M1 Hand Area Research Articles

Correlation of bilateral M1 hand area excitability and overall functional recovery after spinal cord injury: protocol for a prospective cohort study

BackgroundAfter spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown.ObjectiveTo clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation.MethodsThis study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment.DiscussionThe present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI.Trial registration numberChiCTR2300068831.

Gray matter volume of functionally relevant primary motor cortex is causally related to learning a hand motor task.

Variability in brain structure is associated with the capacity for behavioral change. However, a causal link between specific brain areas and behavioral change (such as motor learning) has not been demonstrated. We hypothesized that greater gray matter volume of a primary motor cortex (M1) area active during a hand motor learning task is positively correlated with subsequent learning of the task, and that the disruption of this area blocks learning of the task. Healthy participants underwent structural MRI before learning a skilled hand motor task. Next, participants performed this learning task during fMRI to determine M1 areas functionally active during this task. This functional ROI was anatomically constrained with M1 boundaries to create a group-level "Active-M1" ROI used to measure gray matter volume in each participant. Greater gray matter volume in the left hemisphere Active-M1 ROI was related to greater motor learning in the corresponding right hand. When M1 hand area was disrupted with repetitive transcranial stimulation (rTMS), learning of the motor task was blocked, confirming its causal link to motor learning. Our combined imaging and rTMS approach revealed greater cortical volume in a task-relevant M1 area is causally related to learning of a hand motor task in healthy humans.

Finger-specific representations are sharpened during a fatiguing motor task

Introduction
 Motor fatigability is a limiting factor in any kind of setting, in which physical performance is required. Motor fatigability can be quantified through the decrease in movement speed, when low-force movements are performed repeatedly with maximal speed. In this study, we measure motor fatigability in healthy participants through fast finger tapping for 30s. Previous research has shown that the decrease in movement speed, also called motor slowing, is associated with a rise in brain activity, a reduction in surround inhibition in the primary sensorimotor cortex (SM1), and an increase in co-activation of antagonistic muscle groups involved in the movement (Bächinger et al., 2019). However, it remains an open question of whether motor slowing and the associated release of inhibition causes a reduction of signal-to-noise ratio for movement-specific information. Here, we aim to answer this question by assessing finger representations using representational similarity analysis (RSA) when participants perform fatiguing tapping with either the index or middle finger. We hypothesized that a reduction of movement-specific information would be associated with the index and middle finger representations in SM1 getting “blurred” over time due to a gradual break-down of surround inhibition. Thus, if the signal-to-noise ratio of movement-specific information decreases in parallel with motor slowing, we would expect finger representations to become more overlapping. Vice-versa, if the signal-to-noise ratio of movement-specific information increases despite motor slowing, we would expect sharper finger representation.
 Methods
 26 healthy young participants performed a motor slowing task during functional MRI. The participants performed 30s of maximal speed finger tapping with the index and the middle finger, alternating between trials. To quantify motor slowing from the behaviour, we performed a linear regression analysis. For the first-level general linear model of the fMRI data, the fingers were regressed separately and the 30s of tapping were further split into 3 x 10s regressors (time bin 1, bin 2, bin 3). We performed RSA separately on each 10s regressor for the anatomically defined regions of interest M1 and S1 hand area (Diedrichsen et al., 2013; Walther et al., 2016) and therefore obtained a dissimilarity measure for each time bin. A mixed effects model with the factor time was used to test whether dissimilarity changed across time bins.
 Results
 On the behavioural level, motor slowing could be observed, as tapping speed significantly decreased in each finger over time (F(1, 76) >= 5.78, p <=.05). Concerning the dissimilarity measure, we found an increase over time for S1 as well as M1 (F(2, 50) >= 17.41, p <=.001).
 Discussion/Conclusion
 We conclude that the finger representations in the sensorimotor cortex become more distinct with motor slowing. This suggests that the signal-to-noise ratio of movement-specific information is increased, potentially to compensate for supraspinal changes caused by fatigability.
 References
 Bächinger, M., Lehner, R., Thomas, F., Hanimann, S., Balsters, J., & Wenderoth, N. (2019). Human motor fatigability as evoked by repetitive movements results from a gradual breakdown of surround inhibition. eLife, 8, Article e46750. https://doi.org/10.7554/eLife.46750
 Diedrichsen, J., Wiestler, T., & Krakauer, J. W. (2013). Two distinct ipsilateral cortical representations for individuated finger movements. Cerebral Cortex, 23(6), 1362–1377. https://doi.org/10.1093/cercor/bhs120
 Walther, A., Nili, H., Ejaz, N., Alink, A., Kriegeskorte, N., & Diedrichsen, J. (2016). Reliability of dissimilarity measures for multi-voxel pattern analysis. NeuroImage, 137, 188–200. https://doi.org/10.1016/j.neuroimage.2015.12.012

