Ipsilateral M1 Research Articles

Time course of the effects of low-intensity transcranial ultrasound on the excitability of ipsilateral and contralateral human primary motor cortex

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

Increased Ipsilateral M1 Activation after Incomplete Spinal Cord Injury Facilitates Motor Performance.

Incomplete spinal cord injury (SCI) may result in muscle weakness and difficulties with force gradation. Although these impairments arise from the injury and subsequent changes at spinal levels, changes have also been demonstrated in the brain. Blood-oxygen-level dependent (BOLD) imaging was used to investigate these changes in brain activation in the context of unimanual contractions with the first dorsal interosseous muscle. BOLD- and force data were obtained in 19 individuals with SCI (AISA Impairment Scale [AIS] C/D, level C4-C8) and 24 able-bodied controls during maximal voluntary contractions (MVCs). To assess force modulation, participants performed 12 submaximal contractions with each hand (at 10, 30, 50, and 70% MVC) by matching their force level to a visual target. MVCs were weaker in the SCI group (both hands p < 0.001), but BOLD activation did not differ between SCI and control groups. For the submaximal contractions, force (as %MVC) was similar across groups. However, SCI participants showed increased activity of the ipsilateral motor cortex and contralateral cerebellum across all contractions, with no differential effect of force level. Activity of ipsilateral M1 was best explained by force of the target hand (vs. the non-target hand). In conclusion, the data suggest that after incomplete cervical SCI, individuals remain capable of producing maximal supraspinal drive and are able to modulate this drive adequately. Activity of the ipsilateral motor network appears to be task related, although it remains uncertain how this activity contributes to task performance and whether this effect could potentially be harnessed to improve motor functioning.

A single session of submaximal grip strength training with or without high-definition anodal-TDCS produces no cross-education of maximal force

BACKGROUND: Previous studies suggest that cross-education of strength may be modulated by increased corticospinal excitability of the ipsilateral primary motor cortex (M1) due to cross-activation. However, no study has examined the influence of bilateral TDCS of both M1 and how it affects corticospinal excitability, cross-activation and cross-education of muscle strength. METHOD: Twelve participants underwent three conditions in a randomized crossover design: (1) submaximal grip training and single-site unilateral-high definition-TDCS (2) submaximal grip training and bilateral anodal-high definition-TDCS, and (3) submaximal grip training and sham-high definition-TDCS. Submaximal gripping task involved a single-session of unilateral training which was squeezing the transducer at 70% of maximum voluntary isometric contraction (MVIC) grip force and performing four sets of 10 isometric contractions. Anodal-high definition-TDCS was applied for 15 min at 1.5 mA over right M1 or left and right M1s, and in a sham condition. Participants were pseudorandomized to receive either single-site or bilateral M1 stimulation with each session separated by one-week. Before and after each session, MVIC force of ipsilateral and contralateral gripping, ipsilateral stimulus-response curve, short-interval intracortical inhibition, cortical silent period, intracortical facilitation, long-interval intracortical inhibition, and cross-activation were measured. RESULTS: MVIC of the trained arm decreased by 43% (P=0.04) after training. We observed no changes in MVIC of the untrained hand and in any of the TMS measures (all P&gt;0.05). CONCLUSION: A single session of submaximal grip training with or without anodal-high definition-TDCS produces no cross-education of maximal grip force nor does it affect the excitability of the ipsilateral M1.

Ageing and the Ipsilateral M1 BOLD Response: A Connectivity Study.

Young people exhibit a negative BOLD response in ipsilateral primary motor cortex (M1) when making unilateral movements, such as button presses. This negative BOLD response becomes more positive as people age. In this study, we investigated why this occurs, in terms of the underlying effective connectivity and haemodynamics. We applied dynamic causal modeling (DCM) to task fMRI data from 635 participants aged 18–88 from the Cam-CAN dataset, who performed a cued button pressing task with their right hand. We found that connectivity from contralateral supplementary motor area (SMA) and dorsal premotor cortex (PMd) to ipsilateral M1 became more positive with age, explaining 44% of the variability across people in ipsilateral M1 responses. In contrast, connectivity from contralateral M1 to ipsilateral M1 was weaker and did not correlate with individual differences in rM1 BOLD. Neurovascular and haemodynamic parameters in the model were not able to explain the age-related shift to positive BOLD. Our results add to a body of evidence implicating neural, rather than vascular factors as the predominant cause of negative BOLD—while emphasising the importance of inter-hemispheric connectivity. This study provides a foundation for investigating the clinical and lifestyle factors that determine the sign and amplitude of the M1 BOLD response in ageing, which could serve as a proxy for neural and vascular health, via the underlying neurovascular mechanisms.

