Artifact correction and source analysis of early electroencephalographic responses evoked by transcranial magnetic stimulation over primary motor cortex

Analyzing the brain responses to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) is a promising method for the assessment of functional cortical connectivity and excitability of areas accessible to this stimulation. However, until now it has been difficult to analyze the EEG responses during the several tens of milliseconds immediately following the stimulus due to TMS-induced artifacts. In the present study we show that by combining a specially adapted recording system with software artifact correction it is possible to remove a major part of the artifact and analyze the cortical responses as early as 10 ms after TMS. We used this methodology to examine responses of left and right primary motor cortex (M1) to TMS at different intensities. Based on the artifact-corrected data we propose a model for the cortical activation following M1 stimulation. The model revealed the same basic response sequence for both hemispheres. A large part of the response could be accounted for by two sources: a source close to the stimulation site (peaking approximately 15 ms after the stimulus) and a midline frontal source ipsilateral to the stimulus (peaking approximately 25 ms). In addition the model suggests responses in ipsilateral temporo-parietal junction areas (approximately 35 ms) and ipsilateral (approximately 30 ms) and middle (approximately 50 ms) cerebellum. Statistical analysis revealed significant dependence on stimulation intensity for the ipsilateral midline frontal source. The methodology developed in the present study paves the way for the detailed study of early responses to TMS in a wide variety of brain areas.     

Theta-burst stimulation: remote physiological and local behavioral after-effects

Theta-burst stimulation (TBS), a novel repetitive transcranial magnetic stimulation (TMS) protocol, is capable of suppressing the amplitude of contralateral motor-evoked potentials (MEP) for several minutes after the end of a conditioning train over the motor cortex. It remains unknown whether TBS leads to effects on motor cortical excitability when applied to contralateral brain sites distant but connected to motor cortex and whether TBS triggers measurable changes in force control. Subjects received bursts (50 Hz) of three subthreshold magnetic stimuli repeated at 5 Hz for 20 s (TBS-300) or 40 s (TBS-600) over the hand area of the left motor cortex (M1(LEFT)). With TBS-300, conditioning of right motor cortex (M1(RIGHT)), right dorsal premotor cortex (PMd(RIGHT)), and a mid-occipital (MO) region also were tested. Corticospinal excitability was probed by evoking MEPs in abductor pollicis brevis (APB) muscle by single suprathreshold stimuli over M1(LEFT) or M1(RIGHT) before and after TBS. Force level control was assessed in an isometric right thumb abduction task. With TBS-600, the time course of physiological and behavioral changes was monitored. TBS over either of the motor cortices reduced the amplitude of MEP in the contralateral APB and increased it in the ipsilateral APB. In contrast, conditioning TBS over PMd(RIGHT) or MO did not modify MEP size. Post-TBS right thumb force level control was impaired, with contralateral M1(LEFT) stimulation only, for a duration of at least 5 min. TBS may induce remote physiological effects and reveals local functional properties of the underlying brain region.     

Examining cortical dynamics and connectivity with simultaneous single-pulse transcranial magnetic stimulation and fast optical imaging

Transcranial magnetic stimulation (TMS) is a widely used experimental and clinical technique that directly induces activity in human cortex using magnetic fields. However, the neural mechanisms of TMS-induced activity are not well understood. Here, we introduce a novel method of imaging TMS-evoked activity using a non-invasive fast optical imaging tool, the event-related optical signal (EROS). EROS measures changes in the scattering of near-infrared light that occur synchronously with electrical activity in cortical tissue. EROS has good temporal and spatial resolution, allowing the dynamics and spatial spread of a TMS pulse to be measured. We used EROS to monitor activity induced in primary motor cortex (M1) by a TMS pulse. Left- and right-hand representations were mapped using standard TMS procedures. Optical sources and detectors mounted on thin rubber patches were then centered on M1 hand representations. EROS was recorded bilaterally from motor cortex while unilateral TMS was simultaneously delivered. Robust ipsilateral EROS activations were apparent within 16 ms of a pulse for TMS delivered to both left and right hemispheres. Clear motor evoked potentials (MEPs) were also elicited by these TMS pulses. Movement artifacts could be excluded as a source of EROS, as no activation was present on short-distance optical channels. For left hemisphere TMS subsequent (40 ms) contralateral activity was also present, presumably due to trans-synaptic propagation of TMS-evoked activity. Results demonstrate that concurrent TMS/EROS is a viable and potentially powerful method for studying TMS-induced activity in the human brain. With further development, this technique may be applied more broadly in the study of the dynamics of causal cortico-cortical connectivity.     