Primary motor hand area corticospinal excitability indicates overall functional recovery after spinal cord injury.

After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown. A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability. The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0-6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor. The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery.

Language-related motor facilitation in Italian Sign Language signers.

Linguistic tasks facilitate corticospinal excitability as revealed by increased motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in the dominant hand. This modulation of the primary motor cortex (M1) excitability may reflect the relationship between speech and gestures. It is conceivable that in healthy individuals who use a sign language this cortical excitability modulation could be rearranged. The aim of this study was to evaluate the effect of spoken language tasks on M1 excitability in a group of hearing signers. Ten hearing Italian Sign Language (LIS) signers and 16 non-signer healthy controls participated. Single-pulse TMS was applied to either M1 hand area at the baseline and during different tasks: (i) reading aloud, (ii) silent reading, (iii) oral movements, (iv) syllabic phonation and (v) looking at meaningless non-letter strings. Overall, M1 excitability during the linguistic and non-linguistic tasks was higher in LIS group compared to the control group. In LIS group, MEPs were significantly larger during reading aloud, silent reading and non-verbal oral movements, regardless the hemisphere. These results suggest that in hearing signers there is a different modulation of the functional connectivity between the speech-related brain network and the motor system.

Mapping the Integration of Sensory Information across Fingers in Human Sensorimotor Cortex.

The integration of somatosensory signals across fingers is essential for dexterous object manipulation. Previous experiments suggest that this integration occurs in neural populations in the primary somatosensory cortex (S1). However, the integration process has not been fully characterized, as previous studies have mainly used 2-finger stimulation paradigms. Here, we addressed this gap by stimulating all 31 single- and multifinger combinations. We measured population-wide activity patterns evoked during finger stimulation in human S1 and primary motor cortex (M1) using 7T fMRI in female and male participants. Using multivariate fMRI analyses, we found clear evidence of unique nonlinear interactions between fingers. In Brodmann area (BA) 3b, interactions predominantly occurred between pairs of neighboring fingers. In BA 2, however, we found equally strong interactions between spatially distant fingers, as well as interactions between finger triplets and quadruplets. We additionally observed strong interactions in the hand area of M1. In both M1 and S1, these nonlinear interactions did not reflect a general suppression of overall activity, suggesting instead that the interactions we observed reflect rich, nonlinear integration of sensory inputs from the fingers. We suggest that this nonlinear finger integration allows for a highly flexible mapping from finger sensory inputs to motor responses that facilitates dexterous object manipulation.SIGNIFICANCE STATEMENT Processing of somatosensory information in primary somatosensory cortex (S1) is essential for dexterous object manipulation. To successfully handle an object, the sensorimotor system needs to detect complex patterns of haptic information, which requires the nonlinear integration of sensory inputs across multiple fingers. Using multivariate fMRI analyses, we characterized brain activity patterns evoked by stimulating all single- and multifinger combinations. We report that progressively stronger multifinger interactions emerge in posterior S1 and in the primary motor cortex (M1), with interactions arising between inputs from neighboring and spatially distant fingers. Our results suggest that S1 and M1 provide the neural substrate necessary to support a flexible mapping from sensory inputs to motor responses of the hand.

