Search

Introduction: Functional MRI with spatial resolution in the submillimeter domain enables measurements of activation across cortical layers in humans. This is valuable as different types of cortical computations, e.g., feedforward versus feedback related activity, take place in different cortical layers. Laminar fMRI studies have almost exclusively employed 7T scanners to overcome the reduced signal stability associated with small voxels. However, such systems are relatively rare and only a subset of those are clinically approved. In the present study, we examined if the feasibility of laminar fMRI at 3T could be improved by use of NORDIC denoising and phase regression. Methods: 5 healthy subjects were scanned on a Siemens MAGNETOM Prisma 3T scanner. To assess across-session reliability, each subject was scanned in 3–8 sessions on 3–4 consecutive days. A 3D gradient echo EPI (GE-EPI) sequence was used for BOLD acquisitions (voxel size 0.82 mm isotopic, TR = 2.2 s) using a block design finger tapping paradigm. NORDIC denoising was applied to the magnitude and phase time series to overcome limitations in temporal signal-to-noise ratio (tSNR) and the denoised phase time series were subsequently used to correct for large vein contamination through phase regression. Results and conclusion: NORDIC denoising resulted in tSNR values comparable to or higher than commonly observed at 7T. Layer-dependent activation profiles could thus be extracted robustly, within and across sessions, from regions of interest located in the hand knob of the primary motor cortex (M1). Phase regression led to substantially reduced superficial bias in obtained layer profiles, although residual macrovascular contribution remained. We believe the present results support an improved feasibility of laminar fMRI at 3T.

Background: functional near-infrared spectroscopy (fNIRS) is an increasingly popular tool to study cortical activity during movement and gait that requires further validation. This study aimed to assess (1) whether fNIRS can detect the difficult-to-measure leg area of the primary motor cortex (M1) and distinguish it from the hand area; and (2) whether fNIRS can differentiate between automatic (i.e., not requiring one's attention) and non-automatic movement processes. Special attention was attributed to systemic artifacts (i.e., changes in blood pressure, heart rate, breathing) which were assessed and corrected by short channels, i.e., fNIRS channels which are mainly sensitive to superficial scalp hemodynamics. Methods: Twenty-three seated, healthy participants tapped four fingers on a keyboard or tapped the right foot on four squares on the floor in a specific order given by a 12-digit sequence (e.g., 434141243212). Two different sequences were executed: a beforehand learned (i.e., automatic) version and a newly learned (i.e., non-automatic) version. A 36-channel fNIRS device including 12 short channels covered multiple motor-related cortical areas including M1. The fNIRS data were analyzed with a general linear model (GLM). Correlation between the expected functional hemodynamic responses (i.e. task regressor) and the short channels (i.e. nuisance regressors), necessitated performing a separate short channel regression instead of integrating them in the GLM. Results: Consistent with the M1 somatotopy, we found significant HbO increases of very large effect size in the lateral M1 channels during finger tapping (Cohen's d = 1.35, p

Low-intensity transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique that can modulate the excitability of cortical and deep brain structures with a high degree of focality. Previous human studies showed that TUS decreases motor cortex (M1) excitability measured by transcranial magnetic stimulation (TMS), but whether the effects appear beyond sonication and whether TUS affects the excitability of other interconnected cortical areas is not known. The time course of M1 TUS on ipsilateral and contralateral M1 excitability was investigated in 22 healthy human subjects via TMS-induced motor-evoked potentials. With sonication duration of 500 ms, we found suppression of M1 excitability from 10 ms before to 20 ms after the end of sonication, and the effects were stronger with blocked design compared to interleaved design. There was no significant effect on contralateral M1 excitability. Using ex-vivo measurements, we showed that the ultrasound transducer did not affect the magnitude or time course of the TMS-induced electromagnetic field. We conclude that the online-suppressive effects of TUS on ipsilateral M1 cortical excitability slightly outlast the sonication but did not produce long-lasting effects. The absence of contralateral effects may suggest that there are little tonic interhemispheric interactions in the resting state, or the intensity of TUS was too low to induce transcallosal inhibition.

Haptic object perception begins with continuous exploratory contact, and the human brain needs to accumulate sensory information continuously over time. However, it is still unclear how the primary sensorimotor cortex (PSC) interacts with these higher-level regions during haptic exploration over time. This functional magnetic resonance imaging (fMRI) study investigates time-dependent haptic object processing by examining brain activity during haptic 3D curve and roughness estimations. For this experiment, we designed sixteen haptic stimuli (4 kinds of curves × 4 varieties of roughness) for the haptic curve and roughness estimation tasks. Twenty participants were asked to move their right index and middle fingers along the surface twice and to estimate one of the two features—roughness or curvature—depending on the task instruction. We found that the brain activity in several higher-level regions (e.g., the bilateral posterior parietal cortex) linearly increased as the number of curves increased during the haptic exploration phase. Surprisingly, we found that the contralateral PSC was parametrically modulated by the number of curves only during the late exploration phase but not during the early exploration phase. In contrast, we found no similar parametric modulation activity patterns during the haptic roughness estimation task in either the contralateral PSC or in higher-level regions. Thus, our findings suggest that haptic 3D object perception is processed across the cortical hierarchy, whereas the contralateral PSC interacts with other higher-level regions across time in a manner that is dependent upon the features of the object.

