Karla Michiels

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.

Topological correlations of structural and functional networks in patients with traumatic brain injury.

Despite an increasing amount of specific correlation studies between structural and functional connectivity, there is still a need for combined studies, especially in pathological conditions. Impairments of brain white matter (WM) and diffuse axonal injuries are commonly suspected to be responsible for the disconnection hypothesis in traumatic brain injury (TBI) patients. Moreover, our previous research on TBI patients shows a strong relationship between abnormalities in topological organization of brain networks and behavioral deficits. In this study, we combined task-related functional connectivity (using event-related fMRI) with structural connectivity (derived from fiber tractography using diffusion MRI data) estimates in the same participants (17 adults with TBI and 16 controls), allowing for direct comparison between graph metrics of the different imaging modalities. Connectivity matrices were computed covering the switching motor network, which includes the basal ganglia, anterior cingulate cortex/supplementary motor area, and anterior insula/inferior frontal gyrus. The edges constituting this network consisted of the partial correlations between the fMRI time series from each node of the switching motor network. The interregional anatomical connections between the switching-related areas were determined using the fiber tractography results. We found that graph metrics and hubs obtained showed no agreement in both groups. The topological properties of brain functional networks could not be solely accounted for by the properties of the underlying structural networks. However, combining complementary information from both imaging modalities could improve accuracy in prediction of switching performance. Direct comparison between functional task-related and anatomical structural connectivity, presented here for the first time in TBI patients, links two powerful approaches to map the patterns of brain connectivity that may underlie behavioral deficits in brain-injured patients.

Subcortical volume analysis in traumatic brain injury: the importance of the fronto-striato-thalamic circuit in task switching.

Traumatic brain injury (TBI) is associated with neuronal loss, diffuse axonal injury and executive dysfunction. Whereas executive dysfunction has traditionally been associated with prefrontal lesions, ample evidence suggests that those functions requiring behavioral flexibility critically depend on the interaction between frontal cortex, basal ganglia and thalamus. To test whether structural integrity of this fronto-striato-thalamic circuit can account for executive impairments in TBI we automatically segmented the thalamus, putamen and caudate of 25 patients and 21 healthy controls and obtained diffusion weighted images. We assessed components of executive function using the local-global task, which requires inhibition, updating and switching between actions. Shape analysis revealed localized atrophy of the limbic, executive and rostral-motor zones of the basal ganglia, whereas atrophy of the thalami was more global in TBI. This subcortical atrophy was related to white matter microstructural organization in TBI, suggesting that axonal injuries possibly contribute to subcortical volume loss. Global volume of the nuclei showed no clear relationship with task performance. However, the shape analysis revealed that participants with smaller volume of those subregions that have connections with the prefrontal cortex and rostral motor areas showed higher switch costs and mixing costs, and made more errors while switching. These results support the idea that flexible cognitive control over action depends on interactions within the fronto-striato-thalamic circuit.

Disturbed cortico-subcortical interactions during motor task switching in traumatic brain injury.

The ability to suppress and flexibly adapt motor behavior is a fundamental mechanism of cognitive control, which is impaired in traumatic brain injury (TBI). Here, we used a combination of functional magnetic resonance imaging and diffusion weighted imaging tractography to study changes in brain function and structure associated with motor switching performance in TBI. Twenty‐three young adults with moderate‐severe TBI and twenty‐six healthy controls made spatially and temporally coupled bimanual circular movements. A visual cue signaled the right hand to switch or continue its circling direction. The time to initiate the switch (switch response time) was longer and more variable in the TBI group and TBI patients exhibited a higher incidence of complete contralateral (left hand) movement disruptions. Both groups activated the basal ganglia and a previously described network for task‐set implementation, including the supplementary motor complex and bilateral inferior frontal cortex (IFC). Relative to controls, patients had significantly increased activation in the presupplementary motor area (preSMA) and left IFC, and showed underactivation of the subthalamic nucleus (STN) region. This altered functional engagement was related to the white matter microstructural properties of the tracts connecting preSMA, IFC, and STN. Both functional activity in preSMA, IFC, and STN, and the integrity of the connections between them were associated with behavioral performance across patients and controls. We suggest that damage to these key pathways within the motor switching network because of TBI, shifts the patients toward the lower end of the existing structure‐function‐behavior spectrum. Hum Brain Mapp, 2013.

