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Transcranial direct current stimulation (tDCS) is one of the non-invasive brain stimulation techniques that can improve motor functions. As bimanual motor actions require high motor cortical activations between hemispheres, applying bilateral anodal stimulation on left and right sides of primary motor cortex (M1) can improve for improvements in bimanual motor tasks. This study investigated which bilateral tDCS protocol effectively improves bimanual hand-grip force control capabilities in healthy young adults. We used three different bilateral tDCS protocols: (a) dual-anodal stimulation on the M1 of bilateral hemispheres (Bi-AA), (b) anodal–cathodal stimulation on the M1 of dominant and nondominant hemispheres (Bi-AC), and (c) sham stimulation (Sham). The results indicated that applying the Bi-AA significantly improved bilateral motor synergies estimated by uncontrolled manifold analysis relative to Sham. However, these differences were not observed in the comparison between Bi-AA and Bi-AC as well as between Bi-AC and Sham. These findings suggest that facilitating motor cortical activations between both hemispheres may be an additional option for advancing interlimb motor coordination patterns. [ABSTRACT FROM AUTHOR]

The corticospinal tract plays a major role in the control of voluntary limb movements, and its damage impedes voluntary limb control. We investigated the feasibility of closed-loop brain-controlled subdural spinal stimulation through a corticospinal interface for the modulation of wrist torque in the paralyzed forearm of monkeys with spinal cord injury at C4/C5. Subdural spinal stimulation of the preserved cervical enlargement activated multiple muscles on the paralyzed forearm and wrist torque in the range from flexion to ulnar-flexion. The magnitude of the evoked torque could be modulated by changing current intensity. We then employed the corticospinal interface designed to detect the firing rate of an arbitrarily selected "linked neuron" in the forearm territory of the primary motor cortex (M1) and convert it in real time to activity-contingent electrical stimulation of a spinal site caudal to the lesion. Linked neurons showed task-related activity that modulated the magnitude of the evoked torque and the activation of multiple muscles depending on the required torque. Unlinked neurons, which were independent of spinal stimulation and located in the vicinity of the linked neurons, exhibited task-related or -unrelated activity. Thus, monkeys were able to modulate the wrist torque of the paralyzed forearm by modulating the firing rate of M1 neurons including unlinked and linked neurons via the corticospinal interface. These results suggest that the corticospinal interface can replace the function of the corticospinal tract after spinal cord injury. [ABSTRACT FROM AUTHOR]

Introduction: How the human brain coordinates bimanual movements is not well-established. Methods: Here, we recorded neural signals from a paralyzed individual's left motor cortex during both unimanual and bimanual motor imagery tasks and quantified the representational interaction between arms by analyzing the tuning parameters of each neuron. Results: We found a similar proportion of neurons preferring each arm during unimanual movements, however, when switching to bimanual movements, the proportion of contralateral preference increased to 71.8%, indicating contralateral lateralization. We also observed a decorrelation process for each arm's representation across the unimanual and bimanual tasks. We further confined that these changes in bilateral relationships are mainly caused by the alteration of tuning parameters, such as the increased bilateral preferred direction (PD) shifts and the significant suppression in bilateral modulation depths (MDs), especially the ipsilateral side. Discussion: These results contribute to the knowledge of bimanual coordination and thus the design of cutting-edge bimanual brain-computer interfaces. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the changes in the functional connectivity of the cortical speech articulation network after anodal transcranial direct current stimulation (A-tDCS) over the left lip region of the primary motor cortex (M1) in subacute post-stroke patients with apraxia of speech (AoS), and the effect of A-tDCS on AoS. Methods: A total of 24 patients with post-stroke AoS were randomized into two groups and received A-tDCS over the left lip region of M1 (tDCS group)/sham tDCS (control group) as well as speech and language therapy two times per day for 5 days. Before and after the treatment, the AoS assessments and electroencephalogram (EEG) were evaluated. The cortical interconnections were measured using the EEG non-linear index of cross approximate entropy (C-ApEn). Results: The analysis of EEG showed that, after the treatment, the activated connectivity was all in the left hemisphere, and not only regions in the speech articulation network but also in the dorsal lateral prefrontal cortex (DLPFC) in the domain-general network were activated in the tDCS group. In contrast, the connectivity was confined to the right hemisphere and between bilateral DLPFC and bilateral inferior frontal gyrus (IFG) in the control group. In AoS assessments, the tDCS group improved significantly more than the control group in four of the five subtests. The results of multivariate linear regression analyses showed that only the group was significantly associated with the improvement of word repetition (P = 0.002). Conclusion: A-tDCS over the left lip region of M1 coupled with speech therapy could upregulate the connectivity of both speech-specific and domain-general networks in the left hemisphere. The improved articulation performance in patients with post-stroke AoSmight be related to the enhanced connectivity of networks in the left hemisphere induced by tDCS. [ABSTRACT FROM AUTHOR]

Background: Many studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief. Objective: This study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation. Methods: Using a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation. Results: Compared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS. Conclusions: The analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation.

Background: Since a stroke can impair bimanual activities, enhancing bimanual cooperation through motor skill learning may improve neurorehabilitation. Therefore, robotics and neuromodulation with transcranial direct current stimulation (tDCS) are promising approaches. To date, tDCS has failed to enhance bimanual motor control after stroke possibly because it was not integrating the hypothesis that the undamaged hemisphere becomes the major poststroke hub for bimanual control. Objective: We tested the following hypotheses: (I) In patients with chronic hemiparetic stroke training on a robotic device, anodal tDCS applied over the primary motor cortex of the undamaged hemisphere enhances bimanual motor skill learning compared to sham tDCS. (II) The severity of impairment correlates with the effect of tDCS on bimanual motor skill learning. (III) Bimanual motor skill learning is less efficient in patients than in healthy individuals (HI). Methods: A total of 17 patients with chronic hemiparetic stroke and 7 healthy individuals learned a complex bimanual cooperation skill on the REAplan® neurorehabilitation robot. The bimanual speed/accuracy trade-off (biSAT), bimanual coordination (biCo), and bimanual force (biFOP) scores were computed for each performance. In patients, real/sham tDCS was applied in a crossover, randomized, double-blind approach. Results: Compared to sham, real tDCS did not enhance bimanual motor skill learning, retention, or generalization in patients, and no correlation with impairment was noted. The healthy individuals performed better than patients on bimanualmotor skill learning, but generalization was similar in both groups. Conclusion: A short motor skill learning session with a robotic device resulted in the retention and generalization of a complex skill involving bimanual cooperation. The tDCS strategy that would best enhance bimanual motor skill learning after stroke remains unknown. [ABSTRACT FROM AUTHOR]

