6-Hz primed low-frequency rTMS to contralesional M1 in two cases with middle cerebral artery stroke

This case study contrasted two subjects with stroke who received 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) to the contralesional primary motor area (M1) to disinhibit ipsilesional M1. Functional magnetic resonance imaging (fMRI) showed that the intervention disrupted cortical activation at contralesional M1. Subject 1 showed decreased intracortical inhibition and increased intracortical facilitation following intervention during paired-pulse TMS testing of ipsilesional M1. Subject 2, whose precentral knob was totally obliterated and who did not show an ipsilesional motor evoked potential at pretest, still did not show any at posttest; however, her fMRI did show a large increase in peri-infarct zone cortical activation. Behavioral results were mixed, indicating the need for accompanying behavioral training to capitalize on the brain organization changes induced with rTMS.     

Effective Connectivity of Cortical Sensorimotor Networks During Finger Movement Tasks: A Simultaneous fNIRS,fMRI, EEG Study

Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography—EEG) and hemodynamic (functional near infrared spectroscopy—fNIRS; and functional magnetic resonance imaging—fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O₂Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O₂Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a significantly greater forward than backward information flow between the ROIs. This simultaneous fMRI, fNIRS and EEG study has shown through independent GC analysis of the respective time series that a bi-directional effective connectivity occurs within a cortico-cortical sensorimotor network (SMC, PMC and DLPFC) during finger movement tasks.     

fMRI analysis of ankle movement tracking training in subject with stroke

This study examined whether ankle-movement tracking training could improve ankle function and brain reorganization, evidenced with functional magnetic resonance imagery (fMRI), in a single subject with stroke. Test measurements included self-ratings of functional activities, 15.24 m (50 feet) walk time, ankle range of motion, ankle tracking accuracy, and peak dorsiflexion movement during dorsiflexion phases of tracking. Cortical activation in the frontal and parietal lobes was measured during fMRI with an active voxel count. Additionally, a signal intensity index was determined for the gyrus precentralis (GPrC). Training consisted of 16 sessions of tracking waveforms on a computer screen with ankle motion. Four pretest, four posttest and two follow-up measurements occurred. Data were analyzed by visual inspection and by statistical analysis that examined whether posttest measurements exceeded the pretest mean by at least two standard deviations on at least two consecutive posttest measurements. Posttest results showed that the subjects self report of paretic ankle catches (failure of toes to clear floor during swing phase) during gait were eliminated and that peak dorsiflexion movement improved visually but not statistically. Multiple cortical areas showed increased voxel count statistically, as did the intensity index for GPrC. Follow-up results showed that the ankle catches, peak dorsiflexion movement, and the intensity index remained at the same levels as posttest. Voxel counts returned toward pretest values. We concluded that tracking training produced training effects in both ankle function and brain reorganization.This work was completed at the University of Minnesota, Minneapolis, MN 55455     

Chronic stroke recovery after combined BCI training and physiotherapy: A case report

A case of partial recovery after stroke and its associated brain reorganization in a chronic patient after combined brain computer interface (BCI) training and physiotherapy is presented. A multimodal neuroimaging approach based on fMRI and diffusion tensor imaging was used to investigate plasticity of the brain motor system in parallel with longitudinal clinical assessments. A convergent association between functional and structural data in the ipsilesional premotor areas was observed. As a proof of concept investigation, these results encourage further research on a specific role of BCI on brain plasticity and recovery after stroke.     