Task switching in traumatic brain injury relates to cortico-subcortical integrity

Suppressing and flexibly adapting actions are a critical part of our daily behavioral repertoire. Traumatic brain injury (TBI) patients show clear impairments in this type of action control; however, the underlying mechanisms are poorly understood. Here, we tested whether white matter integrity of cortico‐subcortical pathways could account for impairments in task switching, an important component of executive functioning. Twenty young adults with TBI and eighteen controls performed a switching task requiring attention to global versus local stimulus features. Diffusion weighted images were acquired and whole brain tract‐based spatial statistics (TBSS) were used to explore where white matter damage was associated with switching impairment. A crossing fiber model and probabilistic tractography further identified the specific fiber populations. Relative to controls, patients with a history of TBI had a higher switch cost and were less accurate. The TBI group showed a widespread decline in fractional anisotropy (FA) throughout the TBSS skeleton. FA in the superior corona radiata showed a negative relationship with switch cost. More specifically, this involved cortico‐subcortical loops with the (pre‐)supplementary motor area and superior frontal gyrus. These findings provide evidence for damage to frontal‐subcortical projections in TBI, which is associated with task switching impairments. Hum Brain Mapp 35:2459–2469, 2014.

The relationship of visual extinction to luminance-contrast imbalances between left and right hemifield stimuli

Visual extinction was investigated in six right brain-damaged patients with left visual neglect, using a psychophysical paradigm. Orientation discrimination thresholds were determined for both left and right hemifield gratings presented either in isolation or simultaneously with a contralateral distractor grating. To minimize the influence of possible sensory-perceptual deficits, the luminances of both target and distractor gratings were chosen to be 20 times the luminances necessary to discriminate between horizontal and vertical grating orientations. When the visibility of target and distractor gratings was subjectively equalized in this way, neglect patients still showed a significant extinction effect, i.e. a significant interference of the right hemifield distractor with left hemifield orientation sensitivity. By manipulating the luminances of left and right hemifield gratings during bilateral simultaneous stimulus presentation, we demonstrated the role of luminance-contrast imbalances in eliciting visual extinction. Both decreasing the right distractor luminance and increasing the left target stimulus luminance resulted in an elimination of the observed extinction effects. These results show that not the absolute salience of one of two simultaneously presented stimuli, but the relative salience of both stimuli, is the crucial factor for inducing extinction.

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.

Proactive Response Inhibition and Subcortical Gray Matter Integrity in Traumatic Brain Injury

Background. Traumatic brain injury (TBI) has been associated with impairments in inhibiting prepotent motor responses triggered by infrequent external signals (ie, reactive inhibition). It is unclear whether proactive preparation to inhibit upcoming responses is also affected (ie, proactive inhibition). Successful inhibition relies on frontosubcortical interactions; therefore, impairments might be linked with gray matter atrophy in subcortical structures. Objective. We investigated reactive and proactive inhibition in TBI and control groups, and their relationship with subcortical gray matter. Methods. Participants performed a response inhibition task in which the probability of stopping was manipulated. Reactive inhibition was measured as the stop-signal reaction time (SSRT) when the probability of stopping was low. Proactive inhibition was measured as the change in SSRT and in go response time with increasing probability of stopping. Subcortical gray matter structures were automatically segmented with FSL-FIRST. Group differences in subregional volume and associations with reactive and proactive inhibition efficiency were investigated using shape analysis. Results. Reactive inhibition was impaired in TBI, as indicated by longer SSRTs. Moreover, the degree of atrophy in subregions of subcortical structures was predictive for SSRT in TBI. In contrast, proactive inhibition was not affected because both groups showed no response time slowing as a function of stopping probability. Proactive inhibition efficiency could be predicted by local volume in the anterior left putamen, bilateral pallidum, and right thalamus in controls but not in TBI. Conclusions. Our results reveal that proactive inhibition seems unaffected in TBI and that volume of subregions of subcortical nuclei is predictive for response inhibition proficiency and of clinical relevance in TBI.