BOLD MRI responses to repetitive TMS over human dorsal premotor cortex

Functional magnetic resonance imaging (fMRI) studies in humans have hitherto failed to demonstrate activity changes in the direct vicinity of transcranial magnetic stimulation (TMS) that cannot be attributed to re-afferent somatosensory feedback or a spread of excitation. In order to investigate the underlying activity changes at the site of stimulation as well as in remote connected regions, we applied short trains of high-intensity (110% of resting motor threshold) and low-intensity (90% of active motor threshold) repetitive TMS (rTMS; 3 Hz, 10 s duration) over the presumed location of the left dorsal premotor cortex (PMd) during fMRI. Signal increases in the direct vicinity of the stimulated PMd were observed during rTMS at 110% RMT. However, positive BOLD MRI responses were observed with rTMS at both 90% and 110% RMT in connected brain regions such as right PMd, bilateral PMv, supplementary motor area, somatosensory cortex, cingulate motor area, left posterior temporal lobe, cerebellum, and caudate nucleus. Responses were generally smaller during low-intensity rTMS. The results indicate that short trains of TMS can modify local hemodynamics in the absence of overt motor responses. In addition, premotor rTMS cannot only effectively stimulate cortico-cortical but also cortico-subcortical connections even at low stimulation intensities.     

Ipsilateral motor cortex activation on functional magnetic resonance imaging during unilateral hand movements is related to interhemispheric interactions

Distal, unilateral hand movements can be associated with activation of both sensorimotor cortices on functional MRI. The neurophysiological significance of the ipsilateral activation remains unclear. We examined 10 healthy right-handed subjects with and without activation of the ipsilateral sensorimotor area during unilateral index-finger movements, to examine ipsilateral, uncrossed-descending pathways and interhemispheric interaction between bilateral motor areas, using transcranial magnetic stimulation (TMS). No subject showed ipsilateral activation during right hand movement. Five subjects showed ipsilateral sensorimotor cortical activation during left hand movement (IpsiLM1). In these subjects, paired-pulse TMS revealed a significant interhemispheric inhibition of the left motor cortex by the right hemisphere that was not present in the 5 subjects without IpsiLM1. Neither ipsilateral MEPs nor ipsilateral silent periods were evoked by TMS in any subjects. Our observation suggests that IpsiLM1 is not associated with the presence of ipsilateral uncrossed-descending projections. Instead, IpsiLM1 may reveal an enhanced interhemispheric inhibition from the right hemisphere upon the left to suppress superfluous, excessive activation.     

Transcranial Magnetic Stimulation Can Be Used to Test Connections to Primary Motor Areas from Frontal and Medial Cortex in Humans

Surface EMG responses (MEPs) were recorded from the relaxed first dorsal interosseous (FDI) of 16 normal subjects following transcranial magnetic stimulation (TMS) over the hand area of the primary motor cortex. These test responses were conditioned by a subthreshold stimulus applied 2-15 ms beforehand over a range of anterior or medial sites. Stimuli applied 3-5 cm anterior to the hand motor area (site A) or 6 cm anterior to the vertex on the nasion-inion line (site B) inhibited the test responses at short latency. The largest effect was seen when the interstimulus interval was 6 ms and the intensity of the conditioning stimulus was equal to 0.9x active motor threshold (AMT) at the hand area. Increasing the intensity to 1.2x AMT produced facilitation. Suppression of surface EMG responses was mirrored in the behavior of single motor units. Conditioning stimuli had no effect on responses evoked in the active FDI muscle by transcranial electric stimulation of motor cortex nor on forearm flexor H reflexes even though MEPs in the same muscle were suppressed at appropriate interstimulus intervals. We conclude that low-intensity TMS over presumed premotor areas of frontal cortex can engage corticocortical connections to the primary motor hand area.     