Understanding how and why MR signals and their associated relaxation rates vary with cortical depth could ultimately enable the noninvasive investigation of the laminar architecture of cerebral cortex in the living human brain. However, cortical gray matter is typically only a few millimeters thick, making it challenging to sample many cortical depths with the voxel sizes commonly used in MRI studies. Line-scan techniques provide a way to overcome this challenge and here we implemented a novel line-scan GESSE pulse sequence that allowed us to measure irreversible and reversible transverse relaxation rates—R 2 and R 2 ´, respectively—with extremely high resolution (250 μm) in the radial direction, perpendicular to the cortical surface. Eight healthy human subjects were scanned at 7 T using this sequence, with primary visual cortex (V1) targeted in three subjects and primary motor (M1) and somatosensory cortex (S1) targeted in the other five. In all three cortical areas, a peak in R 2 values near the central depths was seen consistently across subjects—an observation that has not been made before, to our knowledge. On the other hand, no consistent pattern was apparent for R 2 ´ values as a function of cortical depth. The intracortical R 2 peak reported here is unlikely to be explained by myelin content or by deoxyhemoglobin in the microvasculature; however, this peak is in accord with the laminar distribution of non-heme iron in these cortical areas, known from prior histology studies. Obtaining information about tissue microstructure via measurements of transverse relaxation (and other quantitative MR contrast mechanisms) at the extremely high radial resolutions achievable through the use of line-scan techniques could therefore bring us closer to being able to perform "in vivo histology" of the cerebral cortex. [ABSTRACT FROM AUTHOR]

The representation of muscles in the cortex can be mapped using navigated transcranial magnetic stimulation. The commonly employed measure to quantify the mapping are the center of gravity or the centroid of the region of excitability as well as its size. Determining these measures typically relies only on stimulation points that yield motorevoked potentials (MEPs); stimulations that do not elicit an MEP, i.e., non-MEP points, are ignored entirely. In this study, we show how incorporating non-MEP points may affect the estimates of the size and centroid of the excitable area in eight hand and forearm muscles after mono-phasic single-pulse TMS. We performed test-retest assessments in twenty participants and estimated the reliability of centroids and sizes of the corresponding areas using inter-class correlation coefficients. For most muscles, the reliability turned out good. As expected, removing the non-MEP points significantly decreased area sizes and area weights, suggesting that conventional approaches that do not account for non-MEP points are likely to overestimate the regions of excitability. [ABSTRACT FROM AUTHOR]

BackgroundSince a stroke can impair bimanual activities, enhancing bimanual cooperation through motor skill learning may improve neurorehabilitation. Therefore, robotics and neuromodulation with transcranial direct current stimulation (tDCS) are promising approaches. To date, tDCS has failed to enhance bimanual motor control after stroke possibly because it was not integrating the hypothesis that the undamaged hemisphere becomes the major poststroke hub for bimanual control.ObjectiveWe tested the following hypotheses: (I) In patients with chronic hemiparetic stroke training on a robotic device, anodal tDCS applied over the primary motor cortex of the undamaged hemisphere enhances bimanual motor skill learning compared to sham tDCS. (II) The severity of impairment correlates with the effect of tDCS on bimanual motor skill learning. (III) Bimanual motor skill learning is less efficient in patients than in healthy individuals (HI).MethodsA total of 17 patients with chronic hemiparetic stroke and 7 healthy individuals learned a complex bimanual cooperation skill on the REAplan® neurorehabilitation robot. The bimanual speed/accuracy trade-off (biSAT), bimanual coordination (biCo), and bimanual force (biFOP) scores were computed for each performance. In patients, real/sham tDCS was applied in a crossover, randomized, double-blind approach.ResultsCompared to sham, real tDCS did not enhance bimanual motor skill learning, retention, or generalization in patients, and no correlation with impairment was noted. The healthy individuals performed better than patients on bimanual motor skill learning, but generalization was similar in both groups.ConclusionA short motor skill learning session with a robotic device resulted in the retention and generalization of a complex skill involving bimanual cooperation. The tDCS strategy that would best enhance bimanual motor skill learning after stroke remains unknown.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT02308852, identifier: NCT02308852.

Some clinical studies have shown promising effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on pain relief. Nevertheless, a few studies reported no significant analgesic effects of tDCS, likely due to the complexity of clinical pain conditions. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds that are present in the clinical data. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) stimulation over M1 on sensitivity to experimental pain and assess whether these effects could be influenced by the pain-related cognitions and emotions. A randomized, double-blinded, crossover, and sham-controlled design was adopted. A total of 28 healthy participants received anodal, cathodal, or sham HD-tDCS over M1 (1 mA for 20 min) in different sessions, in which montage has the advantage of producing more focal stimulation. Using a cold pressor test, several indices reflecting the sensitivity to cold pain were measured immediately after HD-tDCS stimulation, such as cold pain threshold and tolerance and cold pain intensity and unpleasantness ratings. Results showed that only anodal HD-tDCS significantly increased cold pain threshold when compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain tolerance, pain intensity, and unpleasantness ratings. Correlation analysis revealed that individuals that a had lower level of attentional bias to negative information benefited more from attenuating pain intensity rating induced by anodal HD-tDCS. Therefore, single-session anodal HD-tDCS modulates the sensory-discriminative aspect of pain perception as indexed by the increased pain threshold. In addition, the modulating effects of HD-tDCS on attenuating pain intensity to suprathreshold pain could be influenced by the participant's negative attentional bias, which deserves to be taken into consideration in the clinical applications. [ABSTRACT FROM AUTHOR]

Some clinical studies have shown promising effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on pain relief. Nevertheless, a few studies reported no significant analgesic effects of tDCS, likely due to the complexity of clinical pain conditions. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds that are present in the clinical data. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) stimulation over M1 on sensitivity to experimental pain and assess whether these effects could be influenced by the pain-related cognitions and emotions. A randomized, double-blinded, crossover, and sham-controlled design was adopted. A total of 28 healthy participants received anodal, cathodal, or sham HD-tDCS over M1 (1 mA for 20 min) in different sessions, in which montage has the advantage of producing more focal stimulation. Using a cold pressor test, several indices reflecting the sensitivity to cold pain were measured immediately after HD-tDCS stimulation, such as cold pain threshold and tolerance and cold pain intensity and unpleasantness ratings. Results showed that only anodal HD-tDCS significantly increased cold pain threshold when compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain tolerance, pain intensity, and unpleasantness ratings. Correlation analysis revealed that individuals that a had lower level of attentional bias to negative information benefited more from attenuating pain intensity rating induced by anodal HD-tDCS. Therefore, single-session anodal HD-tDCS modulates the sensory-discriminative aspect of pain perception as indexed by the increased pain threshold. In addition, the modulating effects of HD-tDCS on attenuating pain intensity to suprathreshold pain could be influenced by the participant’s negative attentional bias, which deserves to be taken into consideration in the clinical applications.

