Contralateral Motor Cortex Research Articles

Modulation of quadriceps corticospinal excitability by femoral nerve stimulation

IntroductionWe explored the conditioning effect of a percutaneous electrical pulse of the femoral nerve on cortical motor evoked responses in the rectus femoris muscle. MethodsCorticospinal excitability of rectus femoris muscle was measured in sixteen healthy subjects, when a single transcranial magnetic pulse was preceded by an electrical femoral nerve stimulus, using twelve inter-stimulus intervals (from 10 to 275ms). We also evaluated the effects of the intensities of the transcranial magnetic and of the electrical pulses. ResultsQuadriceps motor evoked potentials were inhibited and facilitated when a single femoral nerve electrical stimulus was delivered at inter-stimulus intervals of 25ms and 150ms, respectively. The facilitation was reduced when low electrical intensity was used, while the inhibition decreased with high intensity transcranial magnetic pulse. ConclusionAfferent inputs of a femoral stimulation modulate the responses elicited by transcranial magnetic pulses of the contralateral quadriceps motor cortex. This modulation indicates a sensorimotor integration of proximal lower limb muscles that may be mediated via different types of afferents. This could be of relevance for studies that explore the role of lower limb muscles in postural control and balance.

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug’s side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

Neuroplasticity Associated With Anterior Cruciate Ligament Reconstruction.

Study Design Controlled laboratory study. Background Anterior cruciate ligament (ACL) injury may result in neuroplastic changes due to lost mechanoreceptors of the ACL and compensations in neuromuscular control. These alterations are not completely understood. Assessing brain function after ACL injury and anterior cruciate ligament reconstruction (ACLR) with functional magnetic resonance imaging provides a means to address this gap in knowledge. Objective To compare differences in brain activation during knee flexion/extension in persons who have undergone ACLR and in matched controls. Methods Fifteen participants who had undergone left ACLR (38.13 ± 27.16 months postsurgery) and 15 healthy controls matched on age, sex, height, mass, extremity dominance, education level, sport participation, and physical activity level participated. Functional magnetic resonance imaging data were obtained during a unilateral knee motor task consisting of repeated cycles of knee flexion and extension. Results Participants who had undergone ACLR had increased activation in the contralateral motor cortex, lingual gyrus, and ipsilateral secondary somatosensory area and diminished activation in the ipsilateral motor cortex and cerebellum when compared to healthy matched controls. Conclusion Brain activation for knee flexion/extension motion may be altered following ACLR. The ACLR brain activation profile may indicate a shift toward a visual-motor strategy as opposed to a sensory-motor strategy to engage in knee movement. Level of Evidence Cohort, level 3. J Orthop Sports Phys Ther 2017;47(3):180-189. Epub 5 Nov 2016. doi:10.2519/jospt.2017.7003.

Beta-band activity and connectivity in sensorimotor and parietal cortex are important for accurate motor performance

Accurate motor performance may depend on the scaling of distinct oscillatory activity within the motor cortex and effective neural communication between the motor cortex and other brain areas. Oscillatory activity within the beta-band (13–30Hz) has been suggested to provide distinct functional roles for attention and sensorimotor control, yet it remains unclear how beta-band and other oscillatory activity within and between cortical regions is coordinated to enhance motor performance. We explore this open issue by simultaneously measuring high-density cortical activity and elbow flexor and extensor neuromuscular activity during ballistic movements, and manipulating error using high and low visual gain across three target distances. Compared with low visual gain, high visual gain decreased movement errors at each distance. Group analyses in 3D source-space revealed increased theta-, alpha-, and beta-band desynchronization of the contralateral motor cortex and medial parietal cortex in high visual gain conditions and this corresponded to reduced movement error. Dynamic causal modeling was used to compute connectivity between motor cortex and parietal cortex. Analyses revealed that gain affected the directionally-specific connectivity across broadband frequencies from parietal to sensorimotor cortex but not from sensorimotor cortex to parietal cortex. These new findings provide support for the interpretation that broad-band oscillations in theta, alpha, and beta frequency bands within sensorimotor and parietal cortex coordinate to facilitate accurate upper limb movement. Summary statementOur findings establish a link between sensorimotor oscillations in the context of online motor performance in common source space across subjects. Specifically, the extent and distinct role of medial parietal cortex to sensorimotor beta connectivity and local domain broadband activity combine in a time and frequency manner to assist ballistic movements. These findings can serve as a model to examine whether similar source space EEG dynamics exhibit different time-frequency changes in individuals with neurological disorders that cause movement errors.

