Stefan Sunaert

Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury

Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional 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.

Correlations Between White Matter Integrity and Motor Function in Traumatic Brain Injury Patients

Background. Deterioration of motor function is one of several clinical manifestations following traumatic brain injury (TBI) in children and adolescents. Objective. To investigate the relationship between white matter (WM) integrity using diffusion tensor imaging (DTI) and motor functioning in young TBI patients. Methods. A group with moderate to severe TBI (n = 24) and a control group (n = 17) were scanned using DTI along with standard anatomical scans. Using ExploreDTI software, WM regions/tracts that carry efferent output (motor) from the brain were evaluated, as well as the corpus callosum, brainstem, internal capsule, and subcortical WM structures. Motor function was assessed using the Movement Assessment Battery for Children (M-ABC), consisting of manual dexterity, ball skills, and static and dynamic balance items. Results. TBI patients were less successful on the M-ABC than the controls and showed lower WM fractional anisotropy (FA) in the corpus callosum, anterior corona radiata, corticospinal tract, and cerebellum. Decreased FA was associated with lower motor performance in the TBI group but not in the control group. Conclusion. This study provides evidence for a structural alteration of motor pathways and regions in children and adolescents with TBI that are correlated with motor functioning. Further studies may be able to identify therapeutic targets and monitor the effects of new interventions.

Brain activation to cues predicting inescapable delay in adolescent Attention Deficit/Hyperactivity Disorder: an fMRI pilot study

BACKGROUNDnThe choice of small immediate over large delayed rewards (i.e., impulsive choice) is a signal marker of motivational style in Attention Deficit/Hyperactivity Disorder (ADHD). The delay aversion model proposes that, in part, this is a conditioned delay avoidance response. Here we test the prediction derived from this model that, in ADHD, cues predicting inescapable delay differentially activate brain regions shown previously to be responsive to motivationally salient, negatively valenced environmental events.nnnMETHODSnTen adolescents with ADHD and 10 age matched controls performed a simple speeded reaction time task under two conditions. On Escape Delay trials slow responses only were punished by the imposition of post-response delay periods. On No Escape Delay trials post-response delay occurred on all trials irrespective of response speed. Using functional Magnetic Resonance Imaging (fMRI) BOLD responses were acquired to compare anticipatory brain activation following the two cue types. ROI analyses found significant ADHD-related hyperactivation following No Escape compared to Escape Delay trial cues in the insula, amygdala, ventral striatum and orbito-frontal cortex.nnnCONCLUSIONnThe results of this pilot study provide further evidence for the role of altered motivational systems in ADHD and the most direct evidence for a biological basis of delay aversion.

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.

Bimanual Motor Coordination in Older Adults Is Associated with Increased Functional Brain Connectivity – A Graph-Theoretical Analysis

In bimanual coordination, older and younger adults activate a common cerebral network but the elderly also have additional activation in a secondary network of brain areas to master task performance. It remains unclear whether the functional connectivity within these primary and secondary motor networks differs between the old and the young and whether task difficulty modulates connectivity. We applied graph-theoretical network analysis (GTNA) to task-driven fMRI data in 16 elderly and 16 young participants using a bimanual coordination task including in-phase and anti-phase flexion/extension wrist movements. Network nodes for the GTNA comprised task-relevant brain areas as defined by fMRI activation foci. The elderly matched the motor performance of the young but showed an increased functional connectivity in both networks across a wide range of connectivity metrics, i.e., higher mean connectivity degree, connection strength, network density and efficiency, together with shorter mean communication path length between the network nodes and also a lower betweenness centrality. More difficult movements showed an increased connectivity in both groups. The network connectivity of both groups had “small world” character. The present findings indicate (a) that bimanual coordination in the aging brain is associated with a higher functional connectivity even between areas also activated in young adults, independently from task difficulty, and (b) that adequate motor coordination in the context of task-driven bimanual control in older adults may not be solely due to additional neural recruitment but also to aging-related changes of functional relationships between brain regions.

Microstructural Integrity of the Superior Cerebellar Peduncle Is Associated with an Impaired Proprioceptive Weighting Capacity in Individuals with Non-Specific Low Back Pain

Introduction Postural control is a complex sensorimotor task that requires an intact network of white matter connections. The ability to weight proprioceptive signals is crucial for postural control. However, research into central processing of proprioceptive signals for postural control is lacking. This is specifically of interest in individuals with non-specific low back pain (NSLBP), because impairments in postural control have been observed as possible underlying mechanisms of NSLBP. Therefore, the objective was to investigate potential differences in sensorimotor white matter microstructure between individuals with NSLBP and healthy controls, and to determine whether the alterations in individuals with NSLBP are associated with the capacity to weight proprioceptive signals for postural control. Methods The contribution of proprioceptive signals from the ankle and back muscles to postural control was evaluated by local muscle vibration in 18 individuals with NSLBP and 18 healthy controls. Center of pressure displacement in response to muscle vibration was determined during upright standing on a stable and unstable support surface. Diffusion magnetic resonance imaging was applied to examine whether this proprioceptive contribution was associated with sensorimotor white matter microstructure. Results Individuals with NSLBP showed a trend towards a reduced fractional anisotropy along the left superior cerebellar peduncle compared to healthy controls (pu200a=u200a0.039). The impaired microstructural integrity of the superior cerebellar peduncle in individuals with NSLBP was significantly correlated with the response to ankle muscle vibration (p<0.003). Conclusions In individuals with NSLBP, a decreased integrity of the superior cerebellar peduncle was associated with an increased reliance on ankle muscle proprioception, even on unstable support surface, which implies an impaired proprioceptive weighting capacity. Our findings emphasize the importance of the superior cerebellar peduncle in proprioceptive weighting for postural control in individuals with NSLBP.

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.