Background: Upper-extremity hemiplegia after stroke remains a significant clinical problem. The supplementary motor area (SMA) is vital to the motor recovery outcomes of chronic stroke patients. Therefore, rebuilding the descending motor tract from the SMA to the paralyzed limb is a potential approach to restoring arm motor function after stroke. Paired associative stimulation (PAS), which is based on Hebbian theory, is a potential method for reconstructing the connections in the impaired motor neural circuits. The study described in this protocol aims to assess the effects of cortico–peripheral Hebbian-type stimulation (HTS), involving PAS, for neural circuit reconstruction to rescue the paralyzed arm after stroke. Methods: The study is a 4-month double-blind randomized sham-controlled clinical trial. We will recruit 90 post-stroke individuals with mild to moderate upper limb paralysis. Based on a 1:1 ratio, the participants will be randomly assigned to the HTS and sham groups. Each participant will undergo 5-week HTS or sham stimulation. Assessments will be conducted at baseline, immediately after the 5-week treatment, and at a 3-month follow-up. The primary outcome will be the Wolf Motor Function Test (WMFT). The secondary outcomes will be Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Functional Independence Measure (FIM), and functional near-infrared spectroscopy (fNIRS) parameters. The adverse events will be recorded throughout the study. Discussion: Upper-limb paralysis in stroke patients is due to neural circuit disruption, so the reconstruction of effective motor circuits is a promising treatment approach. Based on its anatomical structure and function, the SMA is thought to compensate for motor dysfunction after focal brain injury at the cortical level. Our well-designed randomized controlled trial will allow us to analyze the clinical efficacy of this novel Hebbian theory-based neuromodulation strategy regarding promoting the connection between the cortex and peripheral limb. The results may have significance for the development and implementation of effective neurorehabilitation treatments. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2000039949]. [ABSTRACT FROM AUTHOR]

Deciding between different voluntary movements implies a continuous control of the competition between potential actions. Many theories postulate a leading role of prefrontal cortices in this executive function, but strong evidence exists that a motor region like the primary motor cortex (M1) is also involved, possibly via inhibitory mechanisms. This was already shown during the pre-movement decision period, but not after movement onset. For this pilot experiment we designed a new task compatible with the dynamics of post-onset control to study the silent period (SP) duration, a pause in electromyographic activity after single-pulse transcranial magnetic stimulation that reflects inhibitory mechanisms. A careful analysis of the SP during the ongoing movement indicates a gradual increase in inhibitory mechanisms with the level of competition, consistent with an increase in mutual inhibition between alternative movement options. However, we also observed a decreased SP duration for high-competition trials associated with change-of-mind inflections in their trajectories. Our results suggest a new post-onset adaptive process that consists in a transient reduction of GABAergic inhibition within M1 for highly conflicting situations. We propose that this reduced inhibition softens the competition between concurrent motor options, thereby favoring response vacillation, an adaptive strategy that proved successful at improving behavioral performance. [ABSTRACT FROM AUTHOR]

Abstract Background Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has the potential to induce motor cortical plasticity in humans. It is well known that motor cortical plasticity plays an essential role in motor learning and recovery in patients with stroke and neurodegenerative disorders. However, it remains unclear how cognitive function influences motor cortical plasticity induced by tDCS. The present study aimed to investigate whether anodal tDCS combined with attention to a target muscle could enhance motor cortical plasticity and improve motor learning in healthy individuals. Methods Thirty-three healthy volunteers were assigned to two experiments. In experiment 1, there were three interventional conditions: 1) anodal tDCS was applied while participants paid attention to the first dorsal interosseous (FDI) muscle, 2) anodal tDCS was applied while participants paid attention to the sound, and 3) anodal tDCS was applied without the participants paying attention to the FDI muscle or the sound. Anodal tDCS (2 mA, 10 min) was applied over the primary motor cortex (M1). Changes in motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were assessed before and immediately after (0 min), and then 10 min, 30 min, and 60 min after each intervention. In experiment 2, we investigated whether the combination of anodal tDCS and attention to the abductor pollicis brevis (APB) muscle could facilitate the learning of a ballistic thumb movement. Results Anodal tDCS increased cortical excitability in all conditions immediately after the stimulation. Significant increases in MEPs and significant decreases in SICI were observed for at least 60 min after anodal tDCS, but only when participants paid attention to the FDI muscle. In contrast, no significant changes in ICF were observed in any condition. In experiment 2, the combination of tDCS and attention to the APB muscle significantly enhanced the acquisition of a ballistic thumb movement. The higher performance was still observed 7 days after the stimulation. Conclusions This study shows that anodal tDCS over M1 in conjunction with attention to the target muscle enhances motor cortex plasticity and improves motor learning in healthy adults. These findings suggest that a combination of attention and tDCS may be an effective strategy to promote rehabilitation training in patients with stroke and neurodegenerative disorders. Trial registration Retrospectively registered ( UMIN000036848 ).

BackgroundUpper-extremity hemiplegia after stroke remains a significant clinical problem. The supplementary motor area (SMA) is vital to the motor recovery outcomes of chronic stroke patients. Therefore, rebuilding the descending motor tract from the SMA to the paralyzed limb is a potential approach to restoring arm motor function after stroke. Paired associative stimulation (PAS), which is based on Hebbian theory, is a potential method for reconstructing the connections in the impaired motor neural circuits. The study described in this protocol aims to assess the effects of cortico–peripheral Hebbian-type stimulation (HTS), involving PAS, for neural circuit reconstruction to rescue the paralyzed arm after stroke.MethodsThe study is a 4-month double-blind randomized sham-controlled clinical trial. We will recruit 90 post-stroke individuals with mild to moderate upper limb paralysis. Based on a 1:1 ratio, the participants will be randomly assigned to the HTS and sham groups. Each participant will undergo 5-week HTS or sham stimulation. Assessments will be conducted at baseline, immediately after the 5-week treatment, and at a 3-month follow-up. The primary outcome will be the Wolf Motor Function Test (WMFT). The secondary outcomes will be Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Functional Independence Measure (FIM), and functional near-infrared spectroscopy (fNIRS) parameters. The adverse events will be recorded throughout the study.DiscussionUpper-limb paralysis in stroke patients is due to neural circuit disruption, so the reconstruction of effective motor circuits is a promising treatment approach. Based on its anatomical structure and function, the SMA is thought to compensate for motor dysfunction after focal brain injury at the cortical level. Our well-designed randomized controlled trial will allow us to analyze the clinical efficacy of this novel Hebbian theory-based neuromodulation strategy regarding promoting the connection between the cortex and peripheral limb. The results may have significance for the development and implementation of effective neurorehabilitation treatments.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2000039949].

