Jolien Gooijers

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.

Bimanual coordination and corpus callosum microstructure in young adults with traumatic brain injury: a diffusion tensor imaging study

Bimanual actions are ubiquitous in daily life. Many coordinated movements of the upper extremities rely on precise timing, which requires efficient interhemispheric communication via the corpus callosum (CC). As the CC in particular is known to be vulnerable to traumatic brain injury (TBI), furthering our understanding of its structure-function association is highly valuable for TBI diagnostics and prognosis. In this study, 21 young adults with TBI and 17 controls performed object manipulation tasks (insertion of pegs with both hands and bilateral daily life activities) and cognitive control tasks (i.e., switching maneuvers during spatially and temporally coupled bimanual circular motions). The structural organization of 7 specific subregions of the CC (prefrontal, premotor/supplementary motor, primary motor, primary sensory, parietal, temporal, and occipital) was subsequently investigated in these subjects with diffusion tensor imaging (DTI). Findings revealed that bimanual coordination was impaired in TBI patients as shown by elevated movement time values during daily life activities, a decreased number of peg insertions, and slower response times during the switching task. Furthermore, the DTI analysis demonstrated a significantly decreased fractional anisotropy and increased radial diffusivity in prefrontal, primary sensory, and parietal regions in TBI patients versus controls. Finally, multiple regression analyses showed evidence of the high specificity of callosal subregions accounting for the variance associated with performance of the different bimanual coordination tasks. Whereas disruption in commissural pathways between occipital areas played a role in performance on the clinical tests of bimanual coordination, deficits in the switching task were related to disrupted interhemispheric communication in prefrontal, sensory, and parietal regions. This study provides evidence that structural alterations of several subregional callosal fibers in adults with TBI are associated with differential behavioral manifestations of bimanual motor functioning.

Interactions between brain structure and behavior: the corpus callosum and bimanual coordination

Bimanual coordination skills are required for countless everyday activities, such as typing, preparing food, and driving. The corpus callosum (CC) is the major collection of white matter bundles connecting both hemispheres that enables the coordination between the two sides of the body. Principal evidence for this brain-behavior relationship in humans was first provided by research on callosotomy patients, showing that sectioning (parts of) the CC affected interactions between both hands directly. Later, new noninvasive in vivo imaging techniques, such as diffusion tensor imaging, have energized the study of the link between microstructural properties of the CC and bimanual performance in normal volunteers. Here we discuss the principal factors (such as age, pathology and training) that mediate the relationship between specific bimanual functions and distinct anatomical CC subdivisions. More specifically, the question is whether different bimanual task characteristics can be mapped onto functionally distinct CC subregions. We review the current status of this mapping endeavor, and propose future perspectives to inspire research on this unique link between brain structure and behavior.

Diffusion tensor imaging metrics of the corpus callosum in relation to bimanual coordination: Effect of task complexity and sensory feedback

When manipulating objects with both hands, the corpus callosum (CC) is of paramount importance for interhemispheric information exchange. Hence, CC damage results in impaired bimanual performance. Here, healthy young adults performed a complex bimanual dial rotation task with or without augmented visual feedback and according to five interhand frequency ratios (1:1, 1:3, 2:3, 3:1, 3:2). The relation between bimanual task performance and microstructural properties of seven CC subregions (i.e., prefrontal, premotor/supplementary motor, primary motor, primary sensory, occipital, parietal, and temporal) was studied by means of diffusion tensor imaging (DTI). Findings revealed that bimanual coordination deteriorated in the absence as compared to the presence of augmented visual feedback. Simple frequency ratios (1:1) were performed better than the multifrequency ratios (non 1:1). Moreover, performance was more accurate when the preferred hand (1:3–2:3) as compared to the nonpreferred hand (3:1–3:2) moved faster and during noninteger (2:3–3:2) as compared to integer frequency ratios (1:3–3:1). DTI findings demonstrated that bimanual task performance in the absence of augmented visual feedback was significantly related to the microstructural properties of the primary motor and occipital region of the CC, suggesting that white matter microstructure is associated with the ability to perform bimanual coordination patterns in young adults. Hum Brain Mapp, 2013.

Microstructural organization of corpus callosum projections to prefrontal cortex predicts bimanual motor learning

The corpus callosum (CC) is the largest white matter tract in the brain. It enables interhemispheric communication, particularly with respect to bimanual coordination. Here, we use diffusion tensor imaging (DTI) in healthy humans to determine the extent to which structural organization of subregions within the CC would predict how well subjects learn a novel bimanual task. A single DTI scan was taken prior to training. Participants then practiced a bimanual visuomotor task over the course of 2 wk, consisting of multiple coordination patterns. Findings revealed that the predictive power of fractional anisotropy (FA) was a function of CC subregion and practice. That is, FA of the anterior CC, which projects to the prefrontal cortex, predicted bimanual learning rather than the middle CC regions, which connect primary motor cortex. This correlation was specific in that FA correlated significantly with performance of the most difficult frequency ratios tested and not the innately preferred, isochronous frequency ratio. Moreover, the effect was only evident after training and not at initiation of practice. This is the first DTI study in healthy adults which demonstrates that white matter organization of the interhemispheric connections between the prefrontal structures is strongly correlated with motor learning capability.