fMRI reliability in subjects with stroke

Functional MRI (fMRI) has become one of the most commonly used neuroimaging tools to assess the cortical effects associated with rehabilitation, learning, or disease recovery in subjects with stroke. Despite this, there has been no systematic study of the reliability of the fMR signal in this population. The purpose of this study was to examine the within- and between-session reliability of fMRI in cortical and cerebellar structures in subjects with stroke during a complex, continuous visual motor task performed with the less affected hand. Nine subjects with stroke underwent four testing trials during two sessions separated by three weeks. Subjects performed a drawing task using an MRI compatible joystick while in the MRI. Methods of analysis evaluated included: percent signal intensity change, active voxel count and a voxel by voxel stat value analysis within and between testing sessions. Reliability was determined with Interclass correlation coefficients (ICC) in the following regions of interest: primary motor (M1), primary sensory (S1), premotor cortex (PMC), medial cerebellum (MCB), and lateral cerebellum (LCB). Results indicate that intensity change has superior reliability to the other methods of analysis (Average ICC across brain regions and trials: intensity change: 0.73, voxel count: 0.58, voxel by voxel: 0.67) and that generally with any analysis method, within-session reliability was higher than between-session, as indicated by higher ICC values across brain regions. Overall, when comparing between-session results, moderate to good reliability was obtained with intensity change (ICC: M1: 0.52, S1: 0.80, SMA: 0.78, PMC: 0.94, MCB: 0.86, and LCB: 0.59). These results show good reliability in subjects with stroke when performing a continuous motor task. These findings give confidence for interpreting fMRI test/retest research in subjects with stroke.     

健侧脑感觉运动区在局灶性脑梗死后偏瘫肢体运动功能康复中的作用

目的:探讨局灶性脑梗死后健侧大脑半球感觉运动区在偏瘫上肢运动功能恢复中的作用和意义。方法:前瞻性非随机对照研究。纳入扬州大学附属医院神经内科2015年6月—2017年12月经严格筛选的17例初次发病的纹状体内囊区脑梗死(SCI)伴单侧严重上肢瘫患者作为研究对象(观察组),同时选取15例健康者作为对照组。分别于发病后1周...     

Cortical effect and functional recovery by the electromyography-triggered neuromuscular stimulation in chronic stroke patients

We investigated the effect of electromyography (EMG)-triggered neuromuscular electrical stimulation (NMES; EMG-stim) on functional recovery of the hemiparetic hand and the related cortical activation pattern in chronic stroke patients. We enrolled 14 stroke patients, who were randomly assigned to the EMG-stim (n=7) or the control groups (n=7). The EMG-stim was applied to the wrist extensor of the EMG-stim group for two sessions (30min/session) a day, five times per week for 10 weeks. Four functional tests (box and block, strength, the accuracy index, and the on/offset time of muscle contraction) and functional MRI (fMRI) were performed before and after treatment. fMRI was measured at 1.5T in parallel with timed finger flexion-extension movements at a fixed rate. Following treatment, the EMG-stim group showed a significant improvement in all functional tests. The main cortical activation change with such functional improvement was shifted from the ipsilateral sensorimotor cortex (SMC) to the contralateral SMC. We demonstrated that 10-week EMG-stim can induce functional recovery and change of cortical activation pattern in the hemiparetic hand of chronic stroke patients.     

Functional Magnetic Resonance Imaging of Motor Cortex Activation in Schizophrenia

Previous fMRI studies of sensorimotor activation in schizophrenia have found in some cases hypoactivity, no difference, or hyperactivity when comparing patients with controls; similar disagreement exists in studies of motor laterality. In this multi-site fMRI study of a sensorimotor task in individuals with chronic schizophrenia and matched healthy controls, subjects responded with a right-handed finger press to an irregularly flashing visual checker board. The analysis includes eighty-five subjects with schizophrenia diagnosed according to the DSM-IV criteria and eighty-six healthy volunteer subjects. Voxel-wise statistical parametric maps were generated for each subject and analyzed for group differences; the percent Blood Oxygenation Level Dependent (BOLD) signal changes were also calculated over predefined anatomical regions of the primary sensory, motor, and visual cortex. Both healthy controls and subjects with schizophrenia showed strongly lateralized activation in the precentral gyrus, inferior frontal gyrus, and inferior parietal lobule, and strong activations in the visual cortex. There were no significant differences between subjects with schizophrenia and controls in this multi-site fMRI study. Furthermore, there was no significant difference in laterality found between healthy controls and schizophrenic subjects. This study can serve as a baseline measurement of schizophrenic dysfunction in other cognitive processes.