Speech motor facilitation is not affected by ageing but is modulated by task demands during speech perception

Motor areas for speech production activate during speech perception. Such activation may assist speech perception in challenging listening conditions. It is not known how ageing affects the recruitment of articulatory motor cortex during active speech perception. This study aimed to determine the effect of ageing on recruitment of speech motor cortex during speech perception.Single-pulse Transcranial Magnetic Stimulation (TMS) was applied to the lip area of left primary motor cortex (M1) to elicit lip Motor Evoked Potentials (MEPs). The M1 hand area was tested as a control site. TMS was applied whilst participants perceived syllables presented with noise (−10, 0, +10 dB SNRs) and without noise (clear). Participants detected and counted syllables throughout MEP recording. Twenty younger adult subjects (aged 18–25) and twenty older adult subjects (aged 65–78) participated in this study.Results indicated a significant interaction between age and noise condition in the syllable task. Specifically, older adults significantly misidentified syllables in the 0 dB SNR condition, and missed the syllables in the −10 dB SNR condition, relative to the clear condition. There were no differences between conditions for younger adults. There was a significant main effect of noise level on lip MEPs. Lip MEPs were unexpectedly inhibited in the 0 dB SNR condition relative to clear condition. There was no interaction between age group and noise condition. There was no main effect of noise or age group on control hand MEPs. These data suggest that speech-induced facilitation in articulatory motor cortex is abolished when performing a challenging secondary task, irrespective of age.

Bihemispheric sensorimotor oscillatory network states determine cortical responses to transcranial magnetic stimulation

BackgroundBrain responses to external stimuli vary with fluctuating states of neuronal activity. Previous work has demonstrated effects of phase and power of the ongoing local sensorimotor μ-alpha-oscillation on responses to transcranial magnetic stimulation (TMS) of motor cortex (M1). However, M1 is part of a distributed network, and the effects of oscillatory activity in this network on TMS-evoked EEG responses (TEPs) have not been explored. ObjectivesTo determine the effects of oscillatory activity in the bihemispheric sensorimotor network on TEPs. Methods31 healthy subjects received single-pulse TMS of the left M1 hand area during EEG recording. Ongoing bihemispheric sensorimotor cortex oscillatory states were reconstructed from the EEG directly preceding TMS, and inferred by a data-driven method combining a multivariate autoregressive model and a Hidden Markov model. TEP amplitudes (P25, N45, P70, N100 and P180) were then compared between different bihemispheric sensorimotor cortex oscillatory states. ResultsFour bihemispheric sensorimotor cortex oscillatory states were identified, with different interhemispheric expressions of theta and alpha oscillations. High alpha-power states in the stimulated sensorimotor cortex increased P25 amplitude. Alpha power in the alpha-alpha state (stimulated - non-stimulated hemisphere) correlated in both hemispheres with N45 amplitude. Theta power in the alpha-theta state correlated in the non-stimulated hemisphere with P70 amplitude. ConclusionsBihemispheric sensorimotor cortex oscillatory states contribute to TEPs, with a relevance shift from stimulated to non-stimulated M1 from P25 over N45 to P70. This significantly extends previous findings: not only ongoing local oscillations but distributed network oscillatory states determine cortical responsiveness to external stimuli.

Degree of improving TMS focality through a geometrically stable solution of an inverse TMS problem

The Transcranial Magnetic Stimulation (TMS) inverse problem (TMS-IP) investigated in this study aims to focus the TMS induced electric field close to a specified target point defined on the gray matter interface in the M1HAND area while otherwise minimizing it. The goal of the study is to numerically evaluate the degree of improvement of the TMS-IP solutions relative to the well-known sulcus-aligned mapping (a projection approach with the 90∘ local sulcal angle). In total, 1536 individual TMS-IP solutions have been analyzed for multiple target points and multiple subjects using the boundary element fast multipole method (BEM-FMM) as the forward solver.Our results show that the optimal TMS inverse-problem solutions improve the focality – reduce the size of the field “hot spot” and its deviation from the target – by approximately 21–33% on average for all considered subjects, all observation points, two distinct coil types, two segmentation types, two intracortical observation surfaces under study, and three tested values of the field threshold. The inverse-problem solutions with the maximized focality simultaneously improve the TMS mapping resolution (differentiation between neighbor targets separated by approximately 10 mm) although this improvement is quite modest.Coil position/orientation and conductivity uncertainties have been included into consideration as the corresponding de-focalization factors. The present results will change when the levels of uncertainties change. Our results also indicate that the accuracy of the head segmentation critically influences the expected TMS-IP performance.