Compatible (positive approaching and negative avoiding) and incompatible (positive avoiding and negative approaching) behavior are of great significance for biological adaptation and survival. Previous research has found that reaction times of compatible behavior are shorter than the incompatible behavior, which is termed the stimulus-response compatibility (SRC) effect. However, the underlying neurophysiological mechanisms of the SRC effect applied to affective stimuli is still unclear. Here, we investigated preparatory activities in both the left and right primary motor cortex (M1) before the execution of an approaching-avoiding behavior using the right index finger in a manikin task based on self-identity. The results showed significantly shorter reaction times for compatible than incompatible behavior. Most importantly, motor-evoked potential (MEP) amplitudes from left M1 stimulation were significantly higher during compatible behavior than incompatible behavior at 150 and 200 ms after stimulus presentation, whereas the reversed was observed for right M1 stimulation with lower MEP amplitude in compatible compared to incompatible behavior at 150 ms. The current findings revealed the compatibility effect at both behavioral and neurophysiological levels, indicating that the affective SRC effect occurs early in the motor cortices during stimulus processing, and MEP modulation at this early processing stage could be a physiological marker of the affective SRC effect.

Electrocorticography (ECoG) based Brain-Computer Interfaces (BCIs) have been proposed as a way to restore and replace motor function or communication in severely paralyzed people. To date, most motor-based BCIs have either focused on the sensorimotor cortex as a whole or on the primary motor cortex (M1) as a source of signals for this purpose. Still, target areas for BCI are not confined to M1, and more brain regions may provide suitable BCI control signals. A logical candidate is the primary somatosensory cortex (S1), which not only shares similar somatotopic organization to M1, but also has been suggested to have a role beyond sensory feedback during movement execution. Here, we investigated whether four complex hand gestures, taken from the American sign language alphabet, can be decoded exclusively from S1 using both spatial and temporal information. For decoding, we used the signal recorded from a small patch of cortex with subdural high-density (HD) grids in five patients with intractable epilepsy. Notably, we introduce a new method of trial alignment based on the increase of the electrophysiological response, which virtually eliminates the confounding effects of systematic and non-systematic temporal differences within and between gestures execution. Results show that S1 classification scores are high (76%), similar to those obtained from M1 (74%) and sensorimotor cortex as a whole (85%), and significantly above chance level (25%). We conclude that S1 offers characteristic spatiotemporal neuronal activation patterns that are discriminative between gestures, and that it is possible to decode gestures with high accuracy from a very small patch of cortex using subdurally implanted HD grids. The feasibility of decoding hand gestures using HD-ECoG grids encourages further investigation of implantable BCI systems for direct interaction between the brain and external devices with multiple degrees of freedom. [ABSTRACT FROM AUTHOR]

• We tested the feasibility of laminar BOLD fMRI at 3T. • NORDIC denoising was used to improve tSNR by a factor of ∼3. • Phase regression reduced macrovascular contamination. • With these tools, layerprofiles could be obtained robustly within and across sessions. • Improved feasibility of 3T laminar fMRI is supported thus increasing its availability. Functional MRI with spatial resolution in the submillimeter domain enables measurements of activation across cortical layers in humans. This is valuable as different types of cortical computations, e.g., feedforward versus feedback related activity, take place in different cortical layers. Laminar fMRI studies have almost exclusively employed 7T scanners to overcome the reduced signal stability associated with small voxels. However, such systems are relatively rare and only a subset of those are clinically approved. In the present study, we examined if the feasibility of laminar fMRI at 3T could be improved by use of NORDIC denoising and phase regression. 5 healthy subjects were scanned on a Siemens MAGNETOM Prisma 3T scanner. To assess across-session reliability, each subject was scanned in 3–8 sessions on 3–4 consecutive days. A 3D gradient echo EPI (GE-EPI) sequence was used for BOLD acquisitions (voxel size 0.82 mm isotopic, TR = 2.2 s) using a block design finger tapping paradigm. NORDIC denoising was applied to the magnitude and phase time series to overcome limitations in temporal signal-to-noise ratio (tSNR) and the denoised phase time series were subsequently used to correct for large vein contamination through phase regression. NORDIC denoising resulted in tSNR values comparable to or higher than commonly observed at 7T. Layer-dependent activation profiles could thus be extracted robustly, within and across sessions, from regions of interest located in the hand knob of the primary motor cortex (M1). Phase regression led to substantially reduced superficial bias in obtained layer profiles, although residual macrovascular contribution remained. We believe the present results support an improved feasibility of laminar fMRI at 3T. [ABSTRACT FROM AUTHOR]