Graphical Abstract

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Difference of neural connectivity for motor function in chronic hemiparetic stroke patients with intracerebral hemorrhage

Difference of neural connectivity for motor function had been studied by observation of neural activity within gray matter and nucleus using functional neuroimaging techniques. Diffusion tensor imaging (DTI) by a probabilistic tracking is useful for exploration of structural connectivity in the brain. We attempted to investigate difference of neural connectivity for motor function of the affected hand in chronic hemiparetic patients with intracerebral hemorrhage (ICH). Forty-four patients with ICH and 31 normal control subjects were recruited. Diffusion tensor imaging was acquired using a sensitivity-encoding head coil at 1.5 T. Motor function was evaluated using the motricity index (MI) for hand and Modified Brunnstrom Classification (MBC). The presence or absence of a connection was confirmed between the precentral knob of the affected hemisphere and seven areas. Compared with healthy subjects, the patient group showed lower connectivity to the contralesional primary motor cortex, ipsilesional basal ganglia, ipsilesional thalamus, contralesional cerebellum, and ipsilesional medullary pyramid in the affected hemisphere (p < 0.05). Connections to the ipsilesional basal ganglia, ipsilesional thalamus, and ipsilesional medullary pyramid showed positive correlation with MI and MBC (p < 0.05). We found difference of neural connectivity for motor function between chronic hemiparetic patients with ICH and control subjects. Our results suggest that the motor function of the stroke patient is related to neural connectivity between the ipsilesional M1 and the ipsilesional medullary pyramid, ipsilesional basal ganglia, and ipsilesional thalamus.     

Time-resolved fMRI of activation patterns in M1 and SMA during complex voluntary movement

The aim of this study was to use time-resolved functional magnetic resonance imaging (fMRI) to investigate temporal differences in the activation of the supplementary motor area (SMA) and the primary motor cortex (M1). We report data from eight human volunteers who underwent fMRI examinations in a 1.5T Philips Gyroscan ACS-NT MRI scanner. While wearing a contact glove, subjects executed a complex automated sequence of finger movements either spontaneously or in response to external auditory cues. Based on the result of a functional scout scan, a single slice that included the M1 and the SMA was selected for image acquisition (echo planar imaging, repetition time 100 ms, echo time 50 ms, 64 x 64 matrix, 1,000 images). Data were analyzed with a shifting cross-correlation approach using the STIMULATE program and in-house programs written in Interactive Data Language (IDL(TM)). Time-course data were generated for regions of interest in the M1 as well as in the rostral and caudal SMA. Mean time between onset of the finger movement sequence and half-maximum of the signal change in M1 was 3.6 s for the externally cued execution (SD 0.5) and 3.5 s for the spontaneous execution (SD 0.6). Activation in the rostral section of the SMA occurred 0.7 s earlier than it did in the M1 during the externally cued execution and 2.0 s earlier during the spontaneous execution, a difference significant at the P < 0.01 level. Our results indicate that rostral SMA activation precedes M1 activation by varying time intervals in the sub-second range that are determined by the mode of movement initialization. By applying a paradigm that exerts a differential influence on temporal activation, we could ensure that the observed timing differences were not the result of differences in hemodynamic response function.     

Motor learning after stroke: Is skill acquisition a prerequisite for contralesional neuroplastic change?