Neural Dynamics in Primate Cortex during Exposure to Subanesthetic Concentrations of Nitrous Oxide.

Nitrous oxide (N2O) is a hypnotic gas with antidepressant and psychedelic properties at subanesthetic concentrations. Despite long-standing clinical use, there is insufficient understanding of its effect on neural dynamics and cortical processing, which is important for mechanistic understanding of its therapeutic effects. We administered subanesthetic (70%), inhaled N2O and studied the dynamic changes of spiking rate, spectral content, and somatosensory information representation in primary motor cortex (M1) in two male rhesus macaques implanted with Utah microelectrode arrays in the hand area of M1. The average sorted multiunit spiking rate in M1 increased from 8.1 ± 0.99 to 10.6 ± 1.3 Hz in Monkey W (p < 0.001) and from 5.6 ± 0.87 to 7.0 ± 1.1 Hz in Monkey N (p = 0.003). Power spectral densities increased in beta- and gamma-band power. To evaluate somatosensory content in M1 as a surrogate of information transfer, fingers were lightly brushed and classified using a naive Bayes classifier. In both monkeys, the proportion of correctly classified fingers dropped from 0.50 ± 0.06 before N2O inhalation to 0.34 ± 0.03 during N2O inhalation (p = 0.018), although some fingers continued to be correctly classified (p = 0.005). The decrease in correct classifications corresponded to decreased modulation depth for the population (p = 0.005) and fewer modulated units (p = 0.046). However, the increased single-unit firing rate was not correlated with its modulation depth (R2 < 0.001, p = 0.93). These data suggest that N2O degrades information transfer, although no clear relationship was found between neuronal tuning and N2O-induced changes in firing rate.

Priming Effects of Water Immersion on Paired Associative Stimulation-Induced Neural Plasticity in the Primary Motor Cortex.

We aimed to verify whether indirect-wave (I-wave) recruitment and cortical inhibition can regulate or predict the plastic response to paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), and also whether water immersion (WI) can facilitate the subsequent PAS25-induced plasticity. To address the first question, we applied transcranial magnetic stimulation (TMS) to the M1 hand area, while alternating the direction of the induced current between posterior-to-anterior and anterior-to-posterior to activate two independent synaptic inputs to the corticospinal neurons. Moreover, we used a paired stimulation paradigm to evaluate the short-latency afferent inhibition (SAI) and short-interval intracortical inhibition (SICI). To address the second question, we examined the motor evoked potential (MEP) amplitudes before and after PAS25, with and without WI, and used the SAI, SICI, and MEP recruitment curves to determine the mechanism underlying priming by WI on PAS25. We demonstrated that SAI, with an inter-stimulus interval of 25 ms, might serve as a predictor of the response to PAS25, whereas I-wave recruitment evaluated by the MEP latency difference was not predictive of the PAS25 response, and found that 15 min WI prior to PAS25 facilitated long-term potentiation (LTP)-like plasticity due to a homeostatic increase in cholinergic activity.

Acute Low-Intensity Aerobic Exercise Modulates Intracortical Inhibitory and Excitatory Circuits in an Exercised and a Non-exercised Muscle in the Primary Motor Cortex.

Recent studies have reported that acute aerobic exercise modulates intracortical excitability in the primary motor cortex (M1). However, whether acute low-intensity aerobic exercise can also modulate M1 intracortical excitability, particularly intracortical excitatory circuits, remains unclear. In addition, no previous studies have investigated the effect of acute aerobic exercise on short-latency afferent inhibition (SAI). The aim of this study was to investigate whether acute low-intensity aerobic exercise modulates intracortical circuits in the M1 hand and leg areas. Intracortical excitability of M1 (Experiments 1, 2) and spinal excitability (Experiment 3) were measured before and after acute low-intensity aerobic exercise. In Experiment 3, skin temperature was also measured throughout the experiment. Transcranial magnetic stimulation was applied over the M1 non-exercised hand and exercised leg areas in Experiments 1, 2, respectively. Participants performed 30 min of low-intensity pedaling exercise or rested while sitting on the ergometer. Short- and long-interval intracortical inhibition (SICI and LICI), and SAI were measured to assess M1 inhibitory circuits. Intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) were measured to assess M1 excitatory circuits. We found that acute low-intensity aerobic exercise decreased SICI and SAI in the M1 hand and leg areas. After exercise, ICF in the M1 hand area was lower than in the control experiment, but was not significantly different to baseline. The single motor-evoked potential, resting motor threshold, LICI, SICF, and spinal excitability did not change following exercise. In conclusion, acute low-intensity pedaling modulates M1 intracortical circuits of both exercised and non-exercised areas, without affecting corticospinal and spinal excitability.

