The supplementary motor area modulates interhemispheric interactions during movement preparation.
ABSTRACT: The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.
Project description:Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere.
Project description:Youth with Tourette syndrome (TS) exhibit, compared to healthy, abnormal ability to lateralize digital sequential tasks. It is unknown whether this trait is related to inter-hemispheric connections, and whether it is preserved or lost in patients with TS persisting through adult life. We studied 13 adult TS patients and 15 age-matched healthy volunteers. All participants undertook: 1) a finger opposition task, performed with the right hand (RH) only or with both hands, using a sensor-engineered glove in synchrony with a metronome at 2 Hz; we calculated a lateralization index [(single RH-bimanual RH)/single RH X 100) for percentage of correct movements (%CORR); 2) MRI-based diffusion tensor imaging and probabilistic tractography of inter-hemispheric corpus callosum (CC) connections between supplementary motor areas (SMA) and primary motor cortices (M1). We confirmed a significant increase in the %CORR in RH in the bimanual vs. single task in TS patients (p<0.001), coupled to an abnormal ability to lateralize finger movements (significantly lower lateralization index for %CORR in TS patients, p = 0.04). The %CORR lateralization index correlated positively with tic severity measured with the Yale Global Tic Severity Scale (R = 0.55;p = 0.04). We detected a significantly higher fractional anisotropy (FA) in both the M1-M1 (p = 0.036) and the SMA-SMA (p = 0.018) callosal fibre tracts in TS patients. In healthy subjects, the %CORR lateralization index correlated positively with fractional anisotropy of SMA-SMA fibre tracts (R = 0.63, p = 0.02); this correlation was not significant in TS patients. TS patients exhibited an abnormal ability to lateralize finger movements in sequential tasks, which increased in accuracy when the task was performed bimanually. This abnormality persists throughout different age periods and appears dissociated from the transcallosal connectivity of motor cortical regions. The altered interhemispheric transfer of motor abilities in TS may be the result of compensatory processes linked to self-regulation of motor control.
Project description:Visual spatial information is paramount in guiding bimanual coordination, but anatomical factors, too, modulate performance in bimanual tasks. Vision conveys not only abstract spatial information, but also informs about body-related aspects such as posture. Here, we asked whether, accordingly, visual information induces body-related, or merely abstract, perceptual-spatial constraints in bimanual movement guidance. Human participants made rhythmic, symmetrical and parallel, bimanual index finger movements with the hands held in the same or different orientations. Performance was more accurate for symmetrical than parallel movements in all postures, but additionally when homologous muscles were concurrently active, such as when parallel movements were performed with differently rather than identically oriented hands. Thus, both perceptual and anatomical constraints were evident. We manipulated visual feedback with a mirror between the hands, replacing the image of the right with that of the left hand and creating the visual impression of bimanual symmetry independent of the right hand's true movement. Symmetrical mirror feedback impaired parallel, but improved symmetrical bimanual performance compared with regular hand view. Critically, these modulations were independent of hand posture and muscle homology. Thus, visual feedback appears to contribute exclusively to spatial, but not to body-related, anatomical movement coding in the guidance of bimanual coordination.
Project description:Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are well-established tools for investigating the human motor system in-vivo. We here studied the relationship between movement-related fMRI signal changes in the primary motor cortex (M1) and electrophysiological properties of the hand motor area assessed with neuronavigated TMS in 17 healthy subjects. The voxel showing the highest task-related BOLD response in the left hand motor area during right hand movements was identified for each individual subject. This fMRI peak voxel in M1 served as spatial target for coil positioning during neuronavigated TMS. We performed correlation analyses between TMS parameters, BOLD signal estimates and effective connectivity parameters of M1 assessed with dynamic causal modeling (DCM). The results showed a negative correlation between the movement-related BOLD signal in left M1 and resting as well as active motor threshold (MT) obtained for left M1. The DCM analysis revealed that higher excitability of left M1 was associated with a stronger coupling between left supplementary motor area (SMA) and M1. Furthermore, BOLD activity in left M1 correlated with ipsilateral silent period (ISP), i.e. the stronger the task-related BOLD response in left M1, the higher interhemispheric inhibition effects targeting right M1. DCM analyses revealed a positive correlation between the coupling of left SMA with left M1 and the duration of ISP. The data show that TMS parameters assessed for the hand area of M1 do not only reflect the intrinsic properties at the stimulation site but also interactions with remote areas in the human motor system.
Project description:Older adults exhibit more bilateral motor cortical activity during unimanual task performance than young adults. Interestingly, a similar pattern is seen in young adults with reduced hand dominance. However, older adults report stronger hand dominance than young adults, making it unclear how handedness is manifested in the aging motor cortex. Here, we investigated age differences in the relationships between handedness, motor cortical organization, and interhemispheric communication speed. We hypothesized that relationships between these variables would differ for young and older adults, consistent with our recent proposal of an age-related shift in interhemispheric interactions. We mapped motor cortical representations of the right and left first dorsal interosseous muscles using transcranial magnetic stimulation (TMS) in young and older adults recruited to represent a broad range of the handedness spectrum. We also measured interhemispheric communication speed and bimanual coordination. We observed that more strongly handed older adults exhibited more ipsilateral motor activity in response to TMS; this effect was not present in young adults. Furthermore, we found opposing relationships between interhemispheric communication speed and bimanual performance in the two age groups. Thus, handedness manifests itself differently in the motor cortices of young and older adults and has interactive effects with age.
