A computational model based on corticospinal functional MRI revealed asymmetrically organized motor corticospinal networks in humans

新規MRI技術で利き手の神経制御メカニズムを解明 --手指運動中の脳・脊髄機能結合パターンの左右差を世界で初めて計測--. 京都大学プレスリリース. 2022-08-08.Evolution of the direct, monosynaptic connection from the primary motor cortex to the spinal cord parallels acquisition of hand dexterity and lateralization of hand preference. In non-human mammals, the indirect, multi-synaptic connections between the bilateral primary motor cortices and the spinal cord also participates in controlling dexterous hand movement. However, it remains unknown how the direct and indirect corticospinal pathways work in concert to control unilateral hand movement with lateralized preference in humans. Here we demonstrated the asymmetric functional organization of the two corticospinal networks, by combining network modelling and simultaneous functional magnetic resonance imaging techniques of the brain and the spinal cord. Moreover, we also found that the degree of the involvement of the two corticospinal networks paralleled lateralization of hand preference. The present results pointed to the functionally lateralized motor nervous system that underlies the behavioral asymmetry of handedness in humans

Upper Limb Asymmetries of Movement Sense and Sense of Effort: The Contribution of Gender and Handedness.

Asymmetry in upper limb performances may have multiple origins. The aim of this research is to determine the contribution of sensory and motor processes to asymmetries in movement sense and sense of effort when considering gender and handedness. The distinction between gender and handedness effects, while often ignored, may shed new light on human performances. The first study investigated asymmetry in movement sense using contralateral reproductions of vibration induced illusions of movements in right (RH) and left (LH) handed young adults of both genders. Females were found more sensitive to vibratory stimulations and less asymmetric than males in movement reproduction. The asymmetry observed in males was related to handedness. Both asymmetry and sensitivity were primarily sensory in origin. The second study investigated asymmetries in the sense of effort and targeted the motor component. Both RH and LH adults were divided into three groups based on hand strength differences. A 20% MVC reference grip force was matched with the same or opposite hand (of the reference). The matching error increased with hand strength differences for RH only, suggesting that the sense of effort is a consequence of both muscle strength differences and an intrinsic asymmetry of the motor component that may vary with handedness. The last study investigated the relative contributions of efferent copy and sensory feedback to the sense of effort. Vibration was used to distort the sensory information from muscles providing the reference in the grip matching task. Visual feedback of the reference hand was also manipulated. The hand/hemisphere systems were found to differ significantly in their dependence on proprioceptive information during force reproduction, with the left hand being more feedback dependent. These findings lead us to suggest that hand preference and gender contribute to differences in movement representation, force production and sense of effort that may result from the combination of cortical structural differences and information processing specific to each hemisphere, gender and handedness group.PhDIndustrial & Operations EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99857/1/sscotlan_1.pd

Speech lateralization and motor control

A relationship between motor control and speech lateralization has long been postulated by researchers and clinicians with an interest in the functional organization of the human brain. Exactly how motor control might be related to speech representation, however, is rarely examined. This chapter examines current issues relating to the organization, development and measurement of motor control and speech representation. We further consider from neuropsychological, developmental, neurological and genetic perspectives that speech and fine motor control involve planning and sequencing processes, which are mediated by an integrated neural network localized to the left hemisphere. Specifically, we discuss studies from our laboratory using functional Transcranial Doppler ultrasonography to determine speech laterality, correlating this with hand preference and pegboard measures of motor laterality. Our findings show that handedness, as measured by a motor skill task, can be predictive of speech laterality, both in typically developing adults and children. We have also shown that individuals with developmental motor coordination impairments also show atypical speech lateralization, providing further evidence that neurological motor and speech systems are intrinsically connected. We consider these results in the context of a left lateralized speech-praxis center model, which could account for the relationship shown between sequenced-based motor and speech tasks

Does Handedness for Prehension Predict Handedness for Role-Differentiated Bimanual Manipulation During Infancy?