• fNIRS can distinguish between finger and leg movements in the primary motor cortex. • Effect sizes of leg activity are smaller than effect sizes of finger activity. • Leg movements induce systemic fluctuations that should be removed by short channels. • Correlation between tasks and systemic fluctuations results in multicollinearity. • We share a fully-open dataset in BIDS format, including 3D optode positions. functional near-infrared spectroscopy (fNIRS) is an increasingly popular tool to study cortical activity during movement and gait that requires further validation. This study aimed to assess (1) whether fNIRS can detect the difficult-to-measure leg area of the primary motor cortex (M1) and distinguish it from the hand area; and (2) whether fNIRS can differentiate between automatic (i.e., not requiring one's attention) and non-automatic movement processes. Special attention was attributed to systemic artifacts (i.e., changes in blood pressure, heart rate, breathing) which were assessed and corrected by short channels, i.e., fNIRS channels which are mainly sensitive to superficial scalp hemodynamics. Twenty-three seated, healthy participants tapped four fingers on a keyboard or tapped the right foot on four squares on the floor in a specific order given by a 12-digit sequence (e.g., 434141243212). Two different sequences were executed: a beforehand learned (i.e., automatic) version and a newly learned (i.e., non-automatic) version. A 36-channel fNIRS device including 12 short channels covered multiple motor-related cortical areas including M1. The fNIRS data were analyzed with a general linear model (GLM). Correlation between the expected functional hemodynamic responses (i.e. task regressor) and the short channels (i.e. nuisance regressors), necessitated performing a separate short channel regression instead of integrating them in the GLM. Consistent with the M1 somatotopy, we found significant HbO increases of very large effect size in the lateral M1 channels during finger tapping (Cohen's d = 1.35, p <0.001) and significant HbO increases of moderate effect size in the medial M1 channels during foot tapping (Cohen's d = 0.8, p <0.05). The cortical activity differences between automatic and non-automatic tasks were not significantly different. Importantly, leg movements produced large systemic fluctuations, which were adequately removed by the use of all available short channels. Our results indicate that fNIRS is sensitive to leg activity in M1, though the sensitivity is lower than for finger activity and requires rigorous correction for systemic fluctuations. We furthermore highlight that systemic artifacts may result in an unreliable GLM analysis when short channels show signals that are similar to the expected hemodynamic responses. [ABSTRACT FROM AUTHOR]

Task preparation has been associated with a transient suppression of corticospinal excitability (CSE) before target onset, but it is an open question to what extent CSE suppression during task preparation is susceptible to motivational factors. Here, we examined whether CSE suppression is modulated by reward anticipation, and, if so, how this modulation develops over time. We administered a cue-target delay paradigm in which 1000 ms before target onset a cue was presented indicating whether or not reward could be obtained for fast and accurate responses in a Simon task. Single-pulse transcranial magnetic stimulation was applied over left primary motor cortex (M1) during the delay period (400, 600, or 800 ms after cue onset) or 200 ms after target onset, and electromyography was obtained from the right first dorsal interosseous muscle. Behaviorally, the anticipation of reward improved performance (i.e. faster reaction times). Most importantly, during reward anticipation we observed a linear decrease of motor evoked potential amplitudes that was absent when no reward was anticipated. This suggests that reward anticipation modulates CSE during task preparation. [ABSTRACT FROM AUTHOR]

Oscillatory activity in the beta range, in human primary motor cortex (M1), shows interesting dynamics that are tied to behaviour and change systematically in disease. To investigate the pathophysiology underlying these changes, we must first understand how changes in beta activity are caused in healthy subjects. We therefore adapted a canonical (repeatable) microcircuit model used in dynamic causal modelling (DCM) previously used to model induced responses in visual cortex. We adapted this model to accommodate cytoarchitectural differences between visual and motor cortex. Using biologically plausible connections, we used Bayesian model selection to identify the best model of measured MEG data from 11 young healthy participants, performing a simple handgrip task. We found that the canonical M1 model had substantially more model evidence than the generic canonical microcircuit model when explaining measured MEG data. The canonical M1 model reproduced measured dynamics in humans at rest, in a manner consistent with equivalent studies performed in mice. Furthermore, the changes in excitability (self-inhibition) necessary to explain beta suppression during handgrip were consistent with the attenuation of sensory precision implied by predictive coding. These results establish the face validity of a model that can be used to explore the laminar interactions that underlie beta-oscillatory dynamics in humans in vivo . Our canonical M1 model may be useful for characterising the synaptic mechanisms that mediate pathophysiological beta dynamics associated with movement disorders, such as stroke or Parkinson's disease. [ABSTRACT FROM AUTHOR]