Viewpoint: New Thoughts on Facilitation of Muscle Strengthening

Increase in efficacy of muscle strengthening is an important issue in the field of sport science. Musclestrengthening is credited with potentiation of muscle strength and muscle endurance, adding to motorperformance, fatigue resistance, as well as reduction in sport injuries. Muscle strength increases after trainingresult from structural changes in muscle fibers and adaptation of neural system. Traditional muscle strengtheningguided by the principles of specificity, overload, and arrangement often highlight structural changes in musclefibers and function benefits associated with training. However, little is concerned how to level up muscularcapacity through facilitation of neuronal excitability, such as alteration in efficacy of muscle strengthening withcentral modulation of cortical neuron. Research of direct control over cortical excitability are reminiscent ofanimal studies in the laboratory using the rodents and primates. It seems not easy to tune cortical excitability ofthe human, on account of ethical issues and technique barriers in the laboratory. For advancements of transcranialmagnetic stimulation and transcranial direct current stimulation (tDCS) in the recent years, changes in corticalexcitability of human in a non-harmful and painless manner become feasible. In particular, tDCS is spotlightedfor convenient application and lower price. tDCS drives low-intensity current (< 2 mA) to the cortex throughthe skull, producing acute effect and after effect on the cortex respectively (Lang et al., 2005; Nitsche et al.,2005). Acute effect is an immediate electrophysiological response of the cortical neurons. The anodal stimulationincreases the neuronal excitability of the area being stimulated, as the positive current causes a depolarization ofthe resting membrane potential of cortical neurons. On the contrary, cathodal stimulation decreases the neuronalexcitability of the area being stimulated. Interestingly, excitation of inhibition of cortical excitability withtDCS persists for an hour once the stimulation has ended. The phenomenon is called after effect, in relation toconcentration changes in neurotransmitters of the brain that effect on the NMDA and GABA receptors. Scholarsin different fields start to use the non-invasive brain stimulation techniques in many fields with several worthnotingimplications, including depression prevention (Brunoni et al., 2016; Nitsche, Boggio, Fregni, & PascualLeone,2009), pain relief (Brasil-Neto, 2016; O’Connell, Wand, Marston, Spencer, & Desouza, 2011), and motorrestoration of neurological victims (D’Agata et al., 2016; Stagg et al., 2012). Of particular note is the use of tDCSfor improving efficacy of muscle strengthening (Hendy, Teo, & Kidgell, 2015; Washabaugh, Santos, Claflin, &Krishnan, 2016). Despite some inconsistencies in parametric setting of the electrical stimulation, positive currentis always applied over the contralateral motor cortex in the training session (Langhorne, Bernhardt, & Kwakkel,2011). The increase in cortical excitability with the positive current is thought to associate with a superiorefficacy of muscle strengthening. Aforementioned evidence collectively gives us some inputs for future study,such as how to optimize efficacy of muscle strengthening of different training modes with tDCS? How to resistSports ＆ Exercise ResearchVol. 18, No. 3, i-v (September, 2016)DOI:10.5297/ser.1803.editorialivIng-Shiou Hwang vexercise-induced fatigue with tDCS? How to train the muscles that are difficult to be exercised with traditionalapproaches? Can tDCS help with skill advancement and injury prevention of the athletes? The message ofthe work is hereby to provide potential readers of the Journal a preliminary thought to promote athletes’competitiveness with practical values.

Motor Experience Reprograms Development of a Genetically-Altered Bilateral Corticospinal Motor Circuit.

Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives. This mouse develops dense ipsilateral CST projections, a bilateral motor cortex motor representation, and bilateral motor phenotypes. Together these phenotypes can be used as readouts of corticospinal system organization and function and the changes brought about by experience. The Emx1-Cre:EphA4tm2Kldr mouse shares features with the common developmental disorder cerebral palsy: bilateral voluntary motor impairments and bilateral CST miswiring. Emx1-Cre:EphA4tm2Kldr mice with typical motor experiences during development display the bilateral phenotype of “mirror” reaching, because of a strongly bilateral motor cortex motor representation and a bilateral CST. By contrast, Emx1-Cre:EphA4tm2Kldr mice that experienced unilateral forelimb constraint from P1 to P30 and tested at maturity had a more contralateral motor cortex motor representation in each hemisphere; more lateralized CST projections; and substantially more lateralized/independent reaching movements. Changes in CST organization and function in this model can be explained by reduced synaptic competition of the CST from the side without developmental forelimb motor experiences. Using this model we show that unilateral constraint largely abrogated the effects of the genetic mutation on CST projections and thus demonstrates how robust and persistent experience-dependent development can be for the establishment of corticospinal system connections and voluntary control. Further, our findings inform the mechanisms of and strategies for developing behavioral therapies to treat bilateral movement impairments and CST miswiring in cerebral palsy.