The clearly observable behaviors that identify infant hand-use preferences make the development of this sensorimotor form of lateralization a valuable model for evaluating the development of other forms of lateral asymmetries of function. The current study examined the relation of individual patterns of development of handedness for reaching for objects (prehension) to the emergence of handedness in role-differentiated bimanual manipulation (RDBM). RDBM requires each hand to perform different, but complementary, actions on one or more objects. Hand-use reference for reaching for and grasping objects was assessed in a sample of 85 infants from the period of 6- to 11-months of age using a validated handedness assessment that consists of a series of presentations of 34 common infant toys. At 11 and 14 months, hand-use preferences for RDBM were assessed while the infants were involved in semiplay activity in which they were presented with a series of 13 toys (20-40 s for each presentation). Results revealed no significant relationship between prehension handedness and handedness for RDBM. However, multi-level modeling of the prehension data revealed interesting developmental changes in prehension handedness that can only be identified by using monthly sampling intervals with longitudinal methods

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition

Cerebral lateralisation of speech production and motor skill

The association between praxis and language is longstanding in neuropsychology, with evidence revealing that left hemisphere lesions often lead to combined impairments in motor control and speech (Rasmussen and Milner, 1975; Goldenberg, 2013). Strong left hemisphere asymmetry for language is a robust finding at the population level (e.g. Knecht et al 2000a) and similarly the cortical activation patterns of manual praxis for skilled tasks also reveal a left hemisphere bias (Buxbaum et al, 2005; Haaland et al, 2004). As such, common neural mechanisms are thought to underlie both speech and motor skill, especially actions involving fine motor control of the hands. However, evidence for a clear causal relationship between handedness and speech laterality has proven somewhat weak and inconsistent, due to the wide variation in measurement and classification approaches used (Groen, et al, 2013). A suggestion by Flowers and Hudson (2013) is that motor and speech laterality are related where they involve a common feature of motor output, namely the co-ordination of sequences of movements or utterances to execute a plan or intention so as to achieve a goal; either limb movement or expression of an idea (e.g. Grimme, et al, 2011). The research conducted here investigates speech and motor lateralisation from the hypothesis that sequencing based tasks will be best able to elicit the predicted left hemisphere activation patterns. Five empirical chapters are presented detailing a number of studies involving healthy adults, typically developing children and adults with Developmental Coordination Disorder. The research uses an emerging technique in cognitive neuropsychology; functional Transcranial Doppler (fTCD) sonography, to explore hemispheric laterality of speech and motor skill. Measurements of the degree of activation in each of the hemispheres during language tasks, and the use of a skill-based motor task to determine handedness, are the primary indicators of lateralisation used throughout this thesis. Results from the first 3 chapters 4 reveal that 1) atypical patterns of speech laterality are linked to greater performance differences on motor skill tasks; 2) that whilst hand preference is established early on in childhood the relative performance ability between the non-preferred and preferred hands develops linearly with age; 3) adults with developmental coordination disorder display atypical patterns of laterality of speech networks. The final 2 empirical chapters employ novel neuroimaging paradigms to investigate the mechanisms underlying the links between speech and motor sequencing. Results show that the pegboard task elicits left hemisphere dominant activation regardless of the hand used, unlike other motor tasks with similar properties. Finally a dual task paradigm demonstrates that speech production suffers greater impairments than motor skill when performed simultaneously, providing support for theories proposing a gestural origin to speech. The data are discussed in terms of the specialisation of the left hemisphere for higher order sequential processing, in the context of a lateralised speech-praxis centre model

Hand immobilization causes changes in cortical areas: qEEG alpha band absolute power study

Hand immobilization has been associated with changes in neural networks of primary somatosensory cortex and primary motor areas. Electrophysiologically, alpha band absolute power may indicate how cerebral cortex processes information. This study aimed to analyze changes in alpha band absolute power on frontal, central, parietal and occipital derivations when hand-movement of subjects was restricted for 48 hours. Fifteen healthy volunteers (20 to 30 years old), were recorded using electroencephalography (qEEG), while exposition to visual stimulus linked to a motor task before and after hand immobilization. Statistical analysis revealed that hand immobilization caused changes in frontal, central and parietal areas of cerebral cortex. In summary, after hand immobilization alpha band absolute power increased in these areas, revealing a lower activation. Contrarily, at C4 there was a decreased alpha band absolute power correlated to more activation. These findings can be due adaptive plasticity to supply less activation at C3, considering the inactivity of right hand due to the immobilization. Further studies are needed to better understand the complex processes involved in this type of task