Assessment of the effect of continuous theta burst stimulation of the motor cortex on manual dexterity in non-human primates in a direct comparison with invasive intracortical pharmacological inactivation.

Non-invasive reversible perturbation techniques of brain output such as continuous theta burst stimulation (cTBS), commonly used to modulate cortical excitability in humans, allow investigation of possible roles in functional recovery played by distinct intact cortical areas following stroke. To evaluate the potential of cTBS, the behavioural effects of this non-invasive transient perturbation of the hand representation of the primary motor cortex (M1) in non-human primates (two adult macaques) were compared with an invasive focal transient inactivation based on intracortical microinfusion of GABA-A agonist muscimol. The effects on the contralateral arm produced by cTBS or muscimol were directly compared based on a manual dexterity task performed by the monkeys, the "reach and grasp" drawer task, allowing quantitative assessment of the grip force produced between the thumb and index finger and exerted on the drawer's knob. cTBS only induced modest to moderate behavioural effects, with substantial variability on manual dexterity whereas the intracortical muscimol microinfusion completely impaired manual dexterity, producing a strong and clear cortical inhibition of the M1 hand area. In contrast, cTBS induced mixed inhibitory and facilitatory/excitatory perturbations of M1, though with predominant inhibition. Although cTBS impacted on manual dexterity, its effects appear too limited and variable in order to use it as a reliable proof of cortical vicariation mechanism (cortical area replacing another one) underlying functional recovery following a cortical lesion in the motor control domain, in contrast to potent pharmacological block generated by muscimol infusion, whose application is though limited to an animal model such as non-human primate.

Interleaving Motor Sequence Training With High-Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Consolidation.

The acquisition of novel motor skills is a fundamental process of lifelong learning and crucial for everyday behavior. Performance gains acquired by training undergo a transition from an initially labile state to a state that is progressively robust towards interference, a phenomenon referred to as motor consolidation. Previous work has demonstrated that the primary motor cortex (M1) is a neural key region for motor consolidation. However, it remains unknown whether physiological processes underlying posttraining motor consolidation in M1 are active already during an ongoing training phase or only after completion of the training. We examined whether 10-Hz interleaved repetitive transcranial magnetic stimulation (i-rTMS) of M1 during rest periods between active motor training in an explicit motor learning task affects posttraining offline consolidation. Relative to i-rTMS to the vertex (control region), i-rTMS to the M1hand area of the nondominant hand facilitated posttraining consolidation assessed 6 h after training without affecting training performance. This facilitatory effect generalized to delayed performance of the mirror-symmetric sequence with the untrained (dominant) hand. These findings indicate that posttraining consolidation can be facilitated independently from training-induced performance increments and suggest that consolidation is initiated already during offline processing in short rest periods between active training phases.

Corticotectal Projections From the Premotor or Primary Motor Cortex After Cortical Lesion or Parkinsonian Symptoms in Adult Macaque Monkeys: A Pilot Tracing Study.