Many studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief. This study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation. Using a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation. Compared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS. The analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation. • Effects of a-tDCS and high-frequency tRNS + DC-offset on pain were assessed. • A single-session a-tDCS induced immediate analgesic effects. • A single-session tRNS induced both immediate and sustained analgesic effects. • Analgesic effects of a-tDCS were greater when pain was expected with uncertainty. • Analgesic effects of tRNS were mediated by decreasing pain expectation. [ABSTRACT FROM AUTHOR]

Age-related changes in cortico-cortical connectivity in the human motor network in older adults are associated with declines in hand dexterity. Posterior parietal cortex (PPC) is strongly interconnected with motor areas and plays a critical role in many aspects of motor planning. Functional connectivity measures derived from dual-site transcranial magnetic stimulation (dsTMS) studies have found facilitatory inputs from PPC to ipsilateral primary motor cortex (M1) in younger adults. In this study, we investigated whether facilitatory inputs from PPC to M1 are altered by age. We used dsTMS in a conditioning-test paradigm to characterize patterns of functional connectivity between the left PPC and ipsilateral M1 and a standard pegboard test to assess skilled hand motor function in 13 young and 13 older adults. We found a PPC-M1 facilitation in young adults but not older adults. Older adults also showed a decline in motor performance compared to young adults. We conclude that the reduced PPC-M1 facilitation in older adults may be an early marker of age-related decline in the neural control of movement.

BackgroundTranscranial direct current stimulation (TDCS) targeting the primary motor hand area (M1-HAND) may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging (fMRI) can probe after-effects of TDCS on regional neural activity on a whole-brain level.ObjectiveUsing a double-blinded cross-over design, we investigated whether the individual change in corticospinal excitability after TDCS of M1-HAND is associated with changes in task-related regional activity in cortical motor areas.MethodsSeventeen healthy volunteers (10 women) received 20 min of real (0.75 mA) or sham TDCS on separate days in randomized order. Real and sham TDCS used the classic bipolar set-up with the anode placed over right M1-HAND. Before and after each TDCS session, we recorded motor evoked potentials (MEP) from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation(TMS) of left M1-HAND and performed whole-brain fMRI at 3 Tesla while participants completed a visuomotor tracking task with their left hand. We also assessed the difference in MEP latency when applying anterior-posterior and latero-medial TMS pulses to the precentral hand knob (AP-LM MEP latency).ResultsReal TDCS had no consistent aftereffects on mean MEP amplitude, task-related activity or motor performance. Individual changes in MEP amplitude, measured directly after real TDCS showed a positive linear relationship with individual changes in task-related activity in the supplementary motor area and AP-LM MEP latency.ConclusionFunctional aftereffects of classical bipolar anodal TDCS of M1-HAND on the motor system vary substantially across individuals. Physiological features upstream from the primary motor cortex may determine how anodal TDCS changes corticospinal excitability.

Background: The effects of transcranial direct current stimulation (tDCS) on specific sports skills have received extensive attention, however, it is difficult to accurately determine its effect on physical performance due to the complexity of the tasks. The objective of this study was to investigate the effects of uni-hemispheric anodal tDCS of the motor cortex (M1) on the indirect measurement of physical ability in healthy men. Methods: Thirteen healthy, right-leg-dominant men aged between 21 and 32 years (26.53 ± 2.73 years) participated in two different experimental conditions in a randomized, single-blinded crossover design: anodal stimulation (a-tDCS) and sham-tDCS (2 mA for 20 minutes targeting the left M1 contralateral to dominant leg). Before and immediately after the tDCS stimulation, participants completed the standing long jump (SLJ) and sidestep test (SST), and their blood pressure and heart rate were checked for the safety of tDCS application. Results: No significant difference was observed between a-tDCS and sham-tDCS (F(1,24) = 0.02, p = 0.86, ηp2 = 0.001) on SLJ. Also, no significant changes in SLJ were observed between pre- and post-stimulation sessions for both conditions (F(1,24) = 1.18, p = 0.28, ηp2 = 0.047). Similarly, SST scores were not significantly different from a-tDCS and sham-tDCS condition (F(1,24) = 0.57, p = 0.45, ηp2 = 0.024). Significant changes in SST were not observed throughout the experiment sessions for both stimulation conditions (F(1,24) = 0.12, p = 0.73, ηp2 = 0.005). Conclusions: The uni-hemispheric a-tDCS applied over the M1 for 20 minutes may not be a valuable tool to obtain the physical performance benefits from the tasks that require bilateral lower limb power output, such as SLJ and SST.

Background: Transcranial direct current stimulation (TDCS) targeting the primary motor hand area (M1-HAND) may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging (fMRI) can probe after-effects of TDCS on regional neural activity on a whole-brain level. Objective: Using a double-blinded cross-over design, we investigated whether the individual change in corticospinal excitability after TDCS of M1-HAND is associated with changes in task-related regional activity in cortical motor areas. Methods: Seventeen healthy volunteers (10 women) received 20 min of real (0.75 mA) or sham TDCS on separate days in randomized order. Real and sham TDCS used the classic bipolar set-up with the anode placed over right M1-HAND. Before and after each TDCS session, we recorded motor evoked potentials (MEP) from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation(TMS) of left M1-HAND and performed whole-brain fMRI at 3 Tesla while participants completed a visuomotor tracking task with their left hand. We also assessed the difference in MEP latency when applying anterior-posterior and latero-medial TMS pulses to the precentral hand knob (AP-LM MEP latency). Results: Real TDCS had no consistent aftereffects on mean MEP amplitude, task-related activity or motor performance. Individual changes in MEP amplitude, measured directly after real TDCS showed a positive linear relationship with individual changes in task-related activity in the supplementary motor area and AP-LM MEP latency. Conclusion: Functional aftereffects of classical bipolar anodal TDCS of M1-HAND on the motor system vary substantially across individuals. Physiological features upstream from the primary motor cortex may determine how anodal TDCS changes corticospinal excitability. [ABSTRACT FROM AUTHOR]