Bilateral upper-limb coordination in aging and stroke

Bilateral upper-limb coordination is an important ability for our living independency, since most of our daily tasks, such as lifting a box or using knife and fork, require the simultaneous use of both arms (Waller et al., 2006). However, bilateral coordination decline has been observed in both healthy aging and neurological groups (Pollock et al., 2014; Maes et al., 2017) , which often results in decreased quality of life (Broeks et al., 1999; Franceschini et al., 2010). Therefore, this dissertation sought to understand the characteristics and mechanisms of bilateral coordination and its impairments. The two fundamental bilateral movements in human upper limbs, i.e., in-phase (homologous muscles from bilateral arms activate simultaneously) and anti-phase (different muscle groups from bilateral arms activate simultaneously) movements, have been found to show different characteristics in behavioral and neural measurements (Swinnen and Wenderoth, 2004). Behaviorally, anti-phase movements are found to be performed with lower movement accuracy and higher phase variability between hands compared to in-phase movements (Wuyts et al., 1996; Byblow et al., 2000; Pollok et al., 2007). On the neural level, fMRI studies demonstrated that the left hemisphere shows larger task-related BOLD signal changes compared to the right hemisphere during in-phase movements (Aramaki et al., 2006), while the BOLD signal changes between the two hemispheres are similar during anti-phase movements (Walsh et al., 2008). These results suggest a left-dominated control of in-phase movements. However, a critical limitation in the literature is the lack of causal evidence supporting hemispherical specialization in bilateral coordination. Therefore, it is unclear whether the observed behavioral differences between anti-phase and in-phase movements were truly due to distinct hemispheric control. Another limitation of the literature is the design of existing paradigms. While most of our daily activities involve movements engaging multiple joints at the same time (Keenan et al., 2006; Murphy et al., 2006), previous studies mostly investigated single joint movements (e.g. index finger tapping, forearm pronation-supination). Contrary to single joint movements, bilateral movements engaging multiple joints require not only inter-limb coordination, but also additional intra-limb coordination. Therefore, it is unclear whether the previous findings from single joint movements could be directly applied to multiple joint movements. In this dissertation, we used a bilateral coordination paradigm involving both shoulder and elbow joints to investigate the neural mechanisms behind bilateral coordination and its decline. We designed three studies focusing on 1) the differences between bilateral in-phase and anti-phase movements from a human motion perspective, 2) how aging affects different bilateral coordination patterns and its neural correlates, as well as 3) how lesioned hemisphere affects bilateral coordination impairments and whether distinct rehabilitation treatments are needed after a left or right hemispheric stroke. In Study 1, we examined the two basic bilateral coordination modes, in-phase and anti-phase movements, in healthy young right-handed participants. We used a bilateral circle drawing task involving both shoulder and elbow joints. During the movements, we measured participants’ hand positions with high temporal and spatial precision, and developed intra-limb and inter-limb measures to differentiate movement characteristics during the two basic movement modes. For intra-limb coordination, we quantified trajectory variability of each hand during the movements. For inter-limb coordination, we computed the phase synchronization between hands. We found that intra-limb coordination was worse in the non-dominant hand during anti-phase compared to in-phase movements. In contrast, intra-limb coordination in the dominant hand did not differ between anti-phase and in-phase movements. Second, participants showed worse inter-limb synchronization during anti-phase compared to in-phase movements. Moreover, we examined the hand acceleration profile of both hands, and found that participants’ bilateral hands accelerated and decelerated in an in-phase manner during in-phase movements. In contrast, the acceleration and deceleration of the two hands were unrelated during anti-phase movements. These inter-limb acceleration profiles support the idea of differential neural mechanisms behind bilateral anti-phase and in-phase movements: during in-phase movements, the hands are governed by a common neural generator, while during anti-phase movements, the two hands are controlled by both hemispheres more independently. Taken together, Study 1 showed that the current experimental setup is able to differentiate the performance between bilateral in-phase and anti-phase movements engaging multiple joints. Therefore, we used the same paradigm combined with electroencephalography (EEG) to examine the presumed decline of bilateral coordination in aging. In Study 2, we investigated the effect of aging on the two basic bilateral movement modes. We used intra- and inter-limb measures as the behavioral measures, and EEG as a neural measure. Behaviorally, we found that older adults only showed significant impairments in anti-phase movements, but not in-phase movements, compared to young adults. On the neural level, we found that older adults showed different neural responses during anti-phase and in-phase movements compared to young adults. Specifically, during in-phase movements, young adults showed a more pronounced decrease of alpha power (8-12 Hz) over the left compared to the right hemisphere, while older adults showed similar levels of alpha power decrease over both hemispheres. Furthermore, in the older adults, we found a marginal correlation between the change in alpha power over the right hemisphere and the behavioral performance, which indicated a compensatory brain response. As for the anti-phase movements, we found that participants with stronger directional inter-hemispheric connectivity in the beta band (15-25 Hz) showed worse behavioral performance, and this effect was more pronounced in the older adults. This result implies that a balanced inter-hemispheric contribution is essential for executing a successful anti-phase movement. Our findings therefore show that the two hemispheres are differentially involved in the two basic bilateral coordination modes. These different neural characteristics may explain the distinct decline patterns of in-phase and anti-phase movements in older adults. However, causal evidence to support hemispherical specialization is needed to confirm our findings. Therefore, we conducted Study 3, where we used stroke as a lesion model to examine the influence of the lesioned hemisphere on bilateral coordination. In Study 3, we examined the bilateral coordination ability in patients with left (LHS) and right hemispheric stroke (RHS), as well as healthy controls. Given that healthy young participants show a left-dominant control in in-phase movements in Study 2 and in the previous literature (Aramaki et al., 2006; Maki et al., 2008), we expected that LHS patients would display a more pronounced impairment of in-phase movements compared to RHS patients. In contrast, since anti-phase movements require a more balanced inter-hemispheric contribution as shown in Study 2, and RHS patients show larger inter-hemispheric inhibition compared to healthy participants and LHS patients (Lewis and Perreault, 2007b), we expected that RHS patients would show more impairment in anti-phase movements compared to LHS patients. As predicted, we found that patients with RHS patients exhibited greater impairment during anti-phase movements (both intra- and inter-limb parameters) and LHS patients showed greater impairment during in-phase movements (intra-limb parameters only). Though LHS patients did not show greater impairment in inter-limb coordination during in-phase movements compared to RHS patients, our regression analysis revealed that only LHS patients swapped hand dominance during the task. We interpreted this result as a compensatory mechanism whereby bilateral in-phase movements in the LHS group switched from a left-dominated cortical control to a right-dominated cortical control. Our findings not only provide causal evidence for hemispheric specialization in bilateral movement coordination, but also characterize the differential impairments in bilateral coordination after a left or right hemispheric stroke. Taken together, this dissertation highlighted differential neural control processes involved in bilateral in-phase and anti-phase movements, and demonstrated how these distinct mechanisms lead to impaired bilateral coordination in aging and stroke. The present results could therefore advance the development of therapeutic strategies that seek to counteract bilateral coordination decline, such as differential treatment for patients with left and right hemispheric lesions, or the use of noninvasive brain stimulation at a target hemisphere.:List of abbreviations List of figures List of tables Chapter 1. General introduction 1.1. Introduction 1.2. Bilateral coordination in human upper extremities 1.3. Age-related motor decline 1.4. Stroke-induced motor impairments Chapter 2. Rationale of the Dissertation Chapter 3. Study I: Human motion characteristics during bilateral in-phase and anti-phase movements 3.1. Introduction 3.2. Materials and methods 3.3. Results 3.4. Discussion 3.5. Conclusion Chapter 4. Study II: The effect of aging on bilateral coordination 49 4.1. Introduction 4.2. Materials and methods 4.3. Results 4.4. Discussion 4.5. Conclusion Chapter 5. Study III: Effects of lesioned side on bilateral coordination after strokes 5.1. Introduction 5.2. Materials and methods 5.3. Results 5.4. Discussion 5.5. Conclusion Chapter 6. General discussion 6.1. Summary of research 6.2. Contributions and clinical implications 6.3. Outlook for future research Chapter 7. Summary of the dissertation References Appendix Appendix 1. Supplementary information for study 1 Appendix 2. Supplementary information for study 2 Appendix 3. Supplementary information for study 3 Appendix 4. Declaration of authenticit