The corticotectal projections, together with the corticobulbar (corticoreticular) projections, work in parallel with the corticospinal tract (CST) to influence motoneurons in the spinal cord both directly and indirectly via the brainstem descending pathways. The tectospinal tract (TST) originates in the deep layers of the superior colliculus. In the present study, we analyzed the corticotectal projections from two motor cortical areas, namely the premotor cortex (PM) and the primary motor cortex (M1) in eight macaque monkeys subjected to either a cortical lesion of the hand area in M1 (n = 4) or Parkinson’s disease-like symptoms PD (n = 4). A subgroup of monkeys with cortical lesion was subjected to anti-Nogo-A antibody treatment whereas all PD monkeys were transplanted with Autologous Neural Cell Ecosystems (ANCEs). The anterograde tracer BDA was used to label the axonal boutons both en passant and terminaux in the ipsilateral superior colliculus. Individual axonal boutons were charted in the different layers of the superior colliculus. In intact animals, we previously observed that corticotectal projections were denser when originating from PM than from M1. In the present M1 lesioned monkeys, as compared to intact ones the corticotectal projection originating from PM was decreased when treated with anti-Nogo-A antibody but not in untreated monkeys. In PD-like symptoms’ monkeys, on the other hand, there was no consistent change affecting the corticotectal projection as compared to intact monkeys. The present pilot study overall suggests that the corticotectal projection is less affected by M1 lesion or PD symptoms than the corticoreticular projection previously reported in the same animals.

Can electric fields explain inter-individual variability in transcranial direct current stimulation of the motor cortex?

The effects of transcranial direct current stimulation (tDCS) on motor cortical excitability are highly variable between individuals. Inter-individual differences in the electric fields generated in the brain by tDCS might play a role in the variability. Here, we explored whether these fields are related to excitability changes following anodal tDCS of the primary motor cortex (M1). Motor evoked potentials (MEPs) were measured in 28 healthy subjects before and after 20 min sham or 1 mA anodal tDCS of right M1 in a double-blind crossover design. The electric fields were individually modelled based on magnetic resonance images. Statistical analysis indicated that the variability in the MEPs could be partly explained by the electric fields, subjects with the weakest and strongest fields tending to produce opposite changes in excitability. To explain the findings, we hypothesized that the likely locus of action was in the hand area of M1, and the effective electric field component was that in the direction normal to the cortical surface. Our results demonstrate that a large part of inter-individual variability in tDCS may be due to differences in the electric fields. If this is the case, electric field dosimetry could be useful for controlling the neuroplastic effects of tDCS.

Hand perceptions induced by single pulse transcranial magnetic stimulation over the primary motor cortex

BackgroundWhen single pulse transcranial magnetic stimulation (TMS) is applied over the primary motor cortex (M1) with sufficient intensity, it evokes muscular contractions (motor-evoked potentials, MEPs) and muscle twitches (TMS-evoked movements). Participants may also report various hand sensations related to TMS, but the perception elicited by TMS and its relationship to MEPs and evoked movements has not been systematically studied. ObjectiveThe main aim of this work is to evaluate participants' kinesthetic and somatosensory hand perceptions elicited by single-pulse TMS over M1-hand area at different intensities of stimulation and their relation with MEPs and TMS-evoked movements. MethodsWe compared the number of MEPs (measured by electromyography), TMS-evoked movements (measured by an accelerometer) and participants' hand perception (measured by verbal report) elicited by TMS at different intensity of stimulation. This way, we estimated the amplitude of MEPs and the acceleration of TMS-evoked movements sufficient to trigger TMS evoked hand perceptions. ResultsWe found that TMS-evoked hand perceptions are induced at 105% of the individual resting motor threshold, a value significantly different from the threshold inducing MEPs (about 100%) and TMS-evoked movements (about 110%). Our data indicate that only MEPs with an amplitude higher than 0.62 mV and TMS-evoked movements with acceleration higher than 0.42 m/s2 were associated with hand perceptions at threshold. ConclusionsOur data reveal the main features of TMS-evoked hand perception and show that in addition to MEPs and TMS-evoked movements, this is a separate discernible response associated to single-pulse TMS over M1.

Locating primary somatosensory cortex in human brain stimulation studies: systematic review and meta-analytic evidence.