Existence of Interhemispheric Inhibition between Foot Sections of Human Primary Motor Cortices: Evidence from Negative Blood Oxygenation-Level Dependent Signal.

Interhemispheric inhibition (IHI) between the left and right primary motor cortices (M1) plays an important role when people perform an isolated unilateral limb movement. Moreover, negative blood oxygenation-level dependent signal (deactivation) obtained from the M1 ipsilateral to the limb could be a surrogate IHI marker. Studies have reported deactivation in the hand section of the ipsilateral M1 during simple unilateral hand movement. However, deactivation in the foot section during unilateral foot movement has not been reported. Therefore, IHI between the foot sections of the bilateral M1s has been considered very weak or absent. Thirty-seven healthy adults performed active control of the right foot and also passively received vibration to the tendon of the tibialis anterior muscle of the right foot, which activates the foot section of the contralateral M1, with brain activity being examined through functional magnetic resonance imaging. The vibration and active tasks significantly and non-significantly, respectively, deactivated the foot section of the ipsilateral M1, with a corresponding 86% and 60% of the participants showing decreased activity. Thus, there could be IHI between the foot sections of the bilateral M1s. Further, our findings demonstrate between-task differences and similarities in cross-somatotopic deactivation.

Mechanical thrombectomy in acute ischemic stroke with tandem occlusions: impact of extracranial carotid lesion etiology on endovascular management and outcome.

Different etiologies of extracranial internal carotid artery steno-occlusive lesions (ECLs) in patients with acute ischemic stroke (AIS) and tandem occlusion (TO) have been pooled together in randomized trials. However, carotid atherosclerosis (CA) and carotid dissection (CD), the two most common ECL etiologies, are distinct nosological entities. The authors aimed to determine if ECL etiology has impacts on the endovascular management and outcome of patients with TO. A multicenter, retrospective study of prospectively collected data was conducted. AIS patients were included who had TO due to internal CA or CD and ipsilateral M1 middle cerebral artery occlusion and underwent endovascular treatment (EVT). Comparative analyses including demographic data, safety, successful recanalization rates, and clinical outcome were performed according to EVT and ECL etiology. In total, 214 AIS patients with TOs were included (77.6% CA related, 22.4% CD related). Patients treated with a retrograde approach were more often functionally independent at 3 months than patients treated with an antegrade approach (OR 0.6, 95% CI 0.4-0.9). Patients with CD-related TOs achieved 90-day clinical independence more often than patients with CA-related TOs (OR 1.4, 95% CI 1.1-2.0). Emergency stenting use was associated with good 3-month clinical outcome only in patients with CA-related TOs (OR 1.4, 95% CI 1.1-2.1). Symptomatic intracranial hemorrhage (sICH) occurred in 10.7% of patients, without differences associated with ECL etiology. ECL etiology impacts both EVT approach and clinical outcome in patients with TOs. Patients with CD-related TO achieved higher 3-month functional independence rates than patients with CA-related TOs. A retrograde approach can be desirable for both CA- and CD-related TOs, and emergency stenting is likely better justified in CA-related TOs.