Age-related changes in cortico-cortical connectivity in the human motor network in older adults are associated with declines in hand dexterity. Posterior parietal cortex (PPC) is strongly interconnected with motor areas and plays a critical role in many aspects of motor planning. Functional connectivity measures derived from dual-site transcranial magnetic stimulation (dsTMS) studies have found facilitatory inputs from PPC to ipsilateral primary motor cortex (M1) in younger adults. In this study, we investigated whether facilitatory inputs from PPC to M1 are altered by age. We used dsTMS in a conditioning-test paradigm to characterize patterns of functional connectivity between the left PPC and ipsilateral M1 and a standard pegboard test to assess skilled hand motor function in 13 young and 13 older adults. We found a PPC-M1 facilitation in young adults but not older adults. Older adults also showed a decline in motor performance compared to young adults. We conclude that the reduced PPC-M1 facilitation in older adults may be an early marker of age-related decline in the neural control of movement. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to measure diffusion signals within the cerebral cortex using the line‐scan technique to achieve extremely high resolution in the radial direction (ie, perpendicular to the cortical surface) and to demonstrate the utility of these measurements for investigating laminar architecture in the living human brain. Methods: Line‐scan diffusion data with 250‐500 micron radial resolution were acquired at 7 T on 8 healthy volunteers, with each line prescribed perpendicularly to primary somatosensory cortex (S1) and primary motor cortex (M1). Apparent diffusion coefficients, fractional anisotropy values, and radiality indices were measured as a function of cortical depth. Results: In the deep layers of S1, we found evidence for high anisotropy and predominantly tangential diffusion, with low anisotropy observed in superficial S1. In M1, moderate anisotropy and predominantly radial diffusion was seen at almost all cortical depths. These patterns were consistent across subjects and were conspicuous without averaging data across different locations on the cortical sheet. Conclusion: Our results are in accord with the myeloarchitecture of S1 and M1, known from prior histology studies: in S1, dense bands of tangential myelinated fibers run through the deep layers but not the superficial ones, and in M1, radial myelinated fibers are prominent at most cortical depths. This work therefore provides support for the idea that high‐resolution diffusion signals, measured with the line‐scan technique and receiving a boost in SNR at 7 T, may serve as a sensitive probe of in vivo laminar architecture. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD., Competing Interests: Conflict of Interest The authors declare no competing interests.

The control of arm movements through intracortical brain–machine interfaces (BMIs) mainly relies on the activities of the primary motor cortex (M1) neurons and mathematical models that decode their activities. Recent research on decoding process attempts to not only improve the performance but also simultaneously understand neural and behavioral relationships. In this study, we propose an efficient decoding algorithm using a deep canonical correlation analysis (DCCA), which maximizes correlations between canonical variables with the non-linear approximation of mappings from neuronal to canonical variables via deep learning. We investigate the effectiveness of using DCCA for finding a relationship between M1 activities and kinematic information when non-human primates performed a reaching task with one arm. Then, we examine whether using neural activity representations from DCCA improves the decoding performance through linear and non-linear decoders: a linear Kalman filter (LKF) and a long short-term memory in recurrent neural networks (LSTM-RNN). We found that neural representations of M1 activities estimated by DCCA resulted in more accurate decoding of velocity than those estimated by linear canonical correlation analysis, principal component analysis, factor analysis, and linear dynamical system. Decoding with DCCA yielded better performance than decoding the original FRs using LSTM-RNN (6.6 and 16.0% improvement on average for each velocity and position, respectively; Wilcoxon rank sum test, p < 0.05). Thus, DCCA can identify the kinematics-related canonical variables of M1 activities, thus improving the decoding performance. Our results may help advance the design of decoding models for intracortical BMIs.

Objective: Associative motor cortical plasticity can be non-invasively induced by paired median nerve electric stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). This study investigates whether a simultaneous motor reaction of the other hand advances the associative plasticity in M1.Methods: Twenty-four right-handed subjects received conventional paired associative stimulation (PAS) and PAS with simultaneous motor reaction (PASmr) with at least a 1-week interval. The PASmr protocol additionally included left abductor pollicis brevis muscle movement responding to a digital sound. The motor reaction time was individually measured. The M1 excitability was examined by the motor evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) before and after the PAS protocols.Results: The conventional PAS protocol significantly facilitated MEP and suppressed SICI. A negative correlation between the reaction time and the MEP change, and a positive correlation between the reaction time and the ICF change were found in the PASmr protocol. By subgrouping analysis, we further found significant facilitation of MEP and a reduction of ICF in the subjects with fast reaction times but not in those with slow reaction times.Conclusion: Synchronized motor reaction ipsilateral to the stimulated M1 induces associative M1 motor plasticity through the spike-timing dependent principle. MEP and ICF change could represent this kind of plasticity. The current findings provide a novel insight into designing rehabilitation programs concerning motor function.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can facilitate motor learning, but it has not been established how stimulation to other brain regions impacts online and offline motor sequence learning, as well as long-term retention. Here, we completed three experiments comparing the effects of tDCS and sham stimulation to the prefrontal cortex (PFC), M1, and the supplementary motor area complex to understand the contributions of these brain regions to motor sequence learning. In Experiment 1, we found that both left and right PFC tDCS groups displayed a slowing in learning in both reaction time and number of chunks, whereas stimulation over M1 improved both metrics over the course of three sessions. To better understand the sequence learning impairment of left PFC anodal stimulation, we tested a left PFC cathodal tDCS group in Experiment 2. The cathodal group demonstrated learning impairments similar to the left PFC anodal stimulation group. In Experiment 3, a subset of participants from the left PFC, M1, and sham tDCS groups of Experiment 1 returned to complete a single session without tDCS on the same sequences assigned to them 1 year previously. We found that the M1 tDCS group reduced reaction time at a faster rate relative to the sham and left PFC groups, demonstrating faster relearning after a one-year delay. Thus, our findings suggest that, regardless of the polarity of stimulation, tDCS to PFC impairs sequence learning, whereas stimulation to M1 facilitates learning and relearning, especially in terms of chunk formation.

The application of repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) could influence the intrinsic brain activity in the sensorimotor network (SMN). However, how rTMS modulates the topological organization of the SMN remains unclear. In this study, we employed resting-state fMRI to investigate the topological alterations in the functional SMN after application of different frequency rTMS over the left M1. To accomplish this, we collected MRI data from 45 healthy participants who were randomly divided into three groups based on rTMS frequency (HF, high-frequency 3 Hz; LF, low-frequency 1 Hz; and SHAM). Individual large-scale functional SMN was constructed by correlating the mean time series among 29 regions of interest (ROI) in the SMN and was fed into graph-based network analyses at multiple levels of global organization and nodal centrality. Our results showed that compared with the network metrics before rTMS stimulation, the left paracentral lobule (PCL) exhibited reduced nodal degree and betweenness centrality in the LF group after rTMS, while the right supplementary motor area (SMA) exhibited reduced nodal betweenness centrality in the HF group after rTMS. Moreover, rTMS-related alterations in nodal metrics might have been attributable to the changes in connectivity patterns and local activity of the affected nodes. These findings reflected the potential of using rTMS over M1 as an effective intervention to promote motor function rehabilitation.

