits affects regional synaptic activity. In a first set of experiments, we gave 150 biphasic pulses of 5 Hz rTMS at 90% of active motor threshold to left M1 and used single- and paired-pulse TMS to assess the conditioning effects of rTMS on motor cortical excitability at rest. rTMS conditioning led to a selective decrease in short-latency intracortical inhibition (SICI) without affecting short-latency intracortical facilitation or corticospinal excitability. The decrease in SICI lasted for approximately 8 min. In a second experiment, we used the same rTMS protocol and measured changes in regional synaptic activity (as indexed by rCBF) during and for up to 14 min after the end of rTMS. Subthreshold 5 Hz rTMS induced a region-specific increase in resting rCBF in the stimulated M1 lasting approximately 8 min. These results suggest that in the stimulated M1, temporary attenuation of SICI is paralleled by an increase in synaptic activity, consistent with reduced efficacy of intracortical GABA(A)-ergic synapses. The present findings demonstrate that short trains of low-intensity 5 Hz rTMS can be used to induce a transient change in function within a distinct cortical area. This opens up new possibilities for studying acute reorganization at the systems level in the intact human brain.     

Structural damage to the corticospinal tract correlates with bilateral sensorimotor cortex reorganization in stroke patients

Damage to the corticospinal tract (CST) in stroke patients has been associated with functional reorganization in the ipsilesional and contralesional sensorimotor cortices. However, it is unknown whether a quantitative relationship exists between the extent of structural damage to the CST and functional reorganization in stroke patients. The purpose of the current study was to examine the relationship between structural CST damage and motor task-related cortical activity in chronic hemiparetic stroke patients. In 10 chronic hemiparetic stroke patients with heterogeneous lesions, CST damage was quantified using conventional structural magnetic resonance imaging and tractography based on diffusion tensor imaging. Cortical activity was measured using functional magnetic resonance imaging during repetitive flexion/extension movements of the digits. We found that the two measures of CST damage were strongly correlated. Moreover, greater CST damage was significantly and linearly correlated with increased activation during affected hand movement in the hand area of the contralesional primary sensorimotor cortex (M1/S1) and in the ipsilesional M1/S1 ventral to the hand area. To our knowledge, this is the first demonstration of a quantitative relationship between the extent of structural damage to the CST and functional reorganization in stroke patients. This relationship was observed in stroke patients with heterogeneous lesions, suggesting that CST damage is a factor relevant to the variation in functional reorganization in the clinical population.     

Cortical reorganization of hand motor function to primary sensory cortex in hemiparetic patients with a primary motor cortex infarct

OBJECTIVE: To show cortical reorganization in hemiparetic patients with a primary motor cortex (M1) infarct including the precentral knob by using functional magnetic resonance imaging (fMRI). DESIGN: Case-control. SETTING: Outpatient clinics in the rehabilitation department of a university hospital. PARTICIPANTS: Two stroke patients and 20 control subjects. INTERVENTIONS: By using fMRI, we evaluated the hand motor function of 2 hemiparetic stroke patients, who had made some recovery from complete paralysis of the affected hand, and 20 control subjects. MAIN OUTCOME MEASURES: fMRI was performed by using the blood oxygen level-dependent technique at 1.5 T with a standard head coil. The motor task paradigm consisted of hand grasp-release movements. RESULTS: The contralateral primary sensorimotor cortex was activated by the hand movements of the control subjects and of the unaffected side of the 2 patients. Only the contralateral (infarct side) primary sensory cortex (S1) was activated by the movements of the affected hand of the 2 patients, a result that was not observed in the control subjects or with the unaffected hand in the stroke patients. CONCLUSIONS: The hand motor function associated with the infarcted M1 in our patients was reorganized into the S1. These results suggest cortical reorganization in patients with an M1 infarct.     

Correlation between cerebral reorganization and motor recovery after subcortical infarcts

Our objective was to investigate correlations between clinical motor scores and cerebral sensorimotor activation to demonstrate that this reorganization is the neural substratum of motor recovery. Correlation analyses identified reorganization processes shared by all patients. Nine patients with first-time corticospinal tract lacuna were clinically evaluated using the NIH stroke scale, the motricity index, and the Barthel index. Patients were strictly selected for pure motor deficits. They underwent a first fMRI session (E1) 11 days after stroke, and then a second (E2) 4 weeks later. The task used was a calibrated repetitive passive flexion/extension of the paretic wrist. The control task was rest. Six healthy subjects followed the same protocol. Patients were also clinically evaluated 4 and 12 months after stroke. All patients improved significantly between E1 and E2. For E1 and E2, the ipsilesional primary sensorimotor and premotor cortex, supplementary motor area (SMA), and bilateral Broadmann area (BA) 40 were activated. Activation intensity was greater at the second examination except in the ipsilesional superior BA 40. Magnitude of activation was lower than that of controls except for well-recovered patients. E1 clinical hand motor score and E1 cerebral activation correlated in the SMA proper and inferior ipsilesional BA 40. Thus, we demonstrated early functionality of the sensorimotor system. The whole sensorimotor network activation correlated with motor status at E2, indicating a recovery of its function when activated. Moreover, the activation pattern in the acute phase (E1) had a predictive value: early recruitment and high activation of the SMA and inferior BA 40 were correlated with a faster or better motor recovery. On the contrary, activation of the contralesional hemisphere (prefrontal cortex and BA 39-40) and of the posterior cingulate/precuneus (BA 7-31) predicted a slower recovery.     