Motor Cortex Activation During Writing in Focal Upper-Limb Dystonia: An fNIRS Study

Background Functional imaging studies have associated dystonia with abnormal activation in motor and sensory brain regions. Commonly used techniques such as functional magnetic resonance imaging impose physical constraints, limiting the experimental paradigms. Functional near-infrared spectroscopy (fNIRS) offers a new noninvasive possibility for investigating cortical areas and the neural correlates of complex motor behaviors in unconstrained settings. Methods We compared the cortical brain activation of patients with focal upper-limb dystonia and controls during the writing task under naturalistic conditions using fNIRS. The primary motor cortex (M1), the primary somatosensory cortex (S1), and the supplementary motor area were chosen as regions of interest (ROIs) to assess differences in changes in both oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) between groups. Results Group average activation maps revealed an expected pattern of contralateral recruitment of motor and somatosensory cortices in the control group and a more bilateral pattern of activation in the dystonia group. Between-group comparisons focused on specific ROIs revealed an increased activation of the contralateral M1 and S1 cortices and also of the ipsilateral M1 cortex in patients. Conclusions Overactivity of contralateral M1 and S1 in dystonia suggest a reduced specificity of the task-related cortical areas, whereas ipsilateral activation possibly indicates a primary disorder of the motor cortex or an endophenotypic pattern. To our knowledge, this is the first study using fNIRS to assess cortical activity in dystonia during the writing task under natural settings, outlining the potential of this technique for monitoring sensory and motor retraining in dystonia rehabilitation.

Reduced Facilitation of Parietal-Motor Functional Connections in Older Adults.

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.

Characterizing hemodynamic response alterations during basketball dribbling.

Knowledge on neural processing during complex non-stationary motion sequences of sport-specific movements still remains elusive. Hence, we aimed at investigating hemodynamic response alterations during a basketball slalom dribbling task (BSDT) using multi-distance functional near-infrared spectroscopy (fNIRS) in 23 participants (12 females). Additionally, we quantified how the brain adapts its processing as a function of altered hand use (dominant right hand (DH) vs. non-dominant left hand (NDH) vs. alternating hands (AH)) and pace of execution (slow vs. fast) in BSDT. We found that BSDT activated bilateral premotor cortex (PMC), supplementary motor cortex (SMA), primary motor cortex (M1) as well as inferior parietal cortex and somatosensory association cortex. Slow dominant hand dribbling (DHslow) evoked lower contralateral hemodynamic responses in sensorimotor regions compared to fast dribbling (DHfast). Furthermore, during DHslow dribbling, we found lower hemodynamic responses in ipsilateral M1 as compared to dribbling with alternating hands (AHslow). Hence, altered task complexity during BSDT induced differential hemodynamic response patterns. Furthermore, a correlation analysis revealed that lower levels of perceived task complexity are associated with lower hemodynamic responses in ipsilateral PMC-SMA, which is an indicator for neuronal efficiency in participants with better basketball dribbling skills. The present study extends previous findings by showing that varying levels of task complexity are reflected by specific hemodynamic response alterations even during sports-relevant motor behavior. Taken together, we suggest that quantifying brain activation during complex movements is a prerequisite for assessing brain-behavior relations and optimizing motor performance.

Is bilateral corticospinal connectivity impaired in patients with chronic obstructive pulmonary disease?

During moderate and high levels of quadriceps force production, the ipsilateral motor cortex is concomitantly activated with the contralateral motor cortex throughout the corpus callosum to generate the motor command. Chronic obstructive pulmonary disease (COPD) patients display a structurally impaired corpus callosum that may explain the reduced motor command in this population, which in turn contributes to COPD-related muscle weakness of the knee extensors. The study aimed to determine whether bilateral connectivity was impaired and ipsilateral activation was lowered during unilateral strength production of the knee extensors. Our results indicate impaired bilateral connectivity but preserved ipsilateral activation in patients during unilateral isometric contractions of 50% of maximum voluntary strength. The preservation of ipsilateral activation during force production despite impaired bilateral connectivity is consistent with a reorganization of bilateral motor network function that drives unilateral strength production. The contralateral primary motor cortex (M1) is not the only brain area implicated in motor command generation. During moderate and high levels of quadriceps force production, the ipsilateral M1 is concomitantly activated. Such activation is mediated by the corpus callosum, the main component of bilateral connectivity. Structural damage to the corpus callosum has been observed in chronic obstructive pulmonary disease (COPD) patients, which might reduce ipsilateral activation and contribute to the lower motor command associated with COPD muscle weakness. We thus aimed to determine whether bilateral connectivity and ipsilateral activation were impaired in COPD. Twenty-two COPD patients and 21 healthy age-matched controls were evaluated by transcranial magnetic stimulation, at rest and during 50% of maximal voluntary isometric contraction (MVIC) of the dominant vastus lateralis muscle. Bilateral connectivity was determined by the ipsilateral silent period (iSP) during 50% MVIC. Ipsilateral activation was determined as the increase in ipsilateral excitability from rest to 50% MVIC. As expected, COPD patients had significantly lower MVIC (-25%, p=0.03). These patients also showed a significantly lower iSP (-53%, p<0.001) compared to controls. The ipsilateral excitability was increased in patients and controls (×2.5 and ×3.5, respectively, p<0.001) but not differently between groups (p=0.84). Despite impaired bilateral connectivity in COPD, ipsilateral activation was not increased. Reorganization in the patients' interhemispheric pathways could explain the preserved ipsilateral activation.