Movement preparation and execution: differential functional activation patterns after traumatic brain injury

Years following the insult, patients with traumatic brain injury often experience persistent motor control problems, including bimanual coordination deficits. Previous studies revealed that such deficits are related to brain structural white and grey matter abnormalities. Here, we assessed, for the first time, cerebral functional activation patterns during bimanual movement preparation and performance in patients with traumatic brain injury, using functional magnetic resonance imaging. Eighteen patients with moderate-to-severe traumatic brain injury (10 females; aged 26.3 years, standard deviation = 5.2; age range: 18.4-34.6 years) and 26 healthy young adults (15 females; aged 23.6 years, standard deviation = 3.8; age range: 19.5-33 years) performed a complex bimanual tracking task, divided into a preparation (2 s) and execution (9 s) phase, and executed either in the presence or absence of augmented visual feedback. Performance on the bimanual tracking task, expressed as the average target error, was impaired for patients as compared to controls (P < 0.001) and for trials in the absence as compared to the presence of augmented visual feedback (P < 0.001). At the cerebral level, movement preparation was characterized by reduced neural activation in the patient group relative to the control group in frontal (bilateral superior frontal gyrus, right dorsolateral prefrontal cortex), parietal (left inferior parietal lobe) and occipital (right striate and extrastriate visual cortex) areas (Ps < 0.05). During the execution phase, however, the opposite pattern emerged, i.e. traumatic brain injury patients showed enhanced activations compared with controls in frontal (left dorsolateral prefrontal cortex, left lateral anterior prefrontal cortex, and left orbitofrontal cortex), parietal (bilateral inferior parietal lobe, bilateral superior parietal lobe, right precuneus, right primary somatosensory cortex), occipital (right striate and extrastriate visual cortices), and subcortical (left cerebellum crus II) areas (Ps < 0.05). Moreover, a significant interaction effect between Feedback Condition and Group in the primary motor area (bilaterally) (P < 0.001), the cerebellum (left) (P < 0.001) and caudate (left) (P < 0.05), revealed that controls showed less overlap of activation patterns accompanying the two feedback conditions than patients with traumatic brain injury (i.e. decreased neural differentiation). In sum, our findings point towards poorer predictive control in traumatic brain injury patients in comparison to controls. Moreover, irrespective of the feedback condition, overactivations were observed in traumatically brain injured patients during movement execution, pointing to more controlled processing of motor task performance.

Whiplash Injury and Mild Traumatic Brain Injury: Differential Effects onCognitive Functioning?

With regard to whiplash injury (WI) patients, some studies documented mild attention problems and a reduced speed of information processing. Most patients showed problems with sustained and/or divided attention. However, some patients had also problems with focused and alternating attention. Regarding memory, some studies detected mild (auditory-verbal and/or visuospatial) memory difficulties. Visuospatial and executive functions appeared mostly preserved. In mild traumatic brain injury (MTBI) patients, mild impairments in speed of information processing, (sustained, divided, focused and/or alternating) attention and (auditory-verbal and/or visuospatial) memory have been found. Furthermore, mild deficits could also be seen on tests measuring executive functions whereas visuospatial functioning seemed to be preserved. Until today, only two studies were devoted to evaluate possible differences in cognitive functioning between WI and MTBI patients. In these studies, both patient groups did not differ significantly with regard to measurements of attention, memory, and visuospatial and executive functions. Therefore, these authors conclude that MTBI patients do not perform more poorly on cognitive tests than WI patients, as might be expected from severity of trauma.