Differences in white matter structure and cortical thickness between patients with traumatic and idiopathic chronic neck pain: Associations with cognition and pain modulation?

Brain alterations are hypothesized to be present in patients with chronic whiplash-associated disorders (CWAD). The aim of this case-control study was to examine alterations in cortical thickness and white matter (WM) structure, and the presence of brain microhemorrhages in a patient group encountering chronic neck pain of traumatic origin (i.e., CWAD) when compared with a patient group characterized by nontraumatic chronic neck pain [i.e., chronic idiopathic neck pain (CINP)], and healthy controls. Furthermore, we aimed to investigate associations between brain structure on one hand and cognitive performance and central sensitization (CS) on the other hand. T1-weighted, diffusion-weighted and T2*-weighted magnetic resonance images of the brain were acquired in 105 women (31 controls, 37 CINP, 37 CWAD) to investigate regional cortical thickness, WM structure, and microhemorrhages, respectively. Next, cognitive performance, and CS encompassing distant hyperalgesia and conditioned pain modulation (CPM) efficacy were examined. Cortical thinning in the left precuneus was revealed in CWAD compared with CINP patients. Also, decreased fractional anisotropy, together with increased values of mean diffusivity and radial diffusivity could be observed in the left cingulum hippocampus and tapetum in CWAD compared with CINP, and in the left tapetum in CWAD patients compared with controls. Moreover, the extent of WM structural deficits in the left tapetum coincided with decreased CPM efficacy in the CWAD group. This yields evidence for associations between decreased endogenous pain inhibition, and the degree of regional WM deficits in CWAD. Our results emphasize the role of structural brain alterations in women with CWAD compared with CINP.

Differential activation of brain areas in children with developmental coordination disorder during tasks of manual dexterity: An ALE meta-analysis.

Recent neuroimaging studies have reported atypical neural activation in children with Developmental Coordination Disorder (DCD) during tasks assessing manual dexterity. However, small sample sizes and subtle differences in task parameters have led to inconsistent findings, rendering interpretation difficult. The aim of the present meta-analysis was to quantitatively summarize this body of evidence using activation likelihood estimation (ALE) analysis to identify reliable regions of differential neural activation in children with DCD, compared to age-matched controls. Seven studies that adopted fMRI to compare children with and without DCD during manual performance were identified following a literature search. All were included in the ALE analysis. Compared to controls, children with DCD showed reduced activation during a manual dexterity task in the middle frontal gyrus, superior frontal gyrus, cerebellum, supramarginal gyrus, and inferior parietal lobule. Children with DCD showed greater activation in parts of the thalamus. Findings provide much needed clarification into the possible neural contributors to atypical manual dexterity in DCD and highlight the need for neuroimaging studies to include manual performance outcomes.

Associations between Measures of Structural Morphometry and Sensorimotor Performance in Individuals with Nonspecific Low Back Pain.

BACKGROUND AND PURPOSE: To date, most structural brain imaging studies in individuals with nonspecific low back pain have evaluated volumetric changes. These alterations are particularly found in sensorimotor-related areas. Although it is suggested that specific measures, such as cortical surface area and cortical thickness, reflect different underlying neural architectures, the literature regarding these different measures in individuals with nonspecific low back pain is limited. Therefore, the current study was designed to investigate the association between the performance on a sensorimotor task, more specifically the sit-to-stand-to-sit task, and cortical surface area and cortical thickness in individuals with nonspecific low back pain and healthy controls. MATERIALS AND METHODS: Seventeen individuals with nonspecific low back pain and 17 healthy controls were instructed to perform 5 consecutive sit-to-stand-to-sit movements as fast as possible. In addition, T1-weighted anatomic scans of the brain were acquired and analyzed with FreeSurfer. RESULTS: Compared with healthy controls, individuals with nonspecific low back pain needed significantly more time to perform 5 sit-to-stand-to-sit movements (P < .05). Brain morphometric analyses revealed that cortical thickness of the ventrolateral prefrontal cortical regions was increased in patients with nonspecific low back pain compared with controls. Furthermore, decreased cortical thickness of the rostral anterior cingulate cortex was associated with lower sit-to-stand-to-sit performance on an unstable support surface in individuals with nonspecific low back pain and healthy controls (r = -0.47, P < .007). In addition, a positive correlation was found between perceived pain intensity and cortical thickness of the superior frontal gyrus (r = 0.70, P < .002) and the pars opercularis of the inferior ventrolateral prefrontal cortex (r = 0.67, P < .004). Hence, increased cortical thickness was associated with increased levels of pain intensity in individuals with nonspecific low back pain. No associations were found between cortical surface area and the pain characteristics in this group. CONCLUSIONS: The current study suggests that cortical thickness may contribute to different aspects of sit-to-stand-to-sit performance and perceived pain intensity in individuals with nonspecific low back pain.

Revealing hot executive function in children with motor coordination problems: What's the go?