Limited data directly characterize the dynamic evolution of brain activity associated with motor learning after stroke. The current study considered whether sequence-specific motor skill learning or increasing non-specific use of the hemiparetic upper extremity drive functional reorganization of the contralesional motor cortex after stroke. Eighteen individuals with chronic middle cerebral artery stroke practiced one of two novel motor tasks; a retention test occurred on a separate fifth day. Using the hemiparetic arm, participants performed a serial targeting task during two functional MRI scans (day one and retention). Participants were randomized into either a task-specific group, who completed three additional sessions of serial targeting practice, or a general arm use group, who underwent three training sessions of increased but non-task specific use of the hemiparetic arm. Both groups performed a repeated sequence of responses that may be learned, and random sequences of movement, which cannot be learned. Change in reaction and movement time for the repeated sequence indexed motor learning; shifts in the laterality index (LI) within primary motor cortex (M1) for repeated and random sequences illustrated training effects on brain activity. Task-specific practice of the repeated sequence facilitated motor learning and shifted the LI for M1 as shown by a reduced volume of contralesional cortical activity. Random sequence performance did not stimulate motor learning or alter the LI within the task-specific training group. Further, between-group comparisons showed that increasing general arm use did not induce motor learning or alter brain activity for either random or repeated sequences. Motor skill learning of a repeated sequence altered cortical activation by inducing a more normal, contralateral pattern of brain activation. Our data suggest that task-specific motor learning may be an important stimulant for neuroplastic change and can remediate maladaptive patterns of brain activity after stroke.     

Event-related desynchronization of sensorimotor EEG rhythms in hemiparetic patients with acute stroke

Previous neuroimaging studies based on neurovascular coupling have shown that stroke affects both, strength and spatial extent of brain activation during upper limb movements. Here, we investigated the sub-second amplitude dynamics of a direct neuronal measure, i.e., event-related desynchronization (ERD) of EEG oscillations during finger movements, in patients with acute cortical and subcortical stroke. Acute cortical strokes were found to decrease the ERD of alpha oscillations for the affected pericentral sensorimotor areas compared to a control group. Within the cortical stroke group, the affected hemisphere showed a smaller alpha-ERD compared to the unaffected hemisphere when each was contralateral to the acting hand. Furthermore, when cortical stroke patients moved their paretic hand, the ipsilateral (i.e., contralesional) alpha-ERD was stronger than the contralateral (ipsilesional) ERD. Interestingly, the alpha-ERD amplitude in a hemisphere with a cortical stroke was relatively well preserved for non-paretic hand movements compared to alpha-ERD amplitude for paretic hand movements. This finding provides a new perspective for assessing the rehabilitative potential, which could be utilized through training of the still responsive cortical network, e.g., via enforced use of the paretic hand.     

Coupled bilateral movements and active neuromuscular stimulation: intralimb transfer evidence during bimanual aiming

Motor improvements in chronic stroke recovery accrue from coupled protocols of bilateral movements and active neuromuscular stimulation. This experiment investigated coupled protocols and within-limb transfer between distal and proximal joint combinations. The leading question focused on within-limb transfer of coupled protocols on distal joints to a bimanual aiming task that involved proximal joints. Twenty-six volunteers completed one of three motor recovery protocols according to group assignments: (1) coupled bilateral involved concurrent wrist/finger movements on the unimpaired limb coupled with active stimulation on the impaired limb; (2) unilateral/active stimulation involved neuromuscular electromyogram-triggered stimulation on the impaired wrist/fingers; and (3) no protocol (control group). During the pretest and posttest, subjects performed transverse plane target aiming movements (29 cm) with vision available. The coupled bilateral group showed positive intralimb transfer post-treatment when both arms moved simultaneously. During the posttest, the coupled bilateral group displayed improved movement time, higher peak limb velocity, less variability in peak velocity, and less percentage of total movement time in the deceleration phase than during the pretest. The evidence confirms that within-limb transfer from distal joint training to proximal joint combinations is viable and generalizable in chronic stroke rehabilitation. Moreover, these intralimb transfer findings extend the evidence favoring motor improvements for coupled bilateral protocols during chronic stroke.     

