Age-Related Changes in Frontal Network Structural and Functional Connectivity in Relation to Bimanual Movement Control

Changes in both brain structure and neurophysiological function regulating homotopic as well as heterotopic interhemispheric interactions (IHIs) are assumed to be responsible for the bimanual performance deficits in older adults. However, how the structural and functional networks regulating bimanual performance decline in older adults, as well as the interplay between brain structure and function remain largely unclear. Using a dual-site transcranial magnetic stimulation paradigm, we examined the age-related changes in the interhemispheric effects from the dorsolateral prefrontal cortex and dorsal premotor cortex onto the contralateral primary motor cortex (M1) during the preparation of a complex bimanual coordination task in human. Structural properties of these interactions were assessed with diffusion-based fiber tractography. Compared with young adults, older adults showed performance declines in the more difficult bimanual conditions, less optimal brain white matter (WM) microstructure, and a decreased ability to regulate the interaction between dorsolateral prefrontal cortex and M1. Importantly, we found that WM microstructure, neurophysiological function, and bimanual performance were interrelated in older adults, whereas only the task-related changes in IHI predicted bimanual performance in young adults. These results reflect unique interactions between structure and function in the aging brain, such that declines in WM microstructural organization likely lead to dysfunctional regulation of IHI, ultimately accounting for bimanual performance deficits

Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration

Zebrafish hearts can regenerate by replacing damaged tissue with new cardiomyocytes. Although the steps leading up to the proliferation of surviving cardiomyocytes have been extensively studied, little is known about the mechanisms that control proliferation and redifferentiation to a mature state. We found that the cardiac dyad, a structure that regulates calcium handling and excitation-contraction coupling, played a key role in the redifferentiation process. A component of the cardiac dyad called leucine-rich repeat-containing 10 (Lrrc10) acted as a negative regulator of proliferation, prevented cardiomegaly, and induced redifferentiation. We found that its function was conserved in mammalian cardiomyocytes. This study highlights the importance of the underlying mechanisms required for heart regeneration and their application to the generation of fully functional cardiomyocytes.Microbial Biotechnolog

Altered structural networks and executive deficits in traumatic brain injury patients

Recent research on traumatic brain injury (TBI) has shown that impairments in cognitive and executive control functions are accompanied by a disrupted neural connectivity characterized by white matter damage. We constructed binary and weighted brain structural networks in 21 patients with chronic TBI and 17 healthy young adults utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. Executive function was assessed with the local global task and the trail making task, requiring inhibition, updating, and switching. The results revealed that TBI patients were less successful than controls on the executive tasks, as shown by the higher reaction times, higher switch costs, and lower accuracy rates. Moreover, both TBI patients and controls exhibited a small world topology in their white matter networks. More importantly, the TBI patients demonstrated increased shortest path length and decreased global efficiency of the structural network. These findings suggest that TBI patients have a weaker globally integrated structural brain network, resulting in a limited capacity to integrate information across brain regions. Furthermore, we showed that the white matter networks of both groups contained highly connected hub regions that were predominately located in the parietal cortex, frontal cortex, and basal ganglia. Finally, we showed significant correlations between switching performance and network property metrics within the TBI group. Specifically, lower scores on the switching tasks corresponded to a lower global efficiency. We conclude that analyzing the structural brain network connectivity provides new insights into understanding cognitive control changes following brain injury

Representational Similarity Scores of Digits in the Sensorimotor Cortex Are Associated with Behavioral Performance

Previous studies aimed to unravel a digit-specific somatotopy in the primary sensorimotor (SM1) cortex. However, it remains unknown whether digit somatotopy is associated with motor preparation and/or motor execution during different types of tasks. We adopted multivariate representational similarity analysis to explore digit activation patterns in response to a finger tapping task (FTT). Sixteen healthy young adults underwent magnetic resonance imaging, and additionally performed an out-of-scanner choice reaction time task (CRTT) to assess digit selection performance. During both the FTT and CRTT, force data of all digits were acquired using force transducers. This allowed us to assess execution-related interference (i.e., digit enslavement; obtained from FTT & CRTT), as well as planning-related interference (i.e., digit selection deficit; obtained from CRTT) and determine their correlation with digit representational similarity scores of SM1. Findings revealed that digit enslavement during FTT was associated with contralateral SM1 representational similarity scores. During the CRTT, digit enslavement of both hands was also associated with representational similarity scores of the contralateral SM1. In addition, right hand digit selection performance was associated with representational similarity scores of left S1. In conclusion, we demonstrate a cortical origin of digit enslavement, and uniquely reveal that digit selection is associated with digit representations in primary somatosensory cortex (S1). Significance statement In current systems neuroscience, it is of critical importance to understand the relationship between brain function and behavioral outcome. With the present work, we contribute significantly to this understanding by uniquely assessing how digit representations in the sensorimotor cortex are associated with planning- and execution-related digit interference during a continuous finger tapping and a choice reaction time task. We observe that digit enslavement (i.e., execution-related interference) finds its origin in contralateral digit representations of SM1, and that deficits in digit selection (i.e., planning-related interference) in the right hand during a choice reaction time task are associated with more overlapping digit representations in left S1. This knowledge sheds new light on the functional contribution of the sensorimotor cortex to everyday motor skills

White matter organization in relation to upper limb motor control in healthy subjects: exploring the added value of diffusion kurtosis imaging