Recent research suggests that children with Developmental Coordination Disorder (DCD) often show deficits in executive functioning (EF) and, more specifically, the ability to use inhibitory control in 'hot', emotionally rewarding contexts. This study optimized the assessment of sensitivity of children with DCD to emotionally significant stimuli by using easily discriminable emotional expressions in a go/no-go task. Thirty-six children (12 with DCD), aged 7-12years, completed an emotional go/no-go task in which neutral facial expressions were paired with either happy or sad ones. Each expression was used as both, a go and no-go target in different runs of the task. There were no group differences in omission errors; however, the DCD group made significantly more commission errors to happy no-go faces. The particular pattern of performance in DCD confirms earlier reports of (hot) EF deficits. Specifically, a problem of inhibitory control appears to underlie the atypical pattern of performance seen in DCD on both cold and hot EF tasks. Disrupted coupling between cognitive control and emotion processing networks, such as fronto-parietal and fronto-striatal networks, may contribute to reduced inhibitory control in DCD. The implications for a broader theoretical account of DCD are discussed, as are implications for intervention.

Overcoming the effects of false positives and threshold bias in graph theoretical analyses of neuroimaging data.

Graph theory (GT) is a powerful framework for quantifying topological features of neuroimaging-derived functional and structural networks. However, false positive (FP) connections arise frequently and influence the inferred topology of networks. Thresholding is often used to overcome this problem, but an appropriate threshold often relies on a priori assumptions, which will alter inferred network topologies. Four common network metrics (global efficiency, mean clustering coefficient, mean betweenness and smallworldness) were tested using a model tractography dataset. It was found that all four network metrics were significantly affected even by just one FP. Results also show that thresholding effectively dampens the impact of FPs, but at the expense of adding significant bias to network metrics. In a larger number (n=248) of tractography datasets, statistics were computed across random group permutations for a range of thresholds, revealing that statistics for network metrics varied significantly more than for non-network metrics (i.e., number of streamlines and number of edges). Varying degrees of network atrophy were introduced artificially to half the datasets, to test sensitivity to genuine group differences. For some network metrics, this atrophy was detected as significant (p<0.05, determined using permutation testing) only across a limited range of thresholds. We propose a multi-threshold permutation correction (MTPC) method, based on the cluster-enhanced permutation correction approach, to identify sustained significant effects across clusters of thresholds. This approach minimises requirements to determine a single threshold a priori. We demonstrate improved sensitivity of MTPC-corrected metrics to genuine group effects compared to an existing approach and demonstrate the use of MTPC on a previously published network analysis of tractography data derived from a clinical population. In conclusion, we show that there are large biases and instability induced by thresholding, making statistical comparisons of network metrics difficult. However, by testing for effects across multiple thresholds using MTPC, true group differences can be robustly identified.

Hyperconnectivity in juvenile myoclonic epilepsy: a network analysis.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is a common idiopathic (genetic) generalized epilepsy (IGE) syndrome characterized by impairments in executive and cognitive control, affecting independent living and psychosocial functioning. There is a growing consensus that JME is associated with abnormal function of diffuse brain networks, typically affecting frontal and fronto-thalamic areas. METHODS: Using diffusion MRI and a graph theoretical analysis, we examined bivariate (network-based statistic) and multivariate (global and local) properties of structural brain networks in patients with JME (N = 34) and matched controls. Neuropsychological assessment was performed in a subgroup of 14 patients. RESULTS: Neuropsychometry revealed impaired visual memory and naming in JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and controls exhibited a small world topology in their white matter networks, with no significant differences in the global multivariate network properties between the groups. The network-based statistic approach identified one subnetwork of hyperconnectivity in the JME group, involving primary motor, parietal and subcortical regions. Finally, there was a significant positive correlation in structural connectivity with cognitive task performance. CONCLUSIONS: Our findings suggest that structural changes in JME patients are distributed at a network level, beyond the frontal lobes. The identified subnetwork includes key structures in spike wave generation, along with primary motor areas, which may contribute to myoclonic jerks. We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients.

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.

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.

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 (r s 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 (r s 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.

Motor learning-induced changes in functional brain connectivity as revealed by means of graph-theoretical network analysis.

Complex bimanual motor learning causes specific changes in activation across brain regions. However, there is little information on how motor learning changes the functional connectivity between these regions, and whether this is influenced by different sensory feedback modalities. We applied graph-theoretical network analysis (GTNA) to examine functional networks based on motor-task-related fMRI activations. Two groups learned a complex 90° out-of-phase bimanual coordination pattern, receiving either visual or auditory feedback. 3T fMRI scanning occurred before (day 0) and after (day 5) training. In both groups, improved motor performance coincided with increased functional network connectivity (increased clustering coefficients, higher number of network connections and increased connection strength, and shorter communication distances). Day×feedback interactions were absent but, when examining network metrics across all examined brain regions, the visual group had a marginally better connectivity, higher connection strength, and more direct communication pathways. Removal of feedback had no acute effect on the functional connectivity of the trained networks. Hub analyses showed an importance of specific brain regions not apparent in the standard fMRI analyses. These findings indicate that GTNA can make unique contributions to the examination of functional brain connectivity in motor learning.