The influence of interval versus continuous exercise on thermoregulation, torso hemodynamics, and finger dexterity in the cold

The purpose of this study was to evaluate how interval (INT) and continuous (CONT) exercise alter body temperatures and manual dexterity in the cold (5°C). Fourteen young men underwent two trials consisting of a 90-min period of acute cold exposure (ACE), 30 min of exercise (INT or CONT), and a 60-min recovery period (REC). Participants donned approximately 1 clo but the hands remained bare for the entire protocol so that a steep decline in dexterity performance occurred prior to the initiation of exercise. INT and CONT were isoenergetic, reflecting 50 ± 1% of each individual’s VO₂ peak. Rectal (Tre) and skin temperatures were monitored continuously and dexterity testing was conducted at ten time points throughout each 3-h trial. In addition, oxygen consumption (VO₂) and torso hemodynamics were assessed via indirect calorimetry and impedance cardiography (ICG), respectively. As expected, finger temperature and dexterity declined during ACE, relative to baseline. Both modes of exercise increased finger temperature and dexterity, relative to ACE. However, CONT was more effective than INT at increasing finger temperature on the dominant hand, which was associated with better dexterity scores during REC. Tre was not different between trials but a significant increase in stroke volume was found following CONT. Perhaps elevated stroke volume during post-exercise REC plays a role in finger rewarming and dexterity performance. Further mechanistic studies are needed to confirm the role of cardiovascular function in the enhancement of manual performance in the cold.     

Reversed lateralization of temporal activation during speech production in thought disordered patients with schizophrenia

BACKGROUND: Formal thought disorder is a core symptom of schizophrenia. It is associated with a reversed lateralization of the superior temporal cortex volume, an area that is implicated in lexical retrieval. We investigated the neural correlates of word retrieval during continuous speech in patients with formal thought disorder using functional magnetic resonance imaging (fMRI). METHODS: Blood oxygenation level dependent (BOLD) contrast was measured with fMRI while six patients with schizophrenia and six healthy control subjects spoke about seven Rorschach inkblots for 3 min each. Subjects produced varying amounts of speech during each run. In a within subject design, the number of words produced was correlated with the BOLD contrast in the two runs in each participant who showed the highest variance of speech output. RESULTS: In control subjects, the amount of speech produced was mainly correlated with activation in the left superior temporal gyrus. In the patient group, the main correlations were in the right superior temporal gyrus. CONCLUSIONS: During the production of continuous speech, patients with formal thought disorder showed a reversed laterality of activation in the superior temporal cortex. This is consistent with findings of perturbed hemispheric interaction in schizophrenia, particularly in patients with formal thought disorder.     

Effects of motor training on the recovery of manual dexterity after primary motor cortex lesion in macaque monkeys

To investigate the effects of postlesion training on motor recovery, we compared the motor recovery of macaque monkeys that had received intensive motor training with those that received no training after a lesion of the primary motor cortex (M1). An ibotenic acid lesion in the M1 digit area resulted in impairment of hand function, with complete loss of digit movement. In the monkeys that had undergone intensive daily training (1 h/day, 5 days/wk) after the lesion, behavioral indexes used to evaluate manual dexterity recovered to the same level as in the prelesion period after 1 or 2 mo of postlesion training period. Relatively independent digit movements, including precision grip (prehension of a small object with finger-to-thumb opposition), were restored in the trained monkeys. Although the behavioral indexes of manual dexterity recovered to some extent in the monkeys without the postlesion training, they remained lower than those in the prelesion period until several months after M1 lesion. The untrained monkeys frequently used alternate grip strategies to grasp a small object with the affected hand, holding food pellets between the tip of the index finger and the dorsum of the thumb. These results suggest that the recovery after M1 lesion includes both use-dependent and use-independent processes and that the recovery of precision grip can be promoted by intensive use of the affected hand in postlesion training.     

Gain control in the response of human visual cortex to plaids

A recent intrinsic signal optical imaging study in tree shrew showed, surprisingly, that the population response of V1 to plaid patterns comprising grating components of equal contrast is predicted by the average of the responses to the individual components (MacEvoy SP, Tucker TR, Fitzpatrick D. Nat Neurosci 12: 637-645, 2009). This prompted us to compare responses to plaids and gratings in human visual cortex as a function of contrast and orientation. We found that the functional MRI (fMRI) blood oxygenation level-dependent (BOLD) responses of areas V1-V3 to a plaid comprising superposed grating components of equal contrast are significantly higher than the responses to a single component. Furthermore, the orientation response profile of a plaid is poorly predicted from a linear combination of the responses to its components. Together, these results indicate that the model of MacEvoy et al. (2009) cannot, without modification, account for the fMRI BOLD response to plaids in human visual cortex.     