Experiments on 23 white male rats (250 g) analyzed the spike activity of individual neurons in the substantia nigra pars compacta (SNc, 242 neurons, n = 11) and substantia nigra pars reticulata (SNr, 289 neurons, n = 12) during high-frequency stimulation of the primary motor cortex (M1)in normal animals and in animals with a rotenone model of Parkinson's disease (BP). SNc neurons in the model of PD showed a complete absence of depressor effects induced by stimulation, though tetanic potentiation was accompanied by posttetanic potentiation and depression at levels 1.65 and 2.02 times greater than in normal animals. In SNr neurons in normal animals, tetanic potentiation, accompanied by post-tetanic potentiation and depression, was 2.37 times greater than tetanic depression, while in the model of PD the levels of both depressor and excitatory activity induced by stimulation were below normal. Spike activity frequency in SNc and SNr neurons preceding and accompanying stimulation was significantly greater than normal in the model of PD. This is evidence for excitotoxicity accompanying neurodegenerative damage, which is completed by neuron apoptosis and death. In SNr neurons, both depressor and excitatory reactions accompanying stimulation were markedly dominant over those in SNc neurons, which is evidence for more extensive cortical projections to the SNr. Furthermore, SNc neurons demonstrated greater susceptibility to pathological changes due to poststimulus depressor effects than SNr neurons, with formation of more marked excitatory effects, which is evidence of a greater involvement of the SNc in PD. In the model of PD, lacking stimulation-induced depressor effects and more marked excitatory effects in SNc neurons, SNr neurons retained their depressor reactions and relatively decreased excitatory reactions, which is evidence of a lower level of susceptibility of SNr neurons to excitotoxicity, extreme increases in the excitability of surviving neurons compensating for the lack of excitation of dead cells. [ABSTRACT FROM AUTHOR]

Objective : Associative motor cortical plasticity can be non-invasively induced by paired median nerve electric stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). This study investigates whether a simultaneous motor reaction of the other hand advances the associative plasticity in M1. Methods : Twenty-four right-handed subjects received conventional paired associative stimulation (PAS) and PAS with simultaneous motor reaction (PASmr) with at least a 1-week interval. The PASmr protocol additionally included left abductor pollicis brevis muscle movement responding to a digital sound. The motor reaction time was individually measured. The M1 excitability was examined by the motor evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) before and after the PAS protocols. Results : The conventional PAS protocol significantly facilitated MEP and suppressed SICI. A negative correlation between the reaction time and the MEP change, and a positive correlation between the reaction time and the ICF change were found in the PASmr protocol. By subgrouping analysis, we further found significant facilitation of MEP and a reduction of ICF in the subjects with fast reaction times but not in those with slow reaction times. Conclusion : Synchronized motor reaction ipsilateral to the stimulated M1 induces associative M1 motor plasticity through the spike-timing dependent principle. MEP and ICF change could represent this kind of plasticity. The current findings provide a novel insight into designing rehabilitation programs concerning motor function. [ABSTRACT FROM AUTHOR]

The control of arm movements through intracortical brain–machine interfaces (BMIs) mainly relies on the activities of the primary motor cortex (M1) neurons and mathematical models that decode their activities. Recent research on decoding process attempts to not only improve the performance but also simultaneously understand neural and behavioral relationships. In this study, we propose an efficient decoding algorithm using a deep canonical correlation analysis (DCCA), which maximizes correlations between canonical variables with the non-linear approximation of mappings from neuronal to canonical variables via deep learning. We investigate the effectiveness of using DCCA for finding a relationship between M1 activities and kinematic information when non-human primates performed a reaching task with one arm. Then, we examine whether using neural activity representations from DCCA improves the decoding performance through linear and non-linear decoders: a linear Kalman filter (LKF) and a long short-term memory in recurrent neural networks (LSTM-RNN). We found that neural representations of M1 activities estimated by DCCA resulted in more accurate decoding of velocity than those estimated by linear canonical correlation analysis, principal component analysis, factor analysis, and linear dynamical system. Decoding with DCCA yielded better performance than decoding the original FRs using LSTM-RNN (6.6 and 16.0% improvement on average for each velocity and position, respectively; Wilcoxon rank sum test, p < 0.05). Thus, DCCA can identify the kinematics-related canonical variables of M1 activities, thus improving the decoding performance. Our results may help advance the design of decoding models for intracortical BMIs. [ABSTRACT FROM AUTHOR]

Single-pulse transcranial magnetic stimulation (spTMS) studies report that movement observation facilitates corticospinal excitability in primary motor cortex (M1) in a muscle-specific manner. However, motor evoked potentials (MEPs) elicited by spTMS are known to reflect the summation of several descending volleys in corticospinal neurons which are evoked via mono- and polysynaptic inputs (so-called indirect waves or I-waves). It is unclear which of these components contribute to the muscle-specific modulation of M1 during action observation. The interactions between different I-waves are reflected in the facilitatory peaks elicited with a short-intracortical facilitation (SICF) protocol when two pulses are sent to M1 at precise intervals (i.e., 1.3, 2.5 or 4.1 ms). Here, we explored the modulation of early and late SICF peaks during action observation by measuring highly specific MEP amplitude changes measured in two muscles (index, FDI and little finger, ADM) while participants observed two different actions (precision and whole-hand grip). Our results demonstrate that both early (1.3 ms) and late (2.5 and 4.1 ms) SICF peaks are modulated in the context of movement observation. However, only the second peak (ISI 2.5 ms) was significantly associated with the muscle-specific modulation of corticospinal excitability as measured with spTMS. This late SICF peak is believed to reflect the activity cortico-cortical pathways involved in the facilitation of muscle-specific representations in M1. Thus, our findings suggest that movement observation leads to widespread activation of different neural circuits within M1, including those mediating cortico-cortical communication. [ABSTRACT FROM AUTHOR]