Sophisticated tongue movements contribute to speech and mastication. These movements are regulated by communication between the bilateral cortex and each tongue side. The functional connection between the cortex and tongue was investigated using oscillatory interactions between whole-head magnetoencephalographic (MEG) signals and electromyographic (EMG) signals from both tongue sides during human tongue protrusion compared to thumb data. MEG–EMG coherence was observed at 14–36 Hz and 2–10 Hz over both hemispheres for each tongue side. EMG–EMG coherence between tongue sides was also detected at the same frequency bands. Thumb coherence was detected at 15–33 Hz over the contralateral hemisphere. Tongue coherence at 14–36 Hz was larger over the contralateral vs. ipsilateral hemisphere for both tongue sides. Tongue cortical sources were located in the lower part of the central sulcus and were anterior and inferior to the thumb areas, agreeing with the classical homunculus. Cross-correlogram analysis showed the MEG signal preceded the EMG signal. The cortex–tongue time lag was shorter than the cortex–thumb time lag. The cortex–muscle time lag decreased systematically with distance. These results suggest that during tongue protrusions, descending motor commands are modulated by bilateral cortical oscillations, and each tongue side is dominated by the contralateral hemisphere. [ABSTRACT FROM AUTHOR]

Abstract: Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA approved use. While TMS alone is able to up- (or down-) regulate a targeted neural system, we argue that TMS applied as an adjuvant is more effective for repetitive physical, behavioral and cognitive therapies, that is, therapies which are designed to alter the network properties of neural systems through Hebbian learning. We tested this hypothesis in the context of a slow motor learning paradigm. Healthy right-handed individuals were assigned to receive 5Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor cortex (M1) as they performed daily motor practice of a digit sequence task with their non-dominant hand for 4weeks. Resting cerebral blood flow (CBF) was measured by H2 15O PET at baseline and after 4weeks of practice. Sequence performance was measured daily as the number of correct sequences performed, and modeled using a hyperbolic function. Sequence performance increased significantly at 4weeks relative to baseline in both groups. The TMS group had a significant additional improvement in performance, specifically, in the rate of skill acquisition. In both groups, an improvement in sequence timing and transfer of skills to non-trained motor domains was also found. Compared to the sham group, the TMS group demonstrated increases in resting CBF specifically in regions known to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus, and cerebellum. These results indicate that TMS applied concomitantly augments behavioral effects of motor practice, with corresponding neural plasticity in motor sequence learning network. These findings are the first demonstration of the behavioral and neural enhancing effects of TMS on slow motor practice and have direct application in neurorehabilitation where TMS could be applied in conjunction with physical therapy. [Copyright &y& Elsevier]

Abstract: How do populations of neurons represent a variable of interest? The notion of feature spaces is a useful concept to approach this question: According to this model, the activation patterns across a neuronal population are composed of different pattern components. The strength of each of these components varies with one latent feature, which together are the dimensions along which the population represents the variable. Here we propose a new method to determine the number of feature dimensions that best describes the activation patterns. The method is based on Gaussian linear classifiers that use only the first d most important pattern dimensions. Using cross-validation, we can identify the classifier that best matches the dimensionality of the neuronal representation. We test this method on two datasets of motor cortical activation patterns measured with functional magnetic resonance imaging (fMRI), during (i) simultaneous presses of all fingers of a hand at different force levels and (ii) presses of different individual fingers at a single force level. As expected, the new method shows that the representation of force is low-dimensional; the neural activation for different force levels is scaled versions of each other. In comparison, individual finger presses are represented in a full, four-dimensional feature space. The approach can be used to determine an important characteristic of neuronal population codes without knowing the form of the underlying features. It therefore provides a novel tool in the building of quantitative models of neuronal population activity as measured with fMRI or other approaches. [Copyright &y& Elsevier]

Abstract: To find out in which detail the kinematics of observed movements is represented in the viewer''s brain, we searched for brain areas displaying coherent magnetoencephalographic (MEG) activity with observed repetitive hand movements. Whole-scalp MEG signals were recorded from 10 right-handed young adults who observed repetitive 3-Hz right-hand flexion–extension movements performed by the experimenter. The coherence between the subject''s MEG signals and the experimenter''s index-finger acceleration was computed to index the level of actor–observer coupling. The underlying cortical activity was identified with Dynamic Imaging of Coherent Sources. In all subjects, coherence spectra showed statistically significant peaks at movement frequency (F0) and its first harmonic (F1), strongest at visual areas. At F0, additional significant local coherence maxima, clearly distinct from the coherent visual areas, occurred in the primary motor (M1) cortices of both hemispheres and in the cerebellum (posterior vermis and hemispheres). Our results highlight the time-sensitive involvement of the M1 cortices and cerebellum in the kinematic representation of observed repetitive, non-goal directed motor actions. [Copyright &y& Elsevier]