Combined functional MRI and tractography to demonstrate the connectivity of the human primary motor cortex in vivo

In this study, we combined advanced MR techniques to explore primary motor cortex (M1) connectivity in the human brain. We matched functional and anatomical information using motor functional MRI (fMRI) and white matter tractography inferred from diffusion tensor imaging (DTI). We performed coregistered DTI and motor task fMRI in 8 right-handed healthy subjects and in 1 right-handed patient presenting with a left precentral tumour. We used the fast-marching tractography (FMT) algorithm to define 3D connectivity maps within the whole brain, from seed points selected in the white matter adjacent to the location of the maximum of fMRI activation. Connectivity maps were then anatomically normalised and analysed using statistical parametric mapping software (SPM99) allowing group comparisons (left versus right hemisphere in control subjects and patient versus control subjects). The results demonstrated, in all control subjects, strong connections from M1 to the pyramidal tracts, premotor areas, parietal cortices, thalamus, and cerebellum. M1 connectivity was asymmetric, being more extensive in the dominant hemisphere. The patient had differences in M1 connectivity from the control group. Thus, fMRI-correlated DTI-FMT is a promising tool to study the structural basis of functional networks in the human brain in vivo.     

Age-related changes in causal interactions between cortical motor regions during hand grip

Brain activity during motor performance becomes more widespread and less lateralized with advancing age in response to ongoing degenerative processes. In this study, we were interested in the mechanism by which this change in the pattern of activity supports motor performance with advancing age. We used both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to assess age related changes in motor system connectivity during isometric hand grip. Paired pulse TMS was used to measure the change in interhemispheric inhibition (IHI) from contralateral M1 (cM1) to ipsilateral M1 (iM1) during right hand grip. Dynamic Causal Modelling (DCM) of fMRI data was used to investigate the effect of age on causal interactions throughout the cortical motor network during right hand grip. Bayesian model selection was used to identify the causal model that best explained the data for all subjects. Firstly, we confirmed that the TMS and DCM measures both demonstrated a less inhibitory/more facilitatory influence of cM1 on iM1 during hand grip with advancing age. These values correlated with one another providing face validity for our DCM measures of connectivity. We found increasing reciprocal facilitatory influences with advancing age (i) between all ipsilateral cortical motor areas and (ii) between cortical motor areas of both hemispheres and iM1. There were no differences in the performance of our task with ageing suggesting that the ipsilateral cortical motor areas, in particular iM1, play a central role in maintaining performance levels with ageing through increasingly facilitatory cortico-cortical influences.     

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura

To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5 Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5 Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5 Hz-rTMS in the three groups tested. The 5 Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5 Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura.     

Cortical activity in multiple motor areas during sequential finger movements: an application of independent component analysis

Multiple cortical regions such as the supplementary motor area (SMA), premotor cortex (PM), and primary motor cortex (M1) are involved in the sequential execution of hand movements, but it is unclear how these areas collaborate in the preparation and execution of ipsilateral and contralateral hand movements. In this study, we used right-handed subjects to examine the spatial distribution and temporal profiles of motor-related activity during visually cued sequential finger movements by applying independent component analysis (ICA) to event-related functional magnetic resonance imaging (fMRI) signals. The particular merit of the ICA method is that it allows brain activity in individual subjects to be elucidated without making a priori assumptions about the anatomical areas that are activated or the temporal profile of activity. By applying ICA, we found that (1) the SMA contributed to both the preparation and execution of movements of the right and left hand; (2) the left M1 and dorsal premotor cortex (PMd) contributed to both the preparation and execution of movements of the right and left hand, whereas the right M1 and PMd contributed mainly to the execution of movements of the left hand; (3) pre-SMA areas were activated in some subjects in concert with the posterior parietal and prefrontal cortex; and (4) fMRI signals over superficial cortical draining veins could be distinguished from cortical activation. We suggest that ICA is useful for categorizing distributed task-related activities in individual subjects into several spatially independent activities that represent functional units in motor control.     