• LFPs were recorded in the M1 and the SMA of parkinsonian primates. • Machine learnings were used to discriminate healthy, parkinsonian, and on-medication parkinsonian states. • Parameters discriminating these states were different depending on cortical areas. • This study contributes to understanding parkinsonism and to develop on-demand therapies. The present study compares the cortical local field potentials (LFPs) in the primary motor cortex (M1) and the supplementary motor area (SMA) of non-human primates rendered Parkinsonian with administration of dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The dynamic of the LFPs was investigated under several mathematical frameworks and machine learning was used to discriminate the recordings based on these features between healthy, parkinsonian with off-medication and parkinsonian with on-medication states. The importance of each feature in the discrimination process was further investigated. The dynamic of the LFPs in M1 and SMA was affected regarding its variability (time domain analysis), oscillatory activities (frequency domain analysis) and complex patterns (non-linear domain analysis). Machine learning algorithms achieved accuracy near 0.90 for comparisons between conditions. The TreeBagger algorithm provided best accuracy. The relative importance of these features differed with the cortical location, condition and treatment. Overall, the most important features included beta oscillation, fractal dimension, gamma oscillation, entropy and asymmetry of amplitude fluctuation. The importance of features in discriminating between normal and pathological states, and on- or off-medication states depends on the pair-comparison and it is region-specific. These findings are discussed regarding the refinement of current models for movement disorders and the development of on-demand therapies. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can facilitate motor learning, but it has not been established how stimulation to other brain regions impacts online and offline motor sequence learning, as well as long-term retention. Here, we completed three experiments comparing the effects of tDCS and sham stimulation to the prefrontal cortex (PFC), M1, and the supplementary motor area complex to understand the contributions of these brain regions to motor sequence learning. In Experiment 1, we found that both left and right PFC tDCS groups displayed a slowing in learning in both reaction time and number of chunks, whereas stimulation over M1 improved both metrics over the course of three sessions. To better understand the sequence learning impairment of left PFC anodal stimulation, we tested a left PFC cathodal tDCS group in Experiment 2. The cathodal group demonstrated learning impairments similar to the left PFC anodal stimulation group. In Experiment 3, a subset of participants from the left PFC, M1, and sham tDCS groups of Experiment 1 returned to complete a single session without tDCS on the same sequences assigned to them 1 year previously. We found that the M1 tDCS group reduced reaction time at a faster rate relative to the sham and left PFC groups, demonstrating faster relearning after a one-year delay. Thus, our findings suggest that, regardless of the polarity of stimulation, tDCS to PFC impairs sequence learning, whereas stimulation to M1 facilitates learning and relearning, especially in terms of chunk formation. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has the potential to induce motor cortical plasticity in humans. It is well known that motor cortical plasticity plays an essential role in motor learning and recovery in patients with stroke and neurodegenerative disorders. However, it remains unclear how cognitive function influences motor cortical plasticity induced by tDCS. The present study aimed to investigate whether anodal tDCS combined with attention to a target muscle could enhance motor cortical plasticity and improve motor learning in healthy individuals.Methods: Thirty-three healthy volunteers were assigned to two experiments. In experiment 1, there were three interventional conditions: 1) anodal tDCS was applied while participants paid attention to the first dorsal interosseous (FDI) muscle, 2) anodal tDCS was applied while participants paid attention to the sound, and 3) anodal tDCS was applied without the participants paying attention to the FDI muscle or the sound. Anodal tDCS (2 mA, 10 min) was applied over the primary motor cortex (M1). Changes in motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were assessed before and immediately after (0 min), and then 10 min, 30 min, and 60 min after each intervention. In experiment 2, we investigated whether the combination of anodal tDCS and attention to the abductor pollicis brevis (APB) muscle could facilitate the learning of a ballistic thumb movement.Results: Anodal tDCS increased cortical excitability in all conditions immediately after the stimulation. Significant increases in MEPs and significant decreases in SICI were observed for at least 60 min after anodal tDCS, but only when participants paid attention to the FDI muscle. In contrast, no significant changes in ICF were observed in any condition. In experiment 2, the combination of tDCS and attention to the APB muscle significantly enhanced the acquisition of a ballistic thumb movement. The higher performance was still observed 7 days after the stimulation.Conclusions: This study shows that anodal tDCS over M1 in conjunction with attention to the target muscle enhances motor cortex plasticity and improves motor learning in healthy adults. These findings suggest that a combination of attention and tDCS may be an effective strategy to promote rehabilitation training in patients with stroke and neurodegenerative disorders.Trial Registration: Retrospectively registered (UMIN000036848). [ABSTRACT FROM AUTHOR]

The dynamical systems view of movement generation in motor cortical areas has emerged as an effective way to explain the firing properties of populations of neurons recorded from these regions. Recently, many studies have focused on finding low-dimensional representations of these dynamical systems during voluntary reaching and grasping behaviors carried out by the forelimbs. One such model, the Poisson linear-dynamical-system (PLDS) model, has been shown to extract dynamics which can be used to decode reaching kinematics. However, few have investigated these dynamics, especially in non-human primates, during behaviors such as locomotion, which may involve motor cortex to a lesser degree. Here, we focused on unconstrained quadrupedal locomotion, and investigated whether unsupervised latent state-space models can extract low-dimensional dynamics while preserving information about hind-limb kinematics. Spiking activity from the leg area of primary motor cortex of rhesus macaques was recorded simultaneously with hind-limb joint positions during ambulation across a corridor, ladder, and on a treadmill at various speeds. We found that PLDS models can extract stereotyped low-dimensional neural trajectories from these neurons phase-locked to the gait cycle, and that distinct trajectories emerge depending on the speed and class of behavior. Additionally, it was possible to decode both the hind-limb kinematics and the gait phase from these inferred trajectories just as well or better than from the full neural population (18-80 neurons) with only 12 dimensions. Our results demonstrate that kinematics and gait phase during various locomotion tasks are well represented in low-dimensional latent dynamics inferred from motor cortex population activity.

Motor imagery refers to the phenomenon of imagining performing an action without action execution. Motor imagery and motor execution are assumed to share a similar underlying neural system that involves primary motor cortex (M1). Previous studies have focused on motor imagery of manual actions, but articulatory motor imagery has not been investigated. In this study, transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) from the articulatory muscles [orbicularis oris (OO)] as well as from hand muscles [first dorsal interosseous (FDI)]. Twenty participants were asked to execute or imagine performing a simple squeezing task involving a pair of tweezers, which was comparable across both effectors. MEPs were elicited at six time points (50, 150, 250, 350, 450, 550 ms post-stimulus) to track the time course of M1 involvement in both lip and hand tasks. The results showed increased MEP amplitudes for action execution compared to rest for both effectors at time points 350, 450 and 550 ms, but we found no evidence of increased cortical activation for motor imagery. The results indicate that motor imagery does not involve M1 for simple tasks for manual or articulatory muscles. The results have implications for models of mental imagery of simple articulatory gestures, in that no evidence is found for somatotopic activation of lip muscles in sub-phonemic contexts during motor imagery of such tasks, suggesting that motor simulation of relatively simple actions does not involve M1.