Early and late changes in the distal forelimb representation of the supplementary motor area after injury to frontal motor areas in the squirrel monkey

Neuroimaging studies in stroke survivors have suggested that adaptive plasticity occurs following stroke. However, the complex temporal dynamics of neural reorganization after injury make the interpretation of functional imaging studies equivocal. In the present study in adult squirrel monkeys, intracortical microstimulation (ICMS) techniques were used to monitor changes in representational maps of the distal forelimb in the supplementary motor area (SMA) after a unilateral ischemic infarct of primary motor (M1) and premotor distal forelimb representations (DFLs). In each animal, ICMS maps were derived at early (3 wk) and late (13 wk) postinfarct stages. Lesions resulted in severe deficits in motor abilities on a reach and retrieval task. Limited behavioral recovery occurred and plateaued at 3 wk postinfarct. At both early and late postinfarct stages, distal forelimb movements could still be evoked by ICMS in SMA at low current levels. However, the size of the SMA DFL changed after the infarct. In particular, wrist-forearm representations enlarged significantly between early and late stages, attaining a size substantially larger than the preinfarct area. At the late postinfarct stage, the expansion in the SMA DFL area was directly proportional to the absolute size of the lesion. The motor performance scores were positively correlated to the absolute size of the SMA DFL at the late postinfarct stage. Together, these data suggest that, at least in squirrel monkeys, descending output from M1 and dorsal and ventral premotor cortices is not necessary for SMA representations to be maintained and that SMA motor output maps undergo delayed increases in representational area after damage to other motor areas. Finally, the role of SMA in recovery of function after such lesions remains unclear because behavioral recovery appears to precede neurophysiological map changes.     

正常中老年人词语联想任务功能磁共振成像研究

目的 采用功能磁共振成像(fMRI)技术对正常中老年人进行研究,检测与词语联想功能相关脑区的激活特点.方法 采用GE 1.5 T磁共振扫描仪对23例(男12例,女11例)正常中老年人行组块设计的词语联想任务fMRI研究.采用SPM 2软件进行数据处理和统计分析,通过组分析获得平均脑激活图,观察脑激活区的部位和激活强度.结果 12例符合入组条件,激活脑区为运动前区(PMC)、双侧额下回后部(Broca区及Broca镜像区)、双侧辅助运动区(SMA)、左侧顶后皮层、双侧岛叶、双侧扣带回前部、双侧基底节、左侧丘脑以及右侧小脑半球.全脑以左侧PMC激活强度最大.激活强度左侧大于右侧的脑区为额下回后部、背侧PMC及SMA;右侧大于左侧的脑区为腹侧PMC、岛叶、扣带回前部、基底节.结论 中老年人参与运动性语言表达的脑区,由包括Broca区在内的多个脑区组成复杂的神经网络,且相关脑区存在偏侧化现象,以左侧大脑半球和右侧小脑半球激活为主.     

Negative BOLD during tongue movement: A functional magnetic resonance imaging study

The aim of this functional magnetic resonance imaging (fMRI) study was to evaluate negative blood oxygen level-dependent (BOLD) signals during voluntary tongue movement. Deactivated (Negative BOLD) regions included the posterior parietal cortex (PPC), precuneus, and middle temporal gyrus. Activated (Positive BOLD) regions included the primary somatosensory-motor area (SMI), inferior parietal lobule, medial frontal gyrus, superior temporal gyrus, insula, lentiform nucleus, and thalamus. The results were not consistent with previous studies involving unilateral hand and finger movements showing the deactivation of motor-related cortical areas including the ipsilateral MI. The areas of Negative BOLD in the PPC and precuneus might reflect specific neural networks relating to voluntary tongue movement.