Importance of the Primary Motor Cortex in Development of Human Hand/Finger Dexterity.

Hand/finger dexterity is well-developed in humans, and the primary motor cortex (M1) is believed to play a particularly important role in it. Here, we show that efficient recruitment of the contralateral M1 and neuronal inhibition of the ipsilateral M1 identified by simple hand motor and proprioceptive tasks are related to hand/finger dexterity and its ontogenetic development. We recruited healthy, right-handed children (n = 21, aged 8–11 years) and adults (n = 23, aged 20–26 years) and measured their brain activity using functional magnetic resonance imaging during active and passive right-hand extension–flexion tasks. We calculated individual active control-related activity (active–passive) to evaluate efficient brain activity recruitment and individual task-related deactivation (neuronal inhibition) during both tasks. Outside the scanner, participants performed 2 right-hand dexterous motor tasks, and we calculated the hand/finger dexterity index (HDI) based on their individual performance. Participants with a higher HDI exhibited less active control-related activity in the contralateral M1 defined by the active and passive tasks, independent of age. Only children with a higher HDI exhibited greater ipsilateral M1 deactivation identified by these tasks. The results imply that hand/finger dexterity can be predicted by recruitment and inhibition styles of the M1 during simple hand sensory–motor tasks.

Primary motor cortical activity during unimanual movements with increasing demand on precision.

In functional magnetic resonance imaging (fMRI) studies, performance of unilateral hand movements is associated with primary motor cortex activity ipsilateral to the moving hand (M1ipsi), in addition to contralateral activity (M1contra). The magnitude of M1ipsi activity increases with the demand on precision of the task. However, it is unclear how demand-dependent increases in M1ipsi recruitment relate to the control of hand movements. To address this question, we used fMRI to measure blood oxygenation level-dependent (BOLD) activity during performance of a task that varied in demand on precision. Participants (n = 23) manipulated an MRI-compatible joystick with their right or left hand to move a cursor into targets of different sizes (small, medium, large, extra large). Performance accuracy, movement time, and number of velocity peaks scaled with target size, whereas reaction time, maximum velocity, and initial direction error did not. In the univariate analysis, BOLD activation in M1contra and M1ipsi was higher for movements to smaller targets. Representational similarity analysis, corrected for mean activity differences, revealed multivoxel BOLD activity patterns during movements to small targets were most similar to those for medium targets and least similar to those for extra-large targets. Only models that varied with demand (target size, performance accuracy, and number of velocity peaks) correlated with the BOLD dissimilarity patterns, though differently for right and left hands. Across individuals, M1contra and M1ipsi similarity patterns correlated with each other. Together, these results suggest that increasing demand on precision in a unimanual motor task increases M1 activity and modulates M1 activity patterns.NEW & NOTEWORTHY Contralateral primary motor cortex (M1) predominantly controls unilateral hand movements, but the role of ipsilateral M1 is unclear. We used functional magnetic resonance imaging (fMRI) to investigate how M1 activity is modulated by unimanual movements at different levels of demand on precision. Our results show that task characteristics related to demand on precision influence bilateral M1 activity, suggesting that in addition to contralateral M1, ipsilateral M1 plays a key role in controlling hand movements to meet performance precision requirements.

Hemispheric Differences in Functional Interactions Between the Dorsal Lateral Prefrontal Cortex and Ipsilateral Motor Cortex.