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.     

小脑间歇性θ短阵脉冲刺激对健康人双侧大脑运动皮质兴奋性的调控

目的:研究小脑间歇性θ短阵脉冲刺激(iTBS)对双侧大脑运动皮质M1区兴奋性的影响及持续时间。方法:根据刺激部位的不同,按随机数字表法将纳入的20例青年健康受试者分为左侧小脑iTBS组和右侧小脑iTBS组,每组10例。所有受试者在进行所属组别的刺激模式干预前,先测量双侧大脑M1区静息运动阈值(RMT)及运动诱发电位(M...     

针刺曲池、外关穴调节长时程增强样脑可塑性的研究

目的:观察单侧针刺曲池穴、外关穴的不同针刺状态对健康受试者双侧运动皮层(M1)长时程增强(LTP)样脑可塑性的影响。方法:纳入18名健康受试者,取右侧曲池、外关穴,给予常规普通针刺,进针后行针,得气为度。于针刺前15 min、进针后30 min及拔针后20 min分别使用经颅磁刺激运动诱发电位(TMSMEP)检测皮层兴奋性,观察单侧针刺对成对关联刺激(PAS)诱导LTP脑可塑性的影响。操作方法:①TMSMEP的诱导:进行TMS刺激点定位,找到以最小的刺激强度产生最大MEP波幅的位置,即为FDI皮层运动点;并使用TMS外固定架固定线圈、激光定位仪监测。②检测静息运动诱发电位阈值(rMT):基于FDI对应的皮层运动点,寻找给予10次TMS刺激能够产生至少5个MEP波幅≥50μV的刺激强度,记录为rMT。③短潜伏期尺神经体感诱发电位的测定:刺激电极置于FDI肌腹,阴极在近端,刺激电流5~10 mA,刺激强度为食指轻微抽动为宜。④PAS-LTP脑可塑性的诱导:使用电刺激加磁刺激进行诱导,共200对刺激。每位受试者需进行8次检测,每次约80 min。2次检测需间隔1周,以避免针刺后效应影响试验结果。结果:①与针刺前比较,留针时针刺对侧M1区MEP波幅比降低,针刺同侧M1区MEP波幅比升高;拔针后,针刺双侧M1区MEP波幅比均升高;差异均有统计学意义(P<0.01)。②PAS诱导后,留针时针刺同侧M1区MEP波幅升高;起针后,针刺双侧M1区MEP波幅均升高;差异均有统计学意义(P<0.01)。结论:单侧单次针刺曲池、外关穴不同针刺状态(留针、拔针后)对双侧LTP脑可塑性的影响不同,可以通过调节皮层兴奋性特异性改变双侧皮层的可塑性。     

Relationship between responses to contra- and ipsilateral stimuli in the human second somatosensory cortex SII.

We studied the interaction between responses to contra- and ipsilateral stimuli in the human second somatosensory cortex SII by recording somatosensory evoked magnetic fields (SEFs) from 8 healthy subjects with a 122-channel whole-scalp SQUID magnetometer. Right (R) and left (L) median nerves were electrically stimulated at the wrists at intensities exceeding the motor threshold. In each stimulus sequence, the four equiprobable pairs (L-L, R-R, L-R, R-L) were presented in a random order once every 2 s, with a 300-ms interstimulus interval within the pair. The responses were modelled with a four-dipole model, with current dipoles located in the SI and SII cortices of both hemispheres. The SII responses peaked around 85-120 ms and responses to the 1st (2nd) stimulus on the pair were on average 2 (12) ms earlier and about 3 (2.5) times stronger for contralateral than ipsilateral stimuli. Independently of the condition, the 2nd response always peaked later than the 1st; the mean delay was 16 ms. The responses to the 2nd stimulus depended only slightly on the type of the 1st: the latency increased more and the amplitude decreased less after different than identical 1st stimuli. These results suggest that neuronal activations due to contra- and ipsilateral stimuli overlap strongly in the human SII cortex.     