Abstract: The dorsal premotor cortex (PMd) plays an import role in action control, sensorimotor integration and motor recovery. Animal studies and human data have demonstrated direct connections between ipsilateral PMd and primary motor cortex hand area (M1HAND). In this study we adopted a multimodal approach combining highly focal dual-site TMS (dsTMS) and diffusion tensor imaging (DTI) to probe ipsilateral effective and structural connectivity between PMd and M1HAND in humans. A suprathreshold test stimulus (TS) was applied to left M1HAND producing a motor evoked potential (MEP) and a subsequent conditioning stimulus (CS) to ipsilateral rostromedial PMd at short latencies ranging from of 0.8 to 2.0ms. At an interstimulus interval of 1.2ms, dsTMS of the left M1HAND and PMd facilitated MEP amplitudes relative to unconditioned TMS of M1HAND. This PMd to M1HAND facilitation was absent during voluntary contraction of the target muscle. During a two-choice reaction time task, PMd–M1HAND facilitation was only observed when dsTMS was given 125ms after presentation of the cue and subjects responded with their right hand, but not for left hand responses. Our results reveal a short-latency PMd to M1HAND connection which modulates excitability of ipsilateral M1HAND in a task and effector specific manner. DTI revealed that individual increases in PMd to M1HAND facilitation were correlated with fractional anisotropy and axial diffusivity in the juxtacortical white matter underlying the caudal portion of the left superior frontal gyrus. This finding shows that the functional strength of this connection from medial PMd to M1HAND has a microstructural correlate in the underlying subcortical white matter. This novel dsTMS paradigm can be used to non-invasively probe effective PMd to M1HAND connectivity in healthy individuals and patients with impaired hand function. [Copyright &y& Elsevier]

Abstract: Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a “local virtual lesion” which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level. [Copyright &y& Elsevier]

Abstract: Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain–computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROIm) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROIm fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROIm during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROIm during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system. [Copyright &y& Elsevier]

Abstract: We utilized a sulcus-based computational approach to investigate the relationship between the three-dimensional (3D) morphology of the central sulcus (CS) and age. The anterior and posterior walls of the CS were manually outlined using high-resolution magnetic resonance images of 295 right-handed healthy participants (age range: 18~94years). Surface reconstruction and parameterization methods were employed to create anatomical correspondence of surface locations across participants. Four surface metrics, including average sulcal length (SL), surface area, fractal dimension (FD) and sulcal span, were used to represent the 3D morphology of the CS. We found significant age-related decreases in the surface area for all walls of the CS, the SL for posterior walls of the CS and the FD for posterior wall of right CS. Age-related increases were found in the sulcal spans between the anterior and posterior walls. These surface metrics (except FD) exhibited leftward asymmetries. Specifically, age-related changes in surface morphology progressed more rapidly in the posterior than in the anterior walls. Finally, sex differences were found only in the FD of the right anterior wall of the CS. Taken together, our results show age-related changes in the surface morphology of the CS and therefore provide insights into the normal aging process. [Copyright &y& Elsevier]

Abstract: We present a novel method, corticokinematic coherence (CKC), for functional mapping of the motor cortex by computing coherence between cortical magnetoencephalographic (MEG) signals and the kinematics of voluntary movements. Ten subjects performed self-paced flexion–extensions of the right-hand fingers at about 3Hz, with a three-axis accelerometer attached to the index finger. Cross-correlogram and coherence spectra were computed between 306 MEG channels and the accelerometer signals. In all subjects, accelerometer and coherence spectra showed peaks around 3–5Hz and 6–10Hz, corresponding to the movement frequencies. The coherence was statistically significant (P <0.05) in all subjects, with sources at the hand area of the primary motor cortex contralateral to the movement. CKC appears to be a promising and robust method for reliable and convenient functional mapping of the human motor cortex. [Copyright &y& Elsevier]