The relationship between lateralization patterns from sequence based motor tasks and hemispheric speech dominance

Objective: Skilled motor praxis and speech production display marked asymmetries at the individual and the population level, favouring the right hand and the left hemisphere respectively. Theories suggesting a common processing mechanism between praxis and speech are supported by evidence that shared neural architecture underlies both functions. Despite advances in understanding the neurobiology of this left-hemisphere specialisation the cortical networks linking these two functions are rarely investigated on a behavioural level. Method: This study deploys functional Transcranial Doppler (fTCD) ultrasound to directly measure hemispheric activation during skilled manual praxis tasks shown to be correlated to hemispheric speech lateralisation indices. In a new paradigm we test the hypothesis that praxis tasks are highly dependent on the left hemisphere's capacity for processing sequential information will be better correlated with direction and strength of hemispheric speech lateralisation Results: Across two experiments we firstly show that only certain praxis tasks (pegboard and coin-rotation) correlated with direct measurements of speech lateralisation despite shared properties across all tasks tested. Secondly, through novel imaging of hemispheric activation during praxis, results showed that the pegboard differed in the lateralisation pattern created and furthermore that it was significantly related to speech laterality indices, which was not the case for either of the other two tasks. Conclusion: These results are discussed in terms of a lateralised speech-praxis control mechanism and demonstrates that measurements of motor paradigms through the use of fTCD are reliable enough to provide a new insight to the behavioural relationship been speech and handedness