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia.

To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities. Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients. Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients. The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality. The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias.

Activity in primary motor cortex during action observation covaries with subsequent behavioral changes in execution.

IntroductionObserving someone else perform a movement facilitates motor planning, execution, and motor memory formation. Rate, an important feature in the execution of repeated movements, has been shown to vary following movement observation although the underlying neural mechanisms are unclear. In the current study, we examined how the rate of self‐paced index finger pressing is implicitly modified following passive observation of a similar action performed at a different rate.MethodsFifty subjects performed a finger pressing sequence with their right hand at their own pace before and after passive observation of either a 1‐min video depicting the task performed at 3 Hz by someone else or a black screen. An additional set of 15 subjects performed the task in an MRI scanner.ResultsAcross all 50 subjects, the spontaneous execution rate prior to video observation had a bimodal distribution with modes around 2 and 4 Hz. Following video observation, the slower subjects performed the task at an increased rate. In the 15 subjects who performed the task in the MRI scanner, we found positive correlation between fMRI signal in the left primary motor strip during passive video observation and subsequent behavioral changes in task performance rate.ConclusionWe conclude that observing someone else perform an action at a higher rate implicitly increases the spontaneous rate of execution, and that this implicit induction is mediated by activity in the contralateral primary motor cortex.

Functional connectivity in the neuromuscular system underlying bimanual coordination

Neural synchrony has been suggested as a mechanism for integrating distributed sensorimotor systems involved in coordinated movement. To test the role of corticomuscular and intermuscular coherence in bimanual coordination, we experimentally manipulated the degree of coordination between hand muscles by varying the sensitivity of the visual feedback to differences in bilateral force. In 16 healthy participants, cortical activity was measured using EEG and muscle activity of the flexor pollicis brevis of both hands using high-density electromyography (HDsEMG). Using the uncontrolled manifold framework, coordination between bilateral forces was quantified by the synergy index RV in the time and frequency domain. Functional connectivity was assessed using corticomuscular coherence between muscle activity and cortical source activity and intermuscular coherence between bilateral EMG activity. The synergy index increased in the high coordination condition. RV was higher in the high coordination condition in frequencies between 0 and 0.5 Hz; for the 0.5- to 2-Hz frequency band, this pattern was inverted. Corticomuscular coherence in the beta band (16-30 Hz) was maximal in the contralateral motor cortex and was reduced in the high coordination condition. In contrast, intermuscular coherence was observed at 5-12 Hz and increased with bimanual coordination. Within-subject comparisons revealed a negative correlation between RV and corticomuscular coherence and a positive correlation between RV and intermuscular coherence. Our findings suggest two distinct neural pathways: 1) corticomuscular coherence reflects direct corticospinal projections involved in controlling individual muscles; and 2) intermuscular coherence reflects diverging pathways involved in the coordination of multiple muscles.

Effects of Theta Burst Stimulation on Suprahyoid Motor Cortex Excitability in Healthy Subjects.

Continuous theta burst stimulation (cTBS) and intermittent TBS (iTBS) are powerful patterns of repetitive transcranial magnetic stimulation (rTMS), with substantial potential for motor function rehabilitation post-stroke. However, TBS of suprahyoid motor cortex excitability has not been investigated. This study investigated TBS effects on suprahyoid motor cortex excitability and its potential mechanisms in healthy subjects. Thirty-five healthy subjects (23 females; mean age = 21.66 ± 1.66 years) completed three TBS protocols on separate days, separated by at least one week. A stereotaxic neuronavigation system facilitated accurate TMS positioning. Left and right suprahyoid motor evoked potentials (SMEP) were recorded using single-pulse TMS from the contralateral suprahyoid motor cortex before stimulation (baseline) and 0, 15, and 30 min after stimulation. The SMEP latency and amplitude were analyzed via repeated measures analysis of variance. cTBS suppressed ipsilateral suprahyoid motor cortex excitability and activated the contralateral suprahyoid motor cortex. iTBS facilitated ipsilateral suprahyoid motor cortex excitability; however, it did not affect the contralateral excitability. iTBS eliminated the inhibitory effect caused by cTBS applied to the contralateral suprahyoid motor cortex. TBS had no significant effect on the latencies of bilateral SMEP. TBS effects on suprahyoid motor cortex excitability lasted a minimum of 30 min. TBS effectively regulates suprahyoid motor cortex excitability. Suppression of excitability in one hemisphere leads to further activation of the corresponding contralateral motor cortex. iTBS reverses the inhibitory effect induced by cTBS of the contralateral suprahyoid motor cortex.

Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity.

Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level.

EP 78. Probabilistic imaging of motor projections of dentate nucleus as target structure for deep brain stimulation in tremor

Objective As previously described ( [Coenen et al., 2014] , [Coenen et al., 2011] ), deep brain stimulation of dentate-rubro-thalamo-(cortical) (DRT(C)) pathway, efferent motor projection of dentate nucleus, leads to improvement of tremor symptoms. Visualization of DRT (C), as proposed by several authors ( [Coenen et al., 2011] , [Keser et al., 2015] ), reconstructs connections between dentate nucleus (DN) and ruber nucleus (RN) using deterministic diffusion tensor tractography. However tracer primate studies show that motor projections read spread more than classically described pathway in ruber nucleus ( Dum and Strick, 2003 ). Well known is also that tremor suppressing effects are seen after deep brain stimulation of caudal zona incerta ( Fytagoridis et al., 2012 ) (cZI), which is dorsolateral to RN. We propose alternative way of DRT visualization with probabilistic connectivity evaluation between DN and anatomically defined ROI of hand and leg projection of primary motor cortex (PMC) on the ipsilateral side. Materials and methods We included MRI data of 16 Patients with essential tremor. DTI Imaging with 30 directions as well as 3D turbo spin echo and 3D mprage sequences produced on 1,5T Siemens Avanto scanner. Manual segmentation of seed regions of interest (ROI) in DN and in PMC was done as start–end landmarks of DRT (C). Reconstruction of pyramidal tract is done using PMC-ROI and medulla oblongata ROI. Reconstruction of probabilistic tractography maps was done in FSL Software (FMRIB, Oxford, UK). Tractography results transferred to standard MNI152 space, and mean images calculated (NPM, Mricron Software). Tractography result was analyzed using MNI152 based atlas tools. Results Connectivity maps showed high connectivity values inside of DRT (C), demonstrating similar path distribution and course in brainstem and thalamus. Tractography was able to visualize little connectivity to the contralateral motor cortex because of low resolution to depict fibers in decussation of upper cerebellar peduncle, as already reported from other authors ( Jbabdi et al., 2015 ). Crossed fibers located anterolatheral of those, which not cross. Fiber course differed from other tractography results in additional fibers going laterally from rubber nucleus. Conclusions Probabalistic tractography can reconstruct motor projections of DN. Even if more sophisticated to produce, probabilistic connectivity maps provide quantitative connection probability, hotspot of which can be used for stereotactic target planning. Further studies to compare deterministic and probabilistic approach to map DRT(C) are needed.

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients’ characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies.

Forelimb training drives transient map reorganization in ipsilateral motor cortex

Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury.

Variation in left posterior parietal-motor cortex interhemispheric facilitation following right parietal continuous theta-burst stimulation in healthy adults

Spatial neglect is modeled on an imbalance of interhemispheric inhibition (IHI); however evidence is emerging that it may not explain neglect in all cases. The aim of this study was to investigate the IHI imbalance model of visual neglect in healthy adults, using paired pulse transcranial magnetic stimulation to probe excitability of projections from posterior parietal cortex (PPC) to contralateral primary motor cortex (M1) bilaterally. Motor-evoked potentials (MEPs) were recorded from the first dorsal interossei and facilitation was determined as ratio of conditioned to non-conditioned MEP amplitude. A laterality index reflecting the balance of excitability between the two hemispheres was calculated. A temporal order judgment task (TOJ) assessed visual attention. Continuous theta-burst stimulation was used to transiently suppress right parietal cortex activity and the effect on laterality and judgment task measured, along with associations between baseline and post stimulation measures. Stimulation had conflicting results on laterality, with most participants demonstrating an effect in the negative direction with no decrement in the TOJ task. Correlation analysis suggests a strong association between laterality direction and degree of facilitation of left PPC-to right M1 following stimulation (r=.902), with larger MEP facilitation at baseline demonstrating greater reduction (r=−.908). Findings indicate there was relative balance between the cortices at baseline but right PPC suppression did not evoke left PPC facilitation in most participants, contrary to the IHI imbalance model. Left M1 facilitation prior to stimulation may predict an individual’s response to continuous theta-burst stimulation of right PPC.