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.     

Time course and spatial distribution of fMRI signal changes during single-pulse transcranial magnetic stimulation to the primary motor cortex

Simultaneous transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) may advance the understanding of neurophysiological mechanisms of TMS. However, it remains unclear if TMS induces fMRI signal changes consistent with the standard hemodynamic response function (HRF) in both local and remote regions. To address this issue, we delivered single-pulse TMS to the left M1 during simultaneous recoding of electromyography and time-resolved fMRI in 36 healthy participants. First, we examined the time-course of fMRI signals during supra- and subthreshold single-pulse TMS in comparison with those during voluntary right hand movement and electrical stimulation to the right median nerve (MNS). All conditions yielded comparable time-courses of fMRI signals, showing that HRF would generally provide reasonable estimates for TMS-evoked activity in the motor areas. However, a clear undershoot following the signal peak was observed only during subthreshold TMS in the left M1, suggesting a small but meaningful difference between the locally and remotely TMS-evoked activities. Second, we compared the spatial distribution of activity across the conditions. Suprathreshold TMS-evoked activity overlapped not only with voluntary movement-related activity but also partially with MNS-induced activity, yielding overlapped areas of activity around the stimulated M1. The present study has provided the first experimental evidence that motor area activity during suprathreshold TMS likely includes activity for processing of muscle afferents. A method should be developed to control the effects of muscle afferents for fair interpretation of TMS-induced motor area activity during suprathreshold TMS to M1.     

Two different reorganization patterns after rehabilitative therapy: an exploratory study with fMRI and TMS

We used two complementary methods to investigate cortical reorganization in chronic stroke patients during treatment with a defined motor rehabilitation program. BOLD ("blood oxygenation level dependent") sensitive functional magnetic resonance imaging (fMRI) and intracortical inhibition (ICI) and facilitation (ICF) measured with transcranial magnetic stimulation (TMS) via paired pulse stimulation were used to investigate cortical reorganization before and after "constraint-induced movement therapy" (CI). The motor hand function improved in all subjects after CI. BOLD signal intensity changes within affected primary sensorimotor cortex (SMC) before and after CI showed a close correlation with ICI (r = 0.93) and ICF (r = 0.76) difference before and after therapy. Difference in number of voxels and ICI difference before and after CI also showed a close correlation (r = 0.92) in the affected SMC over the time period of training. A single subject analysis revealed that patients with intact hand area of M1 ("the hand knob") and its descending motor fibers (these patients revealed normal motor evoked potentials [MEP] from the affected hand) showed decreasing ipsilesional SMC activation which was paralleled by an increase in intracortical excitability. This pattern putatively reflects increasing synaptic efficiency. When M1 or its descending pyramidal tract was lesioned (MEP from the affected hand was pathologic) ipsilesional SMC activation increased, accompanied by decreased intracortical excitability. We suggest that an increase in synaptic efficiency is not possible here, which leads to reorganization with extension, shift and recruitment of additional cortical areas of the sensorimotor network. The inverse dynamic process between both complementary methods (activation in fMRI and intracortical excitability determined by TMS) over the time period of CI illustrates the value of combining methods for understanding brain reorganization.     