Abstract: Hand motor tasks are frequently used to assess impaired motor function in neurology and neurorehabilitation. Assessments can be varied by means of hand laterality, i.e. unimanual or bimanual performance, as well as by means of task complexity, i.e. different degrees ranging from simple to complex sequence tasks. The resulting functional activation in human primary motor cortex (M1) has been studied intensively by traditional neuroimaging methods. Previous studies using functional near-infrared spectroscopy (fNIRS) investigated simple hand motor tasks. However, it is unknown whether fNIRS can also detect changes in response to increasing task complexity. Our hypothesis was to show that fNIRS could detect activation changes in relation to task complexity in uni- and bimanual tasks. Sixteen healthy right-handed subjects performed five finger-tapping tasks: unimanual left and right, simple and complex tasks as well as bimanual complex tasks. We found significant differences in oxy-hemoglobin (O2Hb) and deoxy-hemoglobin (HHb) concentration in the right hemisphere over M1. Largest O2Hb concentration changes were found during complex (0.351±0.051 μmol/l) and simple (0.275±0.054 μmol/l) right hand tasks followed by bimanual (0.249±0.047 μmol/l), complex (0.154±0.034 μmol/l) and simple (0.110±0.034 μmol/l) left hand tasks. Largest HHb concentration changes were found during bimanual (−0.138±0.006 μmol/l) tasks, followed by simple right hand (−0.12±0.016 μmol/l), complex left (−0.0875±0.007 μmol/l), complex right (−0.0863±0.005 μmol/l) and simple left (−0.0674±0.005 μmol/l) hand tasks. We report for the first time that fNIRS detects oxygenation changes in relation to task complexity during finger-tapping. The study aims to contribute to the establishment of fNIRS as a neuroimaging method to assess hand motor function in clinical settings where traditional neuroimaging methods cannot be applied. [Copyright &y& Elsevier]

Abstract: Unilateral voluntary movements are accompanied by robust activation of contralateral primary motor cortex (M1) in a somatotopic fashion. Occasionally, coactivation of M1 (M1-CoA) ipsilateral to the movement was described. In a study with brain tumor patients, we consistently observed additional somatotopic M1-CoAs and hypothesized that they might represent a basic feature of movement execution. To test this hypothesis, we used BOLD functional magnetic resonance imaging in healthy subjects and show that unilateral voluntary movements of the fingers or toes go along not only with contralateral M1 activation, but also with ipsilateral M1-CoA of the respective homotopic representation and bilateral M1-CoA of different heterotopic representations not directly involved in the executed movement. Moreover, bilateral M1-CoA of heterotopic representations was observed in tongue movements. All M1-CoAs respected the correct somatotopy; however, their Euclidean coordinates were shifted and resembled to those obtained for imagined movements rather than for actual movements. BOLD signal intensities and correlations to the applied hemodynamic reference function were lower in M1-CoAs as compared to the M1 activations driving the movement but did not differ between homo- and heterotopic M1-CoAs. Thus, we propose that specific unilateral voluntary movements are accompanied by a global activation of primary motor areas, reflecting an overall increase in neuronal activity and unraveling the fundamental principle of distributed processing in M1. Executive motor function may rely on a balance of inhibitory and excitatory neuronal activity, where actual movement would result from a shift towards excitation. [Copyright &y& Elsevier]

Abstract: Many studies measured cerebral blood flow changes in the stimulated primary motor cortex during repetitive transcranial magnetic stimulation (rTMS) using PET, SPECT, and fMRI; however, most of these procedures are associated with problems related to temporal resolution and magnetic field artifacts that are produced by rTMS. In this study of 12 healthy right-handed volunteers, we measured the hemoglobin (Hb) concentration change in the stimulated primary motor cortex during and after rTMS using rTMS coil and near infrared spectroscopy (NIRS) with high temporal sampling (every 125 ms). The left primary motor cortex that controls the right first dorsal interosseus (FDI) muscle was stimulated 10 times with an angle figure-of-eight coil at a frequency of 0.5 or 2 Hz, at intensity of 80% or 120% of resting motor threshold (RMT). We used 4 stimulus conditions: (1) 2 Hz-120% RMT, (2) 2 Hz-80% RMT, (3) 0.5 Hz-120% RMT, and (4) 0.5 Hz-80% RMT. We observed small intensity-dependent increments in total- and oxy-Hb concentrations around 5 s at the 120% RMT condition. Greater decrements in total- and oxy-Hb concentrations and increment of deoxy-Hb concentration were observed during and after rTMS at all conditions, both at the supra-threshold and sub-threshold stimulus intensities. Our results emphasize the suitability of NIRS combined with rTMS for detecting changes in cerebral blood flow. [Copyright &y& Elsevier]

Abstract: Several tracing studies have established a topographical distribution of fiber connections to the cortex in midsagittal cross-sections of the corpus callosum (CC). The most prominent example is Witelson''s scheme, which defines five vertical partitions mainly based on primate data. Conventional MRI of the human CC does not reveal morphologically discernable structures, although microscopy techniques identified myelinated axons with a relatively small diameter in the anterior and posterior third of the CC as opposed to thick fibers in the midbody and posterior splenium. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to gain cortical connectivity information of the CC in individual subjects. With DTI-based tractography, we distinguished five vertical segments of the CC, containing fibers projecting into prefrontal, premotor (and supplementary motor), primary motor, and primary sensory areas as well as into parietal, temporal, and occipital cortical areas. Striking differences to Witelson''s classification were recognized in the midbody and anterior third of the CC. In particular, callosal motor fiber bundles were found to cross the CC in a much more posterior location than previously indicated. Differences in water mobility were found to be in qualitative agreement with differences in the microstructure of transcallosal fibers yielding the highest anisotropy in posterior regions of the CC. The lowest anisotropy was observed in compartments assigned to motor and sensory cortical areas. In conclusion, DTI-based fiber tractography of healthy human subjects suggests a modification of the widely accepted Witelson scheme and a new classification of vertical CC partitions. [Copyright &y& Elsevier]