Background: The dorsolateral prefrontal cortex (DLPFC) in both hemispheres have a central integrative function for motor control and behavior. Understanding the hemispheric difference between DLPFC and ipsilateral motor cortex connection in the resting-state will provide fundamental knowledge to explain the different roles DLPFC plays in motor behavior.Purpose: The current study tested the interactions between the ipsilateral DLPFC and the primary motor cortex (M1) in each hemisphere at rest. We hypothesized that left DLPFC has a greater inhibitory effect on the ipsilateral M1 compared to the right DLPFC.Methods: Fourteen right-handed subjects were tested in a dual-coil paired-pulse paradigm using transcranial magnetic stimulation. The conditioning stimulus (CS) was applied to the DLPFC and the test stimulus (TS) was applied to M1. Interstimulus intervals (ISIs) between CS and TS were 2, 4, 6, 8, 10, 15, 20, 25, and 30 ms. The result was expressed as a percentage of the mean peak-to-peak amplitude of the unconditioned test pulse.Results: There was stronger inhibitory effect for the left compared to the right hemisphere at ISIs of 2 (p = 0.045), 10 (p = 0.006), 15 (p = 0.029) and 20 (p = 0.024) ms. There was no significant inhibition or facilitation at any ISI in the right hemisphere.Conclusions: The two hemispheres have distinct DLPFC and M1 cortico-cortical connectivity at rest. Left hemisphere DLPFC is dominant in inhibiting ipsilateral M1.

Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis.

Objective: We employed dual-site TMS to test whether ipsilateral functional premotor-motor connectivity is altered in relapsing-remitting Multiple Sclerosis (RR-MS) and is related to central fatigue.Methods: Twelve patients with RR-MS and 12 healthy controls performed a visually cued Pinch-NoPinch task with their right hand. During the reaction time (RT) period of Pinch and No-Pinch trials, single-site TMS was applied to the left primary motor cortex (M1) or dual-site TMS was applied to the ipsilateral dorsal premotor cortex (PMd) and to M1. We traced context-dependent changes of corticospinal excitability and premotor–motor connectivity by measuring Motor-Evoked Potentials (MEPs) in the right first dorsal interosseus muscle. Central fatigue was evaluated with the Fatigue Scale for Motor and Cognitive Functions (FSMS).Results: In both groups, single-pulse TMS revealed a consistent increase in mean MEP amplitude during the Reaction Time (RT) period relative to a resting condition. Task-related corticospinal facilitation increased toward the end of the RT period in Pinch trials, while it decreased in No-Pinch trials. Again, this modulation of MEP facilitation by trial type was comparable in patients and controls. Dual-site TMS showed no significant effect of a conditioning PMd pulse on ipsilateral corticospinal excitability during the RT period in either group. However, patients showed a trend toward a relative attenuation in functional PMd-M1 connectivity at the end of the RT period in No-Pinch trials, which correlated positively with the severity of motor fatigue (r = 0.69; p = 0.007).Conclusions: Dynamic regulation of corticospinal excitability and ipsilateral PMd-M1 connectivity is preserved in patients with RR-MS. MS-related fatigue scales positively with an attenuation of premotor-to-motor functional connectivity during cued motor inhibition.Significance: The temporal, context-dependent modulation of ipsilateral premotor-motor connectivity, as revealed by dual-site TMS of ipsilateral PMd and M1, constitutes a promising neurophysiological marker of fatigue in MS.

Implication of the ipsilateral motor network in unilateral voluntary muscle contraction: the cross-activation phenomenon.

Voluntary force production requires that the brain produces and transmits a motor command to the muscles. It is widely acknowledged that motor commands are executed from the primary motor cortex (M1) located in the contralateral hemisphere. However, involvement of M1 located in the ipsilateral hemisphere during moderate to high levels of unilateral muscle contractions (>30% of the maximum) has been disclosed in recent years. This phenomenon has been termed cross-activation. The activation of the ipsilateral M1 relies on complex inhibitory and excitatory interhemispheric interactions mediated via the corpus callosum and modulated according to the contraction level. The regulatory mechanisms underlying these interhemispheric interactions, especially excitatory ones, remain vague, and contradictions exist in the literature. In addition, very little is known regarding the possibility that other pathways could also mediate the cross-activation. In the present review, we will therefore summarize the concept of cross-activation during unilateral voluntary muscle contraction and explore the associated mechanisms and other nervous system pathways underpinning this response. A broader knowledge of these mechanisms would consequently allow a better comprehension of the motor system as a whole, as distant brain networks working together to produce the motor command.