The dynamical systems view of movement generation in motor cortical areas has emerged as an effective way to explain the firing properties of populations of neurons recorded from these regions. Recently, many studies have focused on finding low-dimensional representations of these dynamical systems during voluntary reaching and grasping behaviors carried out by the forelimbs. One such model, the Poisson linear-dynamical-system (PLDS) model, has been shown to extract dynamics which can be used to decode reaching kinematics. However, few have investigated these dynamics, especially in non-human primates, during behaviors such as locomotion, which may involve motor cortex to a lesser degree. Here, we focused on unconstrained quadrupedal locomotion, and investigated whether unsupervised latent state-space models can extract low-dimensional dynamics while preserving information about hind-limb kinematics. Spiking activity from the leg area of primary motor cortex of rhesus macaques was recorded simultaneously with hind-limb joint positions during ambulation across a corridor, ladder, and on a treadmill at various speeds. We found that PLDS models can extract stereotyped low-dimensional neural trajectories from these neurons phase-locked to the gait cycle, and that distinct trajectories emerge depending on the speed and class of behavior. Additionally, it was possible to decode both the hind-limb kinematics and the gait phase from these inferred trajectories just as well or better than from the full neural population (18-80 neurons) with only 12 dimensions. Our results demonstrate that kinematics and gait phase during various locomotion tasks are well represented in low-dimensional latent dynamics inferred from motor cortex population activity. [ABSTRACT FROM AUTHOR]

Motor imagery refers to the phenomenon of imagining performing an action without action execution. Motor imagery and motor execution are assumed to share a similar underlying neural system that involves primary motor cortex (M1). Previous studies have focused on motor imagery of manual actions, but articulatory motor imagery has not been investigated. In this study, transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) from the articulatory muscles [ orbicularis oris (OO)] as well as from hand muscles [ first dorsal interosseous (FDI)]. Twenty participants were asked to execute or imagine performing a simple squeezing task involving a pair of tweezers, which was comparable across both effectors. MEPs were elicited at six time points (50, 150, 250, 350, 450, 550 ms post-stimulus) to track the time course of M1 involvement in both lip and hand tasks. The results showed increased MEP amplitudes for action execution compared to rest for both effectors at time points 350, 450 and 550 ms, but we found no evidence of increased cortical activation for motor imagery. The results indicate that motor imagery does not involve M1 for simple tasks for manual or articulatory muscles. The results have implications for models of mental imagery of simple articulatory gestures, in that no evidence is found for somatotopic activation of lip muscles in sub-phonemic contexts during motor imagery of such tasks, suggesting that motor simulation of relatively simple actions does not involve M1. [ABSTRACT FROM AUTHOR]

One of the critical factors that guide choice behavior is the prior bias of the decision-maker with respect to different options, namely, the relative readiness by which the decision-maker opts for a specific choice. Although previous neuroimaging work has shown decision bias related activity in the orbitofrontal cortex, intraparietal sulcus (IPS) and dorsolateral prefrontal cortex, in a recent work by Javadi et al. (2015), primary motor cortex was also implicated. By applying transcranial direct current stimulation (tDCS), they have revealed a causal role of the primary motor cortex excitability in the induction of response time (RT) differences and decision bias in the form of choice probability. The current study aimed to replicate these recent findings with an experimental design that contained a sham group to increase experimental control and an additional testing phase to investigate the possible after-effects of tDCS. The conventional decision outputs such as choice proportion and RT were analyzed along with the theory-driven estimates of choice bias and non-decision related components of RTs (e.g., motor implementation speed of choices made). None of the statistical comparisons favored the alternative hypotheses over the null hypotheses. Consequently, previous findings regarding the effect of primary motor cortex excitability on choice bias and response times could not be replicated with a more controlled experimental design that is recommended for tDCS studies (Horvath et al., 2015). This empirical discrepancy between the two studies adds to the evidence demonstrating inconsistent effects of tDCS in establishing causal relationships between cortical excitability and motor behavior.

One of the critical factors that guide choice behavior is the prior bias of the decision-maker with respect to different options, namely, the relative readiness by which the decision-maker opts for a specific choice. Although previous neuroimaging work has shown decision bias related activity in the orbitofrontal cortex, intraparietal sulcus (IPS) and dorsolateral prefrontal cortex, in a recent work by Javadi et al. (2015) , primary motor cortex was also implicated. By applying transcranial direct current stimulation (tDCS), they have revealed a causal role of the primary motor cortex excitability in the induction of response time (RT) differences and decision bias in the form of choice probability. The current study aimed to replicate these recent findings with an experimental design that contained a sham group to increase experimental control and an additional testing phase to investigate the possible after-effects of tDCS. The conventional decision outputs such as choice proportion and RT were analyzed along with the theory-driven estimates of choice bias and non-decision related components of RTs (e.g., motor implementation speed of choices made). None of the statistical comparisons favored the alternative hypotheses over the null hypotheses. Consequently, previous findings regarding the effect of primary motor cortex excitability on choice bias and response times could not be replicated with a more controlled experimental design that is recommended for tDCS studies ( Horvath et al., 2015 ). This empirical discrepancy between the two studies adds to the evidence demonstrating inconsistent effects of tDCS in establishing causal relationships between cortical excitability and motor behavior. [ABSTRACT FROM AUTHOR]

Magnetic stimulation is less sensitive to the inflammatory reactions that plague conventional electrode-based cortical implants and therefore may be useful as a next-generation (implanted) cortical prosthetic. The fields arising from micro-coils are quite small however and thus, their ability to modulate cortical activity must first be established. Here, we show that layer V pyramidal neurons (PNs) can be strongly activated by micro-coil stimulation and further, the asymmetric fields arising from such coils do not simultaneously activate horizontally-oriented axon fibers, thus confining activation to a focal region around the coil. The spatially-narrow fields from micro-coils allowed the sensitivity of different regions within a single PN to be compared: while the proximal axon was most sensitive in naïve cells, repetitive stimulation over the apical dendrite led to a change in state of the neuron that reduced thresholds there to below those of the axon. Thus, our results raise the possibility that regardless of the mode of stimulation, penetration depths that target specific portions of the apical dendrite may actually be more effective than those that target Layer 6. Interestingly, the state change had similar properties to state changes described previously at the systems level, suggesting a possible neuronal mechanism underlying such responses. [ABSTRACT FROM AUTHOR]

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5 ± 25.7 ms; phase 2: the peak at 381.3 ± 28.3 ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1’s first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing. [ABSTRACT FROM AUTHOR]

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments. [ABSTRACT FROM AUTHOR]