Abstract: The mesial premotor cortex (pre-supplementary motor area and supplementary motor area proper), lateral premotor cortex (dorsal premotor cortex and ventral premotor cortex), and primary sensorimotor cortex (primary motor cortex and primary somatosensory cortex) have been identified as key cortical areas for sensorimotor function. However, the three-dimensional (3-D) anatomic boundaries between these regions remain unclear. In order to clarify the locations and boundaries for these six sensorimotor regions, we surveyed 126 articles describing pre-supplementary motor area, supplementary motor area proper, dorsal premotor cortex, ventral premotor cortex, primary motor cortex, and primary somatosensory cortex. Using strict inclusion criteria, we recorded the reported normalized stereotaxic coordinates (Talairach and Tournoux or MNI) from each experiment. We then computed the probability distributions describing the likelihood of activation, and characterized the shape, extent, and area of each sensorimotor region in 3-D. Additionally, we evaluated the nature of the overlap between the six sensorimotor regions. Using the findings from this meta-analysis, along with suggestions and guidelines of previous researchers, we developed the Human Motor Area Template (HMAT) that can be used for ROI analysis. HMAT is available through e-mail from the corresponding author. [Copyright &y& Elsevier]

Abstract: While several recent imaging studies confirm that motor foot areas can still be activated in complete and chronic paraplegia, it remains unclear whether their functionality is also maintained or declines after years of “non-use”. Force control is one of the most important and best investigated functions within the motor cortex. It has been repeatedly reported that the motor cortex is more active when higher forces have to be applied. We thus addressed the question of preserved cortical functions by comparing motor force control patterns in the event-related potentials of 10 motor complete paraplegic subjects and 10 controls after attempted (paraplegic patients)/executed (healthy controls) ballistic foot movements with three different force levels. In addition to the peak amplitudes reflecting force levels, peak latencies were also investigated to elucidate timing as another functional aspect of motor control. No significant group difference was found for the peak latencies, indicating that the timing of motor cortical activation is preserved. Concerning amplitudes, we found preserved cortical modulation of higher forces but distorted low force modulation, especially early after injury. These findings thus suggest that important aspects of cortical control over paralyzed limbs are maintained despite years of “non-use”. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Repetitive transcranial magnetic stimulation (rTMS) to the human primary motor cortex (M1) causes bidirectional changes in corticospinal excitability depending on the stimulation frequency used. We used functional brain imaging to compare the effects of 5 Hz and 1 Hz-rTMS on local and inter-regional connectivity within the motor system. Regional cerebral blood flow (rCBF) was measured as a marker of synaptic activity at rest and during freely selected finger movements. We hypothesized that increased cortical excitability induced by 5 Hz-rTMS over M1 has an opposite effect on the synaptic activity and the connectivity of the motor network from the decreased cortical excitability induced by 1 Hz-rTMS. rTMS at both frequencies induced similar changes in rCBF at the site of stimulation and within areas of the motor network engaged by the task. The two frequencies showed different effects on movement-related coupling between motor areas. Connectivity analyses also indicated a differential effect of 5 and 1 Hz-rTMS on motor network connectivity, suggesting a role for an inferomedial portion of left M1 and left dorsal premotor cortex in maintaining performance. These results suggest that rapid reorganization of the motor system occurs to maintain task performance during periods of altered cortical excitability. This reorganization differs according to the modulation of excitability which is a function of rTMS frequency. This study extends the work of Lee et al. (Lee, L., Siebner, H.R., Rowe, J.B., Rizzo, V. Rothwell, J.C. Frackowiak, R.S. Friston, K.J., 2003. Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J. Neurosci. 23, 5308–5318.) by providing evidence that the pattern of acute reorganization in the motor network following rTMS depends on the direction of conditioning. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Spontaneous ∼20-Hz oscillations, arising predominantly from the primary motor cortex (MI), are readily observed by magnetoencephalography (MEG). Prior studies have indicated that the level of the ∼20-Hz rhythm reflects the functional state of the MI cortex: increased 20-Hz level is associated with increased inhibition and suppression of the rhythm with excitation of MI. Close interaction is suggested between pain and the motor system by the association of chronic pain with motor dysfunction and by the alleviation of pain by motor-cortex stimulation. We therefore explored the effect of noxious input on motor-cortex functions by recording MEG signals from nine healthy subjects during selective laser stimulation of Aδ- and C-fibers of the hand. The ∼20-Hz level was suppressed in the contralateral MI cortex in all nine subjects after painful Aδ- and C-fiber stimuli (P < 0.001). The suppression started 180 ± 10 ms (mean ± SEM) after Aδ-fiber stimuli and 820 ± 30 ms after C-fiber stimuli, and peaked 160–170 ms later. Similar, but about 50% weaker, suppression of the ∼20-Hz oscillations occurred in seven out of nine subjects in the ipsilateral MI. These results suggest automatic, lateralized, excitation of the MI cortex by noxious Aδ- and C-fiber input. [Copyright &y& Elsevier]