Role of kinaesthetic motor imagery in mirror-induced visual illusion as intervention in post-stroke rehabilitation.

Mirror-induced visual illusion obtained through mirror therapy is widely used to facilitate motor recovery after stroke. Activation of primary motor cortex (M1) ipsilateral to the moving limb has been reported during mirror-induced visual illusion. However, the mechanism through which the mirror illusion elicits motor execution processes without movements observed in the mirrored limb remains unclear. This study aims to review evidence based on brain imaging studies for testing the hypothesis that neural processes associated with kinaesthetic motor imagery are attributed to ipsilateral M1 activation. Four electronic databases were searched. Studies on functional brain imaging, investigating the instant effects of mirror-induced visual illusion among stroke survivors and healthy participants were included. Thirty-five studies engaging 78 stroke survivors and 396 healthy participants were reviewed. Results of functional brain scans (n = 20) indicated that half of the studies (n = 10, 50%) reported significant changes in the activation of ipsilateral M1, which mediates motor preparation and execution. Other common neural substrates included primary somatosensory cortex (45%, kinaesthesia), precuneus (40%, image generation and self-processing operations) and cerebellum (20%, motor control). Similar patterns of ipsilateral M1 activations were observed in the two groups. These neural substrates mediated the generation, maintenance, and manipulation of motor-related images, which were the key processes in kinaesthetic motor imagery. Relationships in terms of shared neural substrates and mental processes between mirror-induced visual illusion and kinaesthetic motor imagery generate new evidence on the role of the latter in mirror therapy. Future studies should investigate the imagery processes in illusion training for post-stroke patients.

Converging sensory and motor cortical inputs onto the same striatal neurons: An in vivo intracellular investigation

The striatum is involved in the completion and optimization of sensorimotor tasks. In rodents, its dorsolateral part receives converging glutamatergic corticostriatal (CS) inputs from whisker-related primary somatosensory (S1) and motor (M1) cortical areas, which are interconnected at the cortical level. Although it has been demonstrated that the medium-spiny neurons (MSNs) from the dorsolateral striatum process sensory information from the whiskers via the S1 CS pathway, the functional impact of the corresponding M1 CS inputs onto the same striatal neurons remained unknown. Here, by combining in vivo S1 electrocorticogram with intracellular recordings from somatosensory MSNs in the rat, we first confirmed the heterogeneity of striatal responsiveness to whisker stimuli, encompassing MSNs responding exclusively by subthreshold synaptic depolarizations, MSNs exhibiting sub- and suprathreshold responses over successive stimulations, and non-responding cells. All recorded MSNs also exhibited clear-cut monosynaptic depolarizing potentials in response to electrical stimulations of the corresponding ipsilateral M1 cortex, which were efficient to fire striatal cells. Since M1-evoked responses in MSNs could result from the intra-cortical recruitment of S1 CS neurons, we performed intracellular recordings of S1 pyramidal neurons and compared their firing latency following M1 stimuli to the latency of striatal synaptic responses. We found that the onset of M1-evoked synaptic responses in MSNs significantly preceded the firing of S1 neurons, demonstrating a direct synaptic excitation of MSNs by M1. However, the firing of MSNs seemed to require the combined excitatory effects of S1 and M1 CS inputs. This study directly demonstrates that the same somatosensory MSNs can process excitatory synaptic inputs from two functionally-related sensory and motor cortical regions converging into the same striatal sector. The effectiveness of these convergent cortical inputs in eliciting action potentials in MSNs may represent a key mechanism of striatum-related sensorimotor behaviors.

