David Drijkoningen

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.

Brain connectivity and postural control in young traumatic brain injury patients: A diffusion MRI based network analysis.

Our previous research on traumatic brain injury (TBI) patients has shown a strong relationship between specific white matter (WM) diffusion properties and motor deficits. The potential impact of TBI-related changes in network organization of the associated WM structural network on motor performance, however, remains largely unknown. Here, we used diffusion tensor imaging (DTI) based fiber tractography to reconstruct the human brain WM networks of 12 TBI and 17 control participants, followed by a graph theoretical analysis. A force platform was used to measure changes in body posture under conditions of compromised proprioceptive and/or visual feedback. Findings revealed that compared with controls, TBI patients showed higher betweenness centrality and normalized path length, and lower values of local efficiency, implying altered network organization. These results were not merely a consequence of differences in number of connections. In particular, TBI patients displayed reduced structural connectivity in frontal, parieto-premotor, visual, subcortical, and temporal areas. In addition, the decreased connectivity degree was significantly associated with poorer balance performance. We conclude that analyzing the structural brain networks with a graph theoretical approach provides new insights into motor control deficits following brain injury.

Training-induced improvements in postural control are accompanied by alterations in cerebellar white matter in brain injured patients

We investigated whether balance control in young TBI patients can be promoted by an 8-week balance training program and whether this is associated with neuroplastic alterations in brain structure. The cerebellum and cerebellar peduncles were selected as regions of interest because of their importance in postural control as well as their vulnerability to brain injury. Young patients with moderate to severe TBI and typically developing (TD) subjects participated in balance training using PC-based portable balancers with storage of training data and real-time visual feedback. An additional control group of TD subjects did not attend balance training. Mean diffusivity and fractional anisotropy were determined with diffusion MRI scans and were acquired before, during (4 weeks) and at completion of training (8 weeks) together with balance assessments on the EquiTest® System (NeuroCom) which included the Sensory Organization Test, Rhythmic Weight Shift and Limits of Stability protocols. Following training, TBI patients showed significant improvements on all EquiTest protocols, as well as a significant increase in mean diffusivity in the inferior cerebellar peduncle. Moreover, in both training groups, diffusion metrics in the cerebellum and/or cerebellar peduncles at baseline were predictive of the amount of performance increase after training. Finally, amount of training-induced improvement on the Rhythmic Weight Shift test in TBI patients was positively correlated with amount of change in fractional anisotropy in the inferior cerebellar peduncle. This suggests that training-induced plastic changes in balance control are associated with alterations in the cerebellar white matter microstructure in TBI patients.

Associations between Muscle Strength Asymmetry and Impairments in Gait and Posture in Young Brain-Injured Patients

Traumatic brain injury (TBI) can lead to deficits in gait and posture, which are often asymmetric. A possible factor mediating these deficits may be asymmetry in strength of the leg muscles. However, muscle strength in the lower extremities has rarely been investigated in (young) TBI patients. Here, we investigated associations between lower-extremity muscle weakness, strength asymmetry, and impairments in gait and posture in young TBI patients. A group of young patients with moderate-to-severe TBI (n=19; age, 14 years 11 months ±2 years) and a group of typically developing subjects (n=31; age, 14 years 1 month±3 years) participated in this study. A force platform was used to measure postural sway to quantify balance control during normal standing and during conditions of compromised visual and/or somatosensory feedback. Spatiotemporal gait parameters were assessed during comfortable and fast-speed walking, using an electronic walkway. Muscle strength in four lower-extremity muscle groups was measured bilaterally using a handheld dynamometer. Findings revealed that TBI patients had poorer postural balance scores across all sensory conditions, as compared to typically developing subjects. During comfortable and fast gait, TBI patients demonstrated a lower gait velocity, longer double-support phase, and increased step-length asymmetry. Further, TBI patients had a reduced strength of leg muscles and an increased strength asymmetry. Correlation analyses revealed that asymmetry in muscle strength was predictive of a poorer balance control and a more variable and asymmetric gait. To the best of our knowledge, this is the first study to measure strength asymmetry in leg muscles of a sample of TBI patients and illustrate the importance of muscular asymmetry as a potential marker and possible risk factor of impairments in control of posture and gait.