Project description:Whereas the cerebral representation of bimanual spatial coordination has been subject to prior research, the networks mediating bimanual temporal coordination are still unclear. The present study used functional imaging to investigate cerebral networks mediating temporally uncoupled bimanual finger movements. Three bimanual tasks were designed for the execution of movements with different timing and amplitude, with same timing but different amplitude, and with same timing and amplitude. Functional magnetic resonance imaging results showed an increase of activation within right premotor and dorsolateral prefrontal, bilateral inferior parietal, basal ganglia, and cerebellum areas related to temporally uncoupled bilateral finger movements. Further analyses showed a decrease of connectivity between homologous primary hand motor regions. In contrast, there was an increase of connectivity between motor regions and anterior cingulate, premotor and posterior parietal regions during bimanual movements that were spatially or both temporally and spatially uncoupled, compared with bimanual movements that were both spatially and temporally coupled. These results demonstrate that the extent of bihemispheric coupling of M1 areas is related to the degree of temporal synchronization of bimanual finger movements. Furthermore, inferior parietal and premotor regions play a key role for the implementation not only of spatial but also of temporal movement parameters in bimanual coordination.
Project description:The aim of this study was to examine whether older adults use the same task-specific brain activation patterns during two different bimanual hand movement tasks as younger adults. Functional magnetic resonance brain imaging was performed in 18 younger (mean age: 30.3 ± 3.6 years) and 11 older adults (62.6 ± 6.8 years) during the execution of cooperative (mimicking opening a bottle) or non-cooperative (bimanual pro-/supination) hand movements. We expected to see a stronger task-specific involvement of the secondary somatosensory cortex (S2) during cooperative hand movements in older compared to younger adults. However, S2 activation was present in both groups during the cooperative task and was only significantly stronger compared to the non-cooperative task in younger adults. In a whole brain-analysis, the contrast between older and younger adults revealed a hyperactivation of the bilateral dorsal premotor cortex (precentral gyrus), right thalamus, right frontal operculum, anterior cingulate cortex, and supplementary motor areas in older adults (<i>p</i> < 0.001), with some of them being visible after correcting for age. Age was positively associated with fMRI signal changes in these regions across the whole sample. Older adults showed reduced gray matter volume but not in regions showing task-related fMRI group differences. We also found an increase in functional connectivity between SMA, M1, thalamus, and precentral gyri in older adults. In contrast, younger adults showed hyperconnectivity between S2 and S1. We conclude that older compared to younger adults show age-related functional neuroplastic changes in brain regions involved in motor control and performance.
Project description:Congenital mirror movements (CMM) are characterized by involuntary movements of one side of the body that mirror intentional movements on the opposite side. CMM reflect dysfunctions and structural abnormalities of the motor network and are mainly inherited in an autosomal-dominant fashion. Recently, heterozygous mutations in DCC, the gene encoding the receptor for netrin 1 and involved in the guidance of developing axons toward the midline, have been identified but CMM are genetically heterogeneous. By combining genome-wide linkage analysis and exome sequencing, we identified heterozygous mutations introducing premature termination codons in RAD51 in two families with CMM. RAD51 mRNA was significantly downregulated in individuals with CMM resulting from the degradation of the mutated mRNA by nonsense-mediated decay. RAD51 was specifically present in the developing mouse cortex and, more particularly, in a subpopulation of corticospinal axons at the pyramidal decussation. The identification of mutations in RAD51, known for its key role in the repair of DNA double-strand breaks through homologous recombination, in individuals with CMM reveals a totally unexpected role of RAD51 in neurodevelopment. These findings open a new field of investigation for researchers attempting to unravel the molecular pathways underlying bimanual motor control in humans.
Project description:When placing one hand on each side of a mirror and making synchronous bimanual movements, the mirror-reflected hand feels like one's own hand that is hidden behind the mirror. We developed a novel mirror box illusion to investigate whether motoric, but not spatial, visuomotor congruence is sufficient for inducing multisensory integration, and importantly, if biomechanical constraints encoded in the body schema influence multisensory integration. Participants placed their hands in a mirror box in opposite postures (palm up, palm down), creating a conflict between visual and proprioceptive feedback for the hand behind the mirror. After synchronous bimanual hand movements in which the viewed and felt movements were motorically congruent but spatially in the opposite direction, participants felt that the hand behind the mirror rotated or completely flipped towards matching the hand reflection (illusory displacement), indicating facilitation of multisensory integration by motoric visuomotor congruence alone. Some wrist rotations are more difficult due to biomechanical constraints. We predicted that these biomechanical constraints would influence illusion effectiveness, even though the illusion does not involve actual limb movement. As predicted, illusory displacement increased as biomechanical constraints and angular disparity decreased, providing evidence that biomechanical constraints are processed in multisensory integration.
Project description:The control and adaptation of bimanual movements is often considered to be a function of a fixed set of mechanisms [1, 2]. Here, I show that both feedback control and adaptation change optimally with task goals. Participants reached with two hands to two separate spatial targets (two-cursor condition) or used the same bimanual movements to move a cursor presented at the spatial average location of the two hands to a single target (one-cursor condition). A force field was randomly applied to one of the hands. In the two-cursor condition, online corrections occurred only on the perturbed hand, whereas the other movement was controlled independently. In the one-cursor condition, online correction could be detected on both hands as early as 190 ms after the start. These changes can be shown to be optimal in respect to a simple task-dependent cost function . Adaptation, the influence of a perturbation onto the next movement, also depended on task goals. In the two-cursor condition, only the perturbed hand adapted to a force perturbation , whereas in the one-cursor condition, both hands adapted. These findings demonstrate that the central nervous system changes bimanual feedback control and adaptation optimally according to the current task requirements.