Exercise Plus Pharmacological Neuromodulation of Synaptic Inhibition Enhance Motor Function Recovery After Ischemic Stroke

The objective of this study was to examine the interactive effects of exercise and low-level inhibition of GABAA receptors on the recovery of motor function and BDNF expression in the primary motor cortex (M1) of a stroke rat model. Male Sprague–Dawley rats were divided into five groups: sham (SHAM), control (CON), exercise (EX), bicuculline (BIC), and bicuculline plus exercise (BICEX) groups. All rats, except those in the SHAM group, underwent middle cerebral artery occlusion (MCAO) surgery to induce an ischemic stroke. GABAA receptor antagonist, bicuculline (0.25 mg/kg, i.p.), was administered to the BIC and BICEX groups. The EX and BICEX groups exercised on a treadmill (11 m/min for 30 min). Each intervention started 3 days after the MCAO surgery and was carried out every day for 2 weeks. Following the intervention, bilateral M1 BDNF mRNA and protein expression levels were assessed using qRT-PCR and ELISA. Marginal recovery was found in the EX and BIC groups, whereas motor function recovery was enhanced with exercise in the presence of BIC administration specifically in the BICEX group. Furthermore, BDNF protein level in the ipsilateral M1 was significantly higher in the BICEX group than in other groups. This study indicated that exercise combined with low-level inhibition of GABAA receptors after stroke could facilitate the recovery of motor function accompanied by BDNF upregulation in the ipsilateral M1. Therefore, this study provides a novel insight of pharmacological neuromodulation into stroke rehabilitation.

Ipsilateral primary motor cortex and behavioral compensation after stroke: a case series study.

Arm motor recovery after stroke is mainly attributed to reorganization of the primary motor cortex (M1). While M1 contralateral to the paretic arm (cM1) is critical for recovery, the role of ipsilateral M1 (iM1) is still inconclusive. Whether iM1 activity is related to recovery, behavioral compensation, or both is still far from settled. We hypothesized that the magnitude of iM1 activity in chronic stroke survivors will increase ordecrease in direct proportion to the degree that movements of the paretic arm are compensated. Movement kinematics (VICON, Oxford Metrics) and functional MRI data (3T MR system) were collected in 11 patients before and after a 4-week training designed to improve motor control of the paretic arm and decrease compensatory trunk recruitment. Twelve matched controls underwent similar evaluations and training. Relationships between iM1 activity and trunk motion were analyzed. At baseline, patients exhibited increased iM1 activity (p = 0.001) and relied more on trunk movement (p = 0.02) than controls. These two variables were directly and significantly related in patients (r = 0.74, p = 0.01) but not in controls (r = 0.28, p = 0.4). After training, patients displayed a significant reduction in iM1 activity (p = 0.008) and a trend toward decreased trunk use (p = 0.1). The relationship between these two variables remained significant (r = 0.66, p = 0.03) and different from controls (r = 0.26, p = 0.4). Our preliminary results suggest that iM1 may play a role in compensating for brain damage rather than directly gaining control of the paretic arm. However, we recommend caution in interpreting these results until more work is completed.

Age affects the contribution of ipsilateral brain regions to movement kinematics.

Healthy aging is accompanied by changes in brain activation patterns in the motor system. In older subjects, unilateral hand movements typically rely on increased recruitment of ipsilateral frontoparietal areas. While the two central concepts of aging‐related brain activity changes, “Hemispheric Asymmetry Reduction in Older Adults” (HAROLD), and “Posterior to Anterior Shift in Aging” (PASA), have initially been suggested in the context of cognitive tasks and were attributed to compensation, current knowledge regarding the functional significance of increased motor system activity remains scarce. We, therefore, used online interference transcranial magnetic stimulation in young and older subjects to investigate the role of key regions of the ipsilateral frontoparietal cortex, that is, (a) primary motor cortex (M1), (b) dorsal premotor cortex (dPMC), and (c) anterior intraparietal sulcus (IPS) in the control of hand movements of different motor demands. Our data suggest a change of the functional roles of ipsilateral brain areas in healthy age with a reduced relevance of ipsilateral M1 and a shift of importance toward dPMC for repetitive high‐frequency movements. These results support the notion that mechanisms conceptualized in the models of “PASA” and “HAROLD” also apply to the motor system.