Ipsilateral motor pathway confirmed by combined brain mapping of a patient with hemiparetic stroke: a case report

This study investigated the motor control pathway using both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in a patient with left hemiparesis with an infarction on the posterior limb of the right internal capsule. fMRI was performed using the blood oxygen level-dependent technique at 1.5 T with a standard head coil. The motor activation task consisted of hand grasp-release movements in 1-Hz cycles. TMS was performed using a butterfly coil; the intersection of the wings (center of the coil) was applied tangentially to the scalp 1.0 cm apart. Stimulation was performed at 100% of maximal output. Motor evoked potentials (MEPs) from both abductor pollicis brevis (APB) muscles were obtained simultaneously. fMRI showed that the unaffected (left) primary sensorimotor cortex (SM1) was activated by movements of the unaffected (right) hand. Conversely, the bilateral SM1 were activated by movements of the affected (left) hand. Brain mapping using TMS showed that ipsilateral MEPs were obtained at the affected (left) APB muscle when the unaffected (left) motor cortex was stimulated. We concluded that the ipsilateral motor pathway from the unaffected motor cortex to the affected hand was present in this patient.     

Unilateral Strength Training of the Less Affected Hand Improves Cortical Excitability and Clinical Outcomes in Patients With Subacute Stroke: A Randomized Controlled Trial

ObjectivesTo investigate whether unilateral strength training helps improve cortical excitability and clinical outcomes after stroke.DesignRandomized controlled trial.SettingRehabilitation sciences research center.ParticipantsPatients with subacute stroke (N=26) were randomly assigned to a control group (n=13) or the experimental group (n=13).InterventionsParticipants in both groups received conventional physiotherapy. The experimental group also received unilateral strength training of the less affected wrist extensors. Interventions were applied for 4 weeks (12 sessions, 3 d/wk).Main Outcome MeasuresCortical excitability in both the ipsilesional hemisphere (ipsiH) and contralesional hemisphere (contraH) was assessed by measuring resting motor threshold (RMT), active motor threshold (AMT), motor evoked potential (MEP), and cortical silent period (CSP) at baseline and after the 4-week intervention period. Clinical outcomes were obtained by evaluating wrist extension strength in both the more affected and less affected hands, upper extremity motor function, activities of daily living (ADL), and spasticity.ResultsThe experimental group showed greater MEP amplitude (P=.001) in the ipsiH and shorter CSP duration in both the ipsiH (P=.042) and contraH (P=.038) compared with the control group. However, the reductions in RMT and AMT in both hemispheres were not significantly different between groups. Improvements in wrist extension strength in the more affected (P=.029) and less affected (P=.001) hand, upper extremity motor function (P=.04), and spasticity (P=.014) were greater in the experimental group. No significant difference in ADLs was detected between groups.ConclusionsA combination of unilateral strength training and conventional physiotherapy appears to be a beneficial therapeutic modality for improving cortical excitability and some clinical outcomes in patients with stroke.     

To act or not to act. Neural correlates of executive control of learned motor behavior

Successful behavior requires contextual modulation of learned "programs", that is, the retrieval or nonretrieval (inhibition) of behavioral elements depending on situative context. Here we report neural correlates of these elementary aspects of behavior as identified with functional magnetic resonance imaging (fMRI). Inhibition of a "ready-to-go" behavioral program was represented in the brain by reduction of net synaptic activity in the cerebro-cerebellar pathway. The metabolic correlate of inhibition was a multifocal (premotor, primary sensorimotor, superior parietal, cingulate cortex, and cerebellum) decrease of the blood oxygenation level-dependent (BOLD) signal to below the resting state (negative BOLD) with a concomitant decrease of motor cortical excitability. The reverse was true for retrieval. We propose that contextual modulation of learned behavioral programs depends on an interplay of focal increases and decreases of neural activity and that the inhibitory changes are reflected by negative BOLD responses in an extended cerebro-cerebellar network of sensorimotor structures.