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.

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.

Cortical regions involved in the observation of bimanual actions.

Although we are beginning to understand how observed actions performed by conspecifics with a single hand are processed and how bimanual actions are controlled by the motor system, we know very little about the processing of observed bimanual actions. We used fMRI to compare the observation of bimanual manipulative actions with their unimanual components, relative to visual control conditions equalized for visual motion. Bimanual action observation did not activate any region specialized for processing visual signals related to this more elaborated action. On the contrary, observation of bimanual and unimanual actions activated similar occipito-temporal, parietal and premotor networks. However, whole-brain as well as region of interest (ROI) analyses revealed that this network functions differently under bimanual and unimanual conditions. Indeed, in bimanual conditions, activity in the network was overall more bilateral, especially in parietal cortex. In addition, ROI analyses indicated bilateral parietal activation patterns across hand conditions distinctly different from those at other levels of the action-observation network. These activation patterns suggest that while occipito-temporal and premotor levels are involved with processing the kinematics of the observed actions, the parietal cortex is more involved in the processing of static, postural aspects of the observed action. This study adds bimanual cooperation to the growing list of distinctions between parietal and premotor cortex regarding factors affecting visual processing of observed actions.

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.

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.

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.

Impaired eye movements in post-concussion syndrome indicate suboptimal brain function beyond the influence of depression, malingering or intellectual ability.

Post-concussion syndrome (PCS) can affect up to 20%-30% of patients with mild closed head injury (mCHI), comprising incomplete recovery and debilitating persistence of post-concussional symptoms. Eye movements relate closely to the functional integrity of the injured brain and eye movement function is impaired post-acutely in mCHI. Here, we examined whether PCS patients continue to show disparities in eye movement function at 3-5 months following mCHI compared with patients with good recovery. We hypothesized that eye movements might provide sensitive and objective functional markers of ongoing cerebral impairment in PCS. We compared 36 PCS participants (adapted World Health Organization guidelines) and 36 individually matched controls (i.e. mCHI patients of similar injury severity but good recovery) on reflexive, anti- and self-paced saccades, memory-guided sequences and smooth pursuit. All completed neuropsychological testing and health status questionnaires. Mean time post-injury was 140 days in the PCS group and 163 days in the control group. The PCS group performed worse on anti-saccades, self-paced saccades, memory-guided sequences and smooth pursuit, suggesting problems in response inhibition, short-term spatial memory, motor-sequence programming, visuospatial processing and visual attention. This poorer oculomotor performance included several measures beyond conscious control, indicating that subcortical functionality in the PCS group was poorer than expected after mCHI. The PCS group had poorer neuropsychological function (memory, complex attention and executive function). Analysis of covariance showed oculomotor differences to be practically unaffected by group disparities in depression and estimated intellectual ability. Compared with neuropsychological tests, eye movements were more likely to be markedly impaired in PCS cases with high symptom load. Poorer eye movement function, and particularly poorer subcortical oculomotor function, correlated more with post-concussive symptom load and problems on activities of daily living whilst poorer neuropsychological function exhibited slightly better correlations with measures of mental health. Our findings that eye movement function in PCS does not follow the normal recovery path of eye movements after mCHI are indicative of ongoing cerebral impairment. Whilst oculomotor and neuropsychological tests partially overlapped in identifying impairment, eye movements showed additional dysfunction in motor/visuospatial areas, response inhibition, visual attention and subcortical function. Poorer subconscious oculomotor function in the PCS group supports the notion that PCS is not merely a psychological entity, but also has a biological substrate. Measurement of oculomotor function may be of value in PCS cases with a high symptom load but an otherwise unremarkable assessment profile. Routine oculomotor testing should be feasible in centres with existing access to this technology.

A new approach to predicting postconcussion syndrome after mild traumatic brain injury based upon eye movement