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.

Keeping an eye on imagery: the role of eye movements during motor imagery training.

We recently found that spontaneous eye movements occur during motor imagery of hand movements, which are similar to those made during physical execution. In physical execution, eye movements have been shown to play an important role during training. In motor imagery practice, however, their effect remains unclear. Therefore, in the present study, we examined the role of eye movements during motor imagery practice with specific interest in the impact of task complexity and effector specificity. Thirty-six young healthy participants were tested before and after 4 days of visual motor imagery training on a Virtual Radial Fitts' task with different indices of difficulty. Training was performed with the nondominant hand only. Subjects were divided into a group that trained while spontaneous eye movements were allowed, one that kept the eyes fixed during training, and a control group. Electro-oculography and electromyography signals were monitored to guarantee task compliance during imagery. The results indicated that eye movements during imagery did not affect the temporal parameters of the trained movement. They did, however, help to achieve maximal gains in movement accuracy and efficiency. These positive effects on the spatial parameters were most pronounced during conditions with high accuracy demands and were present for both the trained and the untrained hand. These findings contribute to guidelines for optimizing training protocols based on motor imagery.

Brain-behavior relationships in young traumatic brain injury patients: fractional anisotropy measures are highly correlated with dynamic visuomotor tracking performance.

Traumatic brain injury (TBI) patients have a high incidence of eye-hand coordination deficits. Diffuse axonal injury is common in TBI and is presumed to contribute to persistent motor problems. Using Diffusion Tensor Imaging (DTI), this study sought to identify changes in (sensori)motor white matter (WM) pathways/regions in a TBI group during the chronic recovery stage. A secondary objective was to examine the relationship between WM integrity and upper-limb visuomotor tracking performance. A young TBI (n=17) and control (n=14) group performed a dynamic tracking task, characterized by increasing information processing speed and predictive movement control. DTI scans were administered along with standard anatomical scans. The TBI group was found to perform inferior to the control group on the tracking task. Decreased fractional anisotropy was found in the TBI group in dedicated pathways involved in transmission of afferent and efferent information, i.e., corticospinal tract, posterior thalamic radiation, and optic radiation, due to increased diffusivity parallel and perpendicular to axonal fibre direction. This decrease in WM integrity was associated with inferior visuomotor tracking performance. Moreover, discriminant function analysis demonstrated that the model, based on the combined application of DTI and behavioral measures, was the most effective in distinguishing between TBI patients and controls. This study shows that specific eye-hand coordination deficits in a young TBI group are related to microstructural abnormalities in task-specific cerebral WM structures. Measures of white matter integrity are potentially important biomarkers for TBI that may support prognosis of motor deficits.

Neural correlates of motor dysfunction in children with traumatic brain injury: exploration of compensatory recruitment patterns.

Traumatic brain injury (TBI) is a common form of disability in children. Persistent deficits in motor control have been documented following TBI but there has been less emphasis on changes in functional cerebral activity. In the present study, children with moderate to severe TBI (n = 9) and controls (n = 17) were scanned while performing cyclical movements with their dominant and non-dominant hand and foot according to the easy isodirectional (same direction) and more difficult non-isodirectional (opposite direction) mode. Even though the children with TBI were shown to be less successful on various items of a clinical motor test battery than the control group, performance on the coordination task during scanning was similar between groups, allowing a meaningful interpretation of their brain activation differences. fMRI analysis revealed that the TBI children showed enhanced activity in medial and anterior parietal areas as well as posterior cerebellum as compared with the control group. Brain activation generally increased during the non-isodirectional as compared with the isodirectional mode and additional regions were involved, consistent with their differential degree of difficulty. However, this effect did not interact with group. Overall, the findings indicate that motor impairment in TBI children is associated with changes in functional cerebral activity, i.e. they exhibit compensatory activation reflecting increased recruitment of neural resources for attentional deployment and somatosensory processing.

Deficits in executed and imagined aiming performance in brain-injured children.

Motor disorders are a frequent consequence of acquired brain injury (ABI) in children and much effort is currently invested in alleviating these deficits. The aim of the present study was to test motor imagery (MI) capabilities in children with ABI (n=25) and an age- and gender-matched control group (n=25). A computerized Virtual Radial Fitts Task (VRFT) was used to investigate the speed-accuracy trade-offs (or Fitts' law) that occur as target size is varied for both executed and imagined performance. In the control group, the speed for accuracy trade-off for both executed and imagined performance conformed to Fitts' law. In the ABI group, only executed movements conformed to Fitts' law. These findings suggest that children with ABI show an inferior ability to imagine the time needed to complete goal-directed movements with differential difficulty levels.