General indices to characterize the electrical response of the cerebral cortex to TMS

Transcranial magnetic stimulation (TMS) combined with simultaneous high-density electroencephalography (hd-EEG) represents a straightforward way to gauge cortical excitability and connectivity in humans. However, the analysis, classification and interpretation of TMS-evoked potentials are hampered by scarce a priori knowledge about the physiological effect of TMS and by lack of an established data analysis framework. Here, we implemented a standardized, data-driven procedure to characterize the electrical response of the cerebral cortex to TMS by means of three synthetic indices: significant current density (SCD), phase-locking (PL) and significant current scattering (SCS). SCD sums up the amplitude of all significant currents induced by TMS, PL reflects the ability of TMS to reset the phase of ongoing cortical oscillations, while SCS measures the average distance of significantly activated sources from the site of stimulation. These indices are aimed at capturing different aspects of brain responsiveness, ranging from global cortical excitability towards global cortical connectivity. We analyzed the EEG responses to TMS of Brodmann's area 19 at increasing intensities in five healthy subjects. The spatial distribution and time course of SCD, PL and SCS revealed a reproducible profile of excitability and connectivity, characterized by a local activation threshold around a TMS-induced electric field of 50 V/m and by a selective propagation of TMS-evoked activation from occipital to ipsilateral frontal areas that reached a maximum at 70–100 ms. These general indices may be used to characterize the effects of TMS on any cortical area and to quantitatively evaluate cortical excitability and connectivity in physiological and pathological conditions.     

Investigation of fMRI neurofeedback of differential primary motor cortex activity using kinesthetic motor imagery

Functional MRI neurofeedback (fMRI NF) is an emerging technique that trains subjects to regulate their brain activity while they manipulate sensory stimulus representations of fMRI signals in "real-time". Here we report an fMRI NF study of brain activity associated with kinesthetic motor imagery (kMI), analyzed using partial least squares (PLS), a multivariate analysis technique. Thirteen healthy young adult subjects performed kMI involving each hand separately, with NF training targeting regions of interest (ROIs) in the left and right primary motor cortex (M1). Throughout, subjects attempted to maximize a laterality index (LI) of brain activity-the difference in activity between the contralateral ROI (relative to the hand involved in kMI) and the ipsilateral M1 ROI-while receiving real-time updates on a visual display. Six of 13 subjects were successful in increasing the LI value, whereas the other 7 were not successful and performed similarly to 5 control subjects who received sham NF training. Ability to suppress activity in the ipsilateral M1 ROI was the primary driver of successful NF performance. Multiple PLS analyses depicted activated networks of brain regions involved with imagery, self-awareness, and feedback processing, and additionally showed that activation of the task positive network was correlated with task performance. These results indicate that fMRI NF of kMI is capable of modulating brain activity in primary motor regions in a subset of the population. In the future, such methods may be useful in the development of NF training methods for enhancing motor rehabilitation following stroke.     

fMRI signal decreases in ipsilateral primary motor cortex during unilateral hand movements are related to duration and side of movement

Interactions between the primary motor cortices of each hemisphere during unilateral hand movements appear to be inhibitory, although there is evidence that the strengths of these interactions are asymmetrical. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of motor task duration and hand used on unilateral movement-related BOLD signal increases and decreases in the hand region of primary motor cortex (M1) of each hemisphere in six right-handed volunteers. Significant task-related BOLD signal decreases were observed in ipsilateral M1 during single and brief bursts of unilateral movements for both hands. However, these negative-to-baseline responses were found to intensify with increasing movement duration in parallel with greater task-related increases in contralateral M1. Movement-related BOLD signal decreases in ipsilateral M1 were also stronger for the right, dominant hand than for the left hand in our right-handed subjects. These findings would be consistent with the existence of interhemispheric interactions between M1 of each hemisphere, whereby increased neuronal activation in M1 of one hemisphere induces reduced neuronal activity in M1 of the opposite hemisphere. The observation of a hemispheric asymmetry in inhibition between M1 of each hemisphere agrees well with previous neuroimaging and electrophysiological data. These findings are discussed in the context of current understanding of the physiological origins of negative-to-baseline BOLD responses.