Engagement of the primary motor cortex (MI) during the observation of actions has been debated for a long time. In the present study, we used the quantitative 14C-deoxyglucose method in monkeys that either grasped 3-D objects or observed the same movements executed by humans. We found that the forelimb regions of the MI and the primary somatosensory (SI) cortex were significantly activated in both cases. Our study resolves a debate in the literature, providing strong evidence for use of MI representations during the observation of actions. It demonstrates that the observation of an action is represented in the primary motor and somatosensory cortices as is its execution. It indicates that in terms of neural correlates, recognizing a motor behavior is like executing the same behavior, requiring the involvement of a distributed system encompassing not only the premotor but also the primary motor cortex. We suggest that movements and their proprioceptive components are stored as motor and somatosensory representations in motor and somatosensory cortices, respectively, and that these representations are recalled during observation of an action. [Copyright &y& Elsevier]

Tool use is a characteristic human trait, requiring motor skills that are largely learned by imitation. A neural system that supports imitation and action understanding by directly matching observed actions and their motor counterparts has been found in the human premotor and motor cortices. To test whether this “mirror-neuron system” (MNS) would be activated by observation of tool use, we recorded neuromagnetic oscillatory activity from the primary motor cortex of 10 healthy subjects while they observed the experimenter to use chopsticks in a goal-directed and non-goal-directed manner. The left and right median nerves were stimulated alternatingly, and the poststimulus rebounds of the ∼20-Hz motor-cortex rhythms were quantified. Compared with the rest condition, the level of the ∼20-Hz rhythm was suppressed during observation of both types of tool use, indicating activation of the primary motor cortex. The suppression was on average 15–17% stronger during observation of goal-directed than non-goal-directed tool use, and this difference correlated positively with the frequency of subjects'' chopstick use during the last year. These results support the view that the motor-cortex activation is related to the observer''s ability to understand and imitate motor acts. [Copyright &y& Elsevier]

The aim of this work was to study the relevance of the primary motor cortex (M1) for motor functions different to the simple execution of motor orders. The M1 activity during the performance with individual fingers of a simple motor task (tonic flexion), a motor task that includes a complex motor computation but not motor execution (motor imagery), and a motor task that involves both the computation and execution of movements (phasic movement) was evaluated by functional magnetic resonance imaging (fMRI). The possible influence of other cortical tasks on the M1 activation induced by finger movements was assessed by evaluating the effect of a distracting concurrent task (numeric calculation). Data show that both the dimension of the area activated and the intensity of response were higher during motor planning than during motor execution. There is a mosaic-like distribution for motor-planning M1 functions, with the movement of individual fingers being controlled from several M1 loci. The concurrent mental-task induces a rapid functional reconfiguration of M1, adding M1 subsets to motor programming but excluding others. Present data support the involvement of the M1 in more than just simple motor execution, showing broader and more intense modifications during motor tasks not accompanied by movements (motor imagery) than during the execution of simple motor acts (tonic flexion). [Copyright &y& Elsevier]

There are formidable problems in studying how ‘real’ music engages the brain over wide ranges of temporal scales extending from milliseconds to a lifetime. In this work, we recorded the magnetoencephalographic signal while subjects listened to music as it unfolded over long periods of time (seconds), and we developed and applied methods to correlate the time course of the regional brain activations with the dynamic aspects of the musical sound. We showed that frontal areas generally respond with slow time constants to the music, reflecting their more integrative mode; motor-related areas showed transient-mode responses to fine temporal scale structures of the sound. The study combined novel analysis techniques designed to capture and quantify fine temporal sequencing from the authentic musical piece (characterized by a clearly defined rhythm and melodic structure) with the extraction of relevant features from the dynamics of the regional brain activations. The results demonstrated that activity in motor-related structures, specifically in lateral premotor areas, supplementary motor areas, and somatomotor areas, correlated with measures of rhythmicity derived from the music. These correlations showed distinct laterality depending on how the musical performance deviated from the strict tempo of the music score, that is, depending on the musical expression. [Copyright &y& Elsevier]