Transcranial magnetic stimulation (TMS) over human primary somatosensory cortex (S1), unlike over primary motor cortex (M1), does not produce an immediate, objective output. Researchers must therefore rely on one or more indirect methods to position the TMS coil over S1. The "gold standard" method of TMS coil positioning is to use individual functional and structural magnetic resonance imaging (f/sMRI) alongside a stereotactic navigation system. In the absence of these facilities, however, one common method used to locate S1 is to find the scalp location that produces twitches in a hand muscle (e.g., the first dorsal interosseus, M1-FDI) and then move the coil posteriorly to target S1. There has been no systematic assessment of whether this commonly reported method of finding the hand area of S1 is optimal. To do this, we systematically reviewed 124 TMS studies targeting the S1 hand area and 95 fMRI studies involving passive finger and hand stimulation. Ninety-six TMS studies reported the scalp location assumed to correspond to S1-hand, which was on average 1.5-2 cm posterior to the functionally defined M1-hand area. Using our own scalp measurements combined with similar data from MRI and TMS studies of M1-hand, we provide the estimated scalp locations targeted in these TMS studies of the S1-hand. We also provide a summary of reported S1 coordinates for passive finger and hand stimulation in fMRI studies. We conclude that S1-hand is more lateral to M1-hand than assumed by the majority of TMS studies.

Asymmetric and Distant Effects of a Unilateral Lesion of the Primary Motor Cortex on the Bilateral Supplementary Motor Areas in Adult Macaque Monkeys.

A restricted lesion of the hand area in the primary motor cortex (M1) leads to a deficit of contralesional manual dexterity, followed by an incomplete functional recovery, accompanied by plastic changes in M1 itself and in other cortical areas on both hemispheres. Using the marker SMI-32 specific to pyramidal neurons in cortical layers III and V, we investigated the impact of a focal unilateral M1 lesion (hand representation) on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres in nine adult macaque monkeys compared with four intact control monkeys. The M1 lesion induced a consistent interhemispheric asymmetry in density of SMI-32-positive neurons in F3 layer V (statistically significant in 8 of 9 lesioned monkeys), highly correlated with the lesion volume and with the duration of functional recovery, but not with the extent of functional recovery itself. Such interhemispheric asymmetry was neither present in the intact monkeys, as expected, nor in F6 in all monkeys. In addition, the M1 lesion also impacted on the basal dendritic arborization of F3 layer V neurons. Neuronal density was clearly less affected by the M1 lesion in F3 layer III compared with layer V. We interpret the remote effect of M1 lesion onto the density of SMI-32-positive neurons and dendritic arborization in the SMAs bilaterally as the consequence of multiple factors, such as changes of connectivity, diaschisis and various mechanisms involved in cortical plasticity underlying the functional recovery from the M1 lesion.SIGNIFICANCE STATEMENT The motor system of macaque monkeys, in addition to be similarly organized as in humans, is a good candidate to study the impact of a focal lesion of the main contributor to voluntary movements, the primary motor cortex (M1), on non-primary motor cortical areas also involved in manual dexterity, both at behavioral and structural levels. Our results show that a unilateral permanent lesion of M1 hand area in nine monkeys affects the interhemispheric balance of the number of SMI-32-positive pyramidal neurons in the cortical layer V of the supplementary motor area, in a way strongly correlated to the lesion volume and duration of the incomplete functional recovery.

Ups and downs in catch-up saccades following single-pulse TMS-methodological considerations.

Transcranial magnetic stimulation (TMS) can interfere with smooth pursuit or with saccades initiated from a fixed position toward a fixed target, but little is known about the effect of TMS on catch-up saccade made to assist smooth pursuit. Here we explored the effect of TMS on catch-up saccades by means of a situation in which the moving target was driven by an external agent, or moved by the participants’ hand, a condition known to decrease the occurrence of catch-up saccade. Two sites of stimulation were tested, the vertex and M1 hand area. Compared to conditions with no TMS, we found a consistent modulation of saccadic activity after TMS such that it decreased at 40-100ms, strongly resumed at 100-160ms, and then decreased at 200-300ms. Despite this modulatory effect, the accuracy of catch-up saccade was maintained, and the mean saccadic activity over the 0-300ms period remained unchanged. Those findings are discussed in the context of studies showing that single-pulse TMS can induce widespread effects on neural oscillations as well as perturbations in the latency of saccades during reaction time protocols. At a more general level, despite challenges and interpretational limitations making uncertain the origin of this modulatory effect, our study provides direct evidence that TMS over presumably non-oculomotor regions interferes with the initiation of catch-up saccades, and thus offers methodological considerations for future studies that wish to investigate the underlying neural circuitry of catch-up saccades using TMS.