Diffusion tensor imaging (DTI) characterizes white matter (WM) microstructure. In many brain regions, however, the assumption that the diffusion probability distribution is Gaussian may be invalid, even at low b values. Recently, diffusion kurtosis imaging (DKI) was suggested to more accurately estimate this distribution. We explored the added value of DKI in studying the relation between WM microstructure and upper limb coordination in healthy controls (N = 24). Performance on a complex bimanual tracking task was studied with respect to the conventional DTI measures (DKI or DTI derived) and kurtosis metrics of WM tracts/regions carrying efferent (motor) output from the brain, corpus callosum (CC) substructures and whole brain WM. For both estimation models, motor performance was associated with fractional anisotropy (FA) of the CC-genu, CC-body, the anterior limb of the internal capsule, and whole brain WM (rs range 0.42–0.63). Although DKI revealed higher mean, radial and axial diffusivity and lower FA than DTI (p < 0.001), the correlation coefficients were comparable. Finally, better motor performance was associated with increased mean and radial kurtosis and kurtosis anisotropy (rs range 0.43–0.55). In conclusion, DKI provided additional information, but did not show increased sensitivity to detect relations between WM microstructure and bimanual performance in healthy controls

Different neural substrates for precision stepping and fast online step adjustments in youth

Contains fulltext : 193602.pdf (publisher's version ) (Open Access)Humans can navigate through challenging environments (e.g., cluttered or uneven terrains) by modifying their preferred gait pattern (e.g., step length, step width, or speed). Growing behavioral and neuroimaging evidence suggests that the ability to modify preferred step patterns requires the recruitment of cognitive resources. In children, it is argued that prolonged development of complex gait is related to the ongoing development of involved brain regions, but this has not been directly investigated yet. Here, we aimed to elucidate the relationship between structural brain properties and complex gait in youth aged 9-18 years. We used volumetric analyses of cortical grey matter (GM) and whole-brain voxelwise statistical analyses of white matter (WM), and utilized a treadmill-based precision stepping task to investigate complex gait. Moreover, precision stepping was performed on step targets which were either unperturbed or perturbed (i.e., unexpectedly shifting to a new location). Our main findings revealed that larger unperturbed precision step error was associated with decreased WM microstructural organization of tracts that are particularly associated with attentional and visual processing functions. These results strengthen the hypothesis that precision stepping on unperturbed step targets is driven by cortical processes. In contrast, no significant correlations were found between perturbed precision stepping and cortical structures, indicating that other (neural) mechanisms may be more important for this type of stepping

Indices of callosal axonal density and radius from diffusion MRI relate to upper and lower limb motor performance

Understanding the relationship between human brain structure and functional outcome is of critical importance in systems neuroscience. Diffusion MRI (dMRI) studies show that fractional anisotropy (FA) is predictive of motor control, underscoring the importance of white matter (WM). However, as FA is a surrogate marker of WM, we aim to shed new light on the structural underpinnings of this relationship by applying a multi-compartment microstructure model providing axonal density/radius indices. Sixteen young adults (7 males / 9 females), performed a hand/foot tapping task and a Multi Limb Reaction Time task. Furthermore, diffusion (STEAM &HARDI) and fMRI (localizer hand/foot activations) data were obtained. Sphere ROIs were placed on activation clusters with highest t value to guide interhemispheric WM tractography. Axonal radius/density indices of callosal parts intersecting with tractography were calculated from STEAM, using the diffusion-time dependent AxCaliber model, and correlated with behavior. Results indicated a possible association between larger apparent axonal radii of callosal motor fibers of the hand and higher tapping scores of both hands, and faster selection-related processing (normalized reaction) times (RTs) on diagonal limb combinations. Additionally, a trend was present for faster selection-related processing (normalized reaction) times for lower limbs being related with higher axonal density of callosal foot motor fibers, and for higher FA values of callosal motor fibers in general being related with better tapping and faster selection-related processing (normalized reaction) times. Whereas FA is sensitive in demonstrating associations with motor behavior, axon radius/density (i.e., fiber geometry) measures are promising to explain the physiological source behind the observed FA changes, contributing to deeper insights into brain-behavior interactions

Bimanual motor deficits in older adults predicted by diffusion tensor imaging metrics of corpus callosum subregions

Age-related changes in the microstructural organization of the corpus callosum (CC) may explain declines in bimanual motor performance associated with normal aging. We used diffusion tensor imaging in young (n = 33) and older (n = 33) adults to investigate the microstructural organization of seven specific CC subregions (prefrontal, premotor, primary motor, primary sensory, parietal, temporal and occipital). A set of bimanual tasks was used to assess various aspects of bimanual motor functioning: the Purdue Pegboard test, simultaneous and alternating finger tapping, a choice reaction time test and a complex visuomotor tracking task. The older adults showed age-related deficits on all measures of bimanual motor performance. Correlation analyses within the older group showed that white matter fractional anisotropy of the CC occipital region was associated with bimanual fine manipulation skills (Purdue Pegboard test), whereas better performance on the other bimanual tasks was related to higher fractional anisotropy in the more anterior premotor, primary motor and primary sensory CC subregions. Such associations were less prominent in the younger group. Our findings suggest that structural alterations of subregional callosal fibers may account for bimanual motor declines in normal aging