Testing Multiple Coordination Constraints with a Novel Bimanual Visuomotor Task

The acquisition of a new bimanual skill depends on several motor coordination constraints. To date, coordination constraints have often been tested relatively independently of one another, particularly with respect to isofrequency and multifrequency rhythms. Here, we used a new paradigm to test the interaction of multiple coordination constraints. Coordination constraints that were tested included temporal complexity, directionality, muscle grouping, and hand dominance. Twenty-two healthy young adults performed a bimanual dial rotation task that required left and right hand coordination to track a moving target on a computer monitor. Two groups were compared, either with or without four days of practice with augmented visual feedback. Four directional patterns were tested such that both hands moved either rightward (clockwise), leftward (counterclockwise), inward or outward relative to each other. Seven frequency ratios (3∶1, 2∶1, 3∶2, 1∶1, 2∶3. 1∶2, 1∶3) between the left and right hand were introduced. As expected, isofrequency patterns (1∶1) were performed more successfully than multifrequency patterns (non 1∶1). In addition, performance was more accurate when participants were required to move faster with the dominant right hand (1∶3, 1∶2 and 2∶3) than with the non-dominant left hand (3∶1, 2∶1, 3∶2). Interestingly, performance deteriorated as the relative angular velocity between the two hands increased, regardless of whether the required frequency ratio was an integer or non-integer. This contrasted with previous finger tapping research where the integer ratios generally led to less error than the non-integer ratios. We suggest that this is due to the different movement topologies that are required of each paradigm. Overall, we found that this visuomotor task was useful for testing the interaction of multiple coordination constraints as well as the release from these constraints with practice in the presence of augmented visual feedback.

Reduced Neural Differentiation Between Feedback Conditions After Bimanual Coordination Training with and without Augmented Visual Feedback

It has been established that bimanual coordination with augmented feedback (FB) versus no augmented feedback (NFB) is associated with activity in different brain regions. It is unclear however, whether this distinction remains after practice comprising both these conditions. Functional magnetic resonance imaging was used in humans to compare visual FB versus NFB conditions for a bimanual tracking task, and their differential evolution across learning. Scanning occurred before (Pre) and after 2 weeks (Post) of mixed FB and NFB training using an event-related design, allowing differentiation between the planning and execution phase of the task. Activations at the whole-brain level initially differed for FB versus NFB movements but this differentiation diminished with training for the movement execution phase. Specifically, in right dorsal premotor cortex and right dorsolateral prefrontal cortex activation increased for NFB and decreased for FB trials to converge toward the end of practice. This suggests that learning led to a decreased need to adjust the ongoing movement on the basis of FB, whereas online monitoring became more pronounced in NFB trials as discrepancies between the required and the produced motor output were detected more accurately after training, due to a generic internal reference of correctness supporting movement control under varying conditions.

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. SIGNIFICANCE STATEMENT The structural and functional changes in the aging brain are associated with a decline in movement control, compromising functional independence. We used MRI and noninvasive brain stimulation techniques to investigate white matter microstructural organization and neurophysiological function in the aging brain, in relation to bimanual movement control. We found that less optimal brain microstructural organization and task-related modulations in neurophysiological function resulted in poor bimanual performance in older adults. By interrelating brain structure, neurophysiological function, and behavior, the current study provides a comprehensive picture of biological alterations in the aging brain that underlie declines in bimanual performance.

Two hands, one brain, and aging

HIGHLIGHTSAging makes bimanual coordination performance more cognition‐dependent.Hyper and hypo‐activity in the aging brain may interact to determine performance.Higher resting‐state connectivity is associated with lower performance in olders.Task‐related connectivity increases with higher task demand irrespective of age. ABSTRACT Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well‐being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper‐activity (but also subcortical hypo‐activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age‐related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults.

Subcortical Volume Loss in the Thalamus, Putamen, and Pallidum, Induced by Traumatic Brain Injury, Is Associated With Motor Performance Deficits

Background. Traumatic brain injury (TBI) has been associated with altered microstructural organization of white matter (WM) and reduced gray matter (GM). Although disrupted WM organization has been linked to poorer motor performance, the predictive value of GM atrophy for motor impairments in TBI remains unclear. Objective. Here, we investigated TBI-induced GM volumetric abnormalities and uniquely examined their relationship with bimanual motor impairments. Methods. 22 moderate to severe TBI patients (mean age = 25.9 years, standard deviation [SD] = 4.9 years; time since injury = 4.7 years, SD = 3.7 years) and 27 age- and gender-matched controls (mean age = 23.4 years; SD = 3.8 years) completed bimanual tasks and a structural magnetic resonance imaging scan. Cortical and subcortical GM volumes were extracted and compared between groups using FreeSurfer. The association between bimanual performance and GM volumetric measures was investigated using partial correlations. Results. Relative to controls, patients performed significantly poorer on the bimanual tasks and demonstrated significantly smaller total GM as well as overall and regional subcortical GM. However, the groups did not show significant differences in regional cortical GM volume. The majority of the results remained significant even after excluding TBI patients with focal lesions, suggesting that TBI-induced volume reductions were predominantly caused by diffuse injury. Importantly, atrophy of the thalamus, putamen, and pallidum correlated significantly with poorer bimanual performance within the TBI group. Conclusions. Our results reveal that GM atrophy is associated with motor impairments in TBI, providing new insights into the etiology of motor control impairments following brain trauma.