MB-96IMPAIRED NEURAL FUNCTION DURING VISUAL-MOTOR PERFORMANCE IN CHILDREN TREATED FOR BRAIN TUMOURS

MB-96. IMPAIRED NEURAL FUNCTION DURING VISUAL-MOTOR PERFORMANCE IN CHILDREN TREATED FOR BRAIN TUMOURS Sonya Bells1, Colleen Dockstader1, Suzanne Laughlin3, Eric Bouffet2, Jovanka Skocic1, and Donald Mabbott1; The Hospital for Sick Children, Department of Psychology, Toronto, ON, Canada; The Hospital for Sick Children, Department of Haematology/Oncology, Toronto, ON, Canada; The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON, Canada Children treated with cranial radiation therapy for brain tumours exhibit substantial cognitive deficits that may be mediated by impaired neural functioning. We used magnetoencephalography to investigate whether aberrant neural oscillations are present in pediatric brain tumour survivors compared to healthy children during a visual-motor reaction time task. MEG recording (151 channels, VSM MedTech) was acquired for 9 previously irradiated patients and age-matched controls during the visual-motor reaction time task (100 trials in total). Reaction time (RT) was measured along with localized power changes within the visual and motor cortex using beamformer analysis. Patients showed a significantly delayed RT compared to controls (t(2,9) 1⁄4 2.68, p , 0.05). Beamformer analysis revealed that relative to controls, patients had muted event-related desynchrony and synchrony in the beta (13-29 Hz) and alpha (8-12 Hz) bandwidths in motor and visual cortex and potentiated high gamma activity (50-100 Hz) in the contralateral motor cortex. Furthermore, we found differences in peak gamma frequency of the visually-induced oscillations. Peak frequency was measured in the low gamma range (30-50 Hz) in patients and in the high gamma range (50-100 Hz) in controls. Our findings indicate that aberrant neural responses, characterized by reduced alpha and beta power and increased gamma power within the contralateral motor area, and reduced peak gamma in visual areas, underlie impaired visual-motor reaction time in patients. Gamma-band oscillations play an important role in visual processing and are associated with measures of cortical thickness. These oscillatory results may reflect structural differences between these two populations. Neuro-Oncology 18:iii97–iii122, 2016. doi:10.1093/neuonc/now076.92 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modulation of Functional Connectivity and Activation during Preparation for Hand Movement

OCCUPATIONAL APPLICATIONS Our results illustrate the enhanced functional connectivity between motor-related brain regions and high-level cognitive brain regions during the transition period between rest and hand movements. These results suggest that the sensorimotor network is interacting with prefrontal areas during the transition period to maintain the preparation state. Both actual movement and the transition period without actual movement modulate brain activities. Capturing the detailed relationship of movement intention could be utilized to improve precision and latency of anticipation-based brain–computer interfaces. Furthermore, consistent with the neuroergonomic approach, this study demonstrates that functional near-infrared spectroscopy is a suitable tool for region-specific, task-related, and resting-state functional connectivity analysis. Our findings could enhance the development of more intuitive and natural interfaces between human and machine systems in diverse areas. The approach presented here could help create assistive devices that perceive and predict operators' intention of movements.TECHNICAL ABSTRACT Introduction: Traditional and new generations of neuroimaging techniques allow observing the modulation of brain activities during transition periods between rest and physical movement execution. A thorough understanding of the brain activity and functional connectivity changes during these transitions could contribute to increasing the precision and decreasing the latency of anticipation-based brain–computer interfaces, and improving human-system integration in general. Consistent with the neuroergonomic approach, functional near-infrared spectroscopy can monitor the outer cortex during extensive physical movement and in realistic settings using wearable and portable sensors. Methods: In this study, 19 healthy subjects were monitored with functional near-infrared spectroscopy during rest, a fist opening and closing task, and the transition period preceding the task. Functional connectivity analysis was used to evaluate how the transition period preceding the task modulated the brain activities. Results: There were several increases in functional connectivity during the transition period, especially between the right dorsolateral prefrontal cortex and the contralateral primary somatosensory and primary motor cortices, as well as the functional connectivity connecting the contralateral primary somatosensory cortex with the ipsilateral primary somatosensory cortex and the primary motor cortex. Regions located in the sensorimotor networks and right dorsolateral prefrontal cortex were also found to be activated during the transition period. Conclusions: These results demonstrate that the sensorimotor network is interacting with the high-level cognitive brain network during the transition period to maintain the preparation state. Furthermore, functional near-infrared spectroscopy is an emerging tool well-suited for region specific task-related and resting-state functional connectivity analysis. The results and the approach presented here suggest that operators' intention to move can be detected before the actual movement, and that could be employed for development of more intuitive and natural interfaces between human and machine systems.

Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial.

We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10Hz (1,200 pulses), 20minutes per day, during 10days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15days after treatment compared with sham stimulation (-53.38 ±53.12% vs -22.93 ±57.16%; mean between-group difference=30.44%, 95% confidence interval, .30-60.58; P=.03). This effect was not significant 30days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15days after treatment (P=.03). The administration of 10Hz rTMS on the contralateral primary motor cortex for 2weeks in traumatic amputees with PLP induced significant clinical improvement in pain. High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.

Brain State-Dependent Closed-Loop Modulation of Paired Associative Stimulation Controlled by Sensorimotor Desynchronization

Background: Pairing peripheral electrical stimulation (ES) and transcranial magnetic stimulation (TMS) increases corticospinal excitability when applied with a specific temporal pattern. When the two stimulation techniques are applied separately, motor imagery (MI)-related oscillatory modulation amplifies both ES-related cortical effects—sensorimotor event-related desynchronization (ERD), and TMS-induced peripheral responses—motor-evoked potentials (MEP). However, the influence of brain self-regulation on the associative pairing of these stimulation techniques is still unclear.Objective: The aim of this pilot study was to investigate the effects of MI-related ERD during associative ES and TMS on subsequent corticospinal excitability.Method: The paired application of functional electrical stimulation (FES) of the extensor digitorum communis (EDC) muscle and subsequent single-pulse TMS (110% resting motor threshold (RMT)) of the contralateral primary motor cortex (M1) was controlled by beta-band (16–22 Hz) ERD during MI of finger extension and applied within a brain-machine interface environment in six healthy subjects. Neural correlates were probed by acquiring the stimulus-response curve (SRC) of both MEP peak-to-peak amplitude and area under the curve (AUC) before and after the intervention.Result: The application of approximately 150 pairs of associative FES and TMS resulted in a significant increase of MEP amplitudes and AUC, indicating that the induced increase of corticospinal excitability was mediated by the recruitment of additional neuronal pools. MEP increases were brain state-dependent and correlated with beta-band ERD, but not with the background EDC muscle activity; this finding was independent of the FES intensity applied.Conclusion: These results could be relevant for developing closed-loop therapeutic approaches such as the application of brain state-dependent, paired associative stimulation (PAS) in the context of neurorehabilitation.

Reliability of Transcranial Magnetic Stimulation Measures

Measurements of motor cortex inhibition and excitability can provide useful insights when assessing pathological damage as well as neuronal recovery from injuries. PURPOSE: The aim of this study was to determine the reliability of single pulse transcranial magnetic stimulation (TMS) measures in men and women. METHODS: Nine (5 female) healthy college age participants were tested at three time points, each separated by one week. Single pulse TMS was delivered to the contralateral motor cortex of the dominant first dorsal interosseous. Resting motor threshold (RMT) and the peak-to-peak amplitude of motor evoked potentials (MEP) at 120% RMT were used to quantify motor cortex excitability. The duration of the cortical silent period (CSP), evoked at 120% RMT while participants maintained a contraction at 50% of maximum force, was used to quantify motor cortex inhibition. Reliability was assessed with the intraclass correlation coefficient (ICC 2,1). RESULTS: There was no significant difference across time (p=0.82; p=0.83; p=0.70) or between sexes (p=0.83; p=0.68; p=0.36) for RMT, MEP, or CSP, respectively. Also, there was no significant sex by time interaction (p≥0.34) for any of the measures. Reliability across days was strong for RMT (R=0.69), and very strong for MEP (R=0.87) and CSP (R=0.95). CONCLUSIONS: These results support the use of single pulse TMS measurements to reliably assess and track motor cortex physiological function in men and women.