Enhanced pre-frontal functional-structural networks to support postural control deficits after traumatic brain injury in a pediatric population

Traumatic brain injury (TBI) affects structural connectivity, triggering the reorganization of structural–functional circuits in a manner that remains poorly understood. We focus here on brain network reorganization in relation to postural control deficits after TBI. We enrolled young participants who had suffered moderate to severe TBI, comparing them to young, typically developing control participants. TBI patients (but not controls) recruited prefrontal regions to interact with two separated networks: (1) a subcortical network, including parts of the motor network, basal ganglia, cerebellum, hippocampus, amygdala, posterior cingulate gyrus, and precuneus; and (2) a task-positive network, involving regions of the dorsal attention system, together with dorsolateral and ventrolateral prefrontal regions. We also found that the increased prefrontal connectivity in TBI patients was correlated with some postural control indices, such as the amount of body sway, whereby patients with worse balance increased their connectivity in frontal regions more strongly. The increased prefrontal connectivity found in TBI patients may provide the structural scaffolding for stronger cognitive control of certain behavioral functions, consistent with the observations that various motor tasks are performed less automatically following TBI and that more cognitive control is associated with such actions. Author Summary Using a new hierarchical atlas whose modules are relevant for both structure and function, we found increased structural and functional connectivity in prefrontal regions in TBI patients as compared to controls, in addition to a general pattern of overall decreased connectivity across the TBI brain. Although this increased prefrontal connectivity reflected interactions between brain areas when participants were at rest, the enhanced connectivity was found to be negatively correlated with active behavior such as postural control performance. Thus our findings, obtained when the brain was at rest, potentially reflect how TBI patients orchestrate task-related activations to support behavior in everyday life. In particular, our findings of enhanced connectivity in TBI might help these patients overcome deficits in cerebellar and subcortical connections, in addition to compensating for deficits when interacting with the task-positive network. Hence, it appears that greater cognitive control is exerted over certain actions in order to overcome deficits in their automatic processing.

Regional Gray Matter Volume Loss Is Associated with Gait Impairments in Young Brain-Injured Individuals

Traumatic brain injury (TBI) often leads to impairments in gait performance. However, the underlying neurostructural pathology of these gait deficits is poorly understood. We aimed to investigate regional gray matter (GM) volume in young moderate-to-severe TBI participants (n = 19; age 13 years 11 months ±3 years 1 month), compared with typically developing (TD) participants (n = 30; 14 years 10 months ±2 years 2 months), and assess whether reduced volume was related to impaired gait performance in TBI participants. Cortical and subcortical GM structures involved in the neural control of gait were selected as regions of interest (ROIs) and their volume was extracted using Freesurfer. Moreover, established spatiotemporal markers of gait impairments in TBI participants, including step length asymmetry, step length variability, and double support time, were obtained using an electronic walkway. Compared with TD participants, TBI participants showed increased double support time, step length asymmetry, and step length variability, suggesting a reduced gait control. Secondly, in TBI participants, reduced volumes were demonstrated in overall subcortical GM and individual subcortical ROIs, including the hippocampus, cerebellar cortex, putamen, and thalamus. Moreover, in the TBI group, volume losses in subcortical ROIs were highly inter-correlated, indicating that atrophy tends to occur in combined subcortical structures. Finally, it was demonstrated, for the first time, that gait abnormalities in TBI subjects were associated with reduced volume in specific GM structures, including the hippocampus, thalamus, and the cerebellar, superior frontal, paracentral, posterior cingulate, and superior parietal cortices. The present study is an important first step in the understanding of the neurostructural pathology underlying impaired gait in TBI patients.

Enhanced pre-frontal functional-structural networks to support behavioural deficits after traumatic brain injury

Traumatic brain injury (TBI) affects its structural connectivity, triggering the re-organization of structural-functional circuits in a manner that remains poorly understood. We studied the re-organization of brain networks after TBI, taking advantage of a computational method based on magnetic resonance imaging (MRI) including diffusion-weighted imaging in combination with functional resting state data obtained from the blood-oxygenation-level-dependent T2* signal. We enrolled young participants who had suffered moderate to severe TBI (N=14, age 13.14 ± 3.25 years), comparing them to young typically developing control participants (N=27, age 15.04 ± 2.26 years). We found increased functional and structural connectivity within a cortico-subcortical network in TBI patient’s brains that involved prefrontal cortex, anterior cingulate gyrus, orbital gyrus and caudate nucleus. In comparison to control participants, TBI patients increased functional connectivity from prefrontal regions towards two different networks: 1) a subcortical network including part of the motor network, basal ganglia, cerebellum, hippocampus, amygdala, posterior cingulum and precuneus; and 2) a task-positive network, involving regions of the dorsal attention system together with the dorsolateral and ventrolateral prefrontal regions. We also found the increased prefrontal activation in TBI patients was correlated with some behavioural indices, such as the amount of body sway, whereby patients with worse balance activated frontal regions more strongly. The enhanced prefrontal activation found in TBI patients may provide the structural scaffold for stronger cognitive control of certain behavioural functions, consistent with the observation that various motor tasks are performed less automatically following TBI and that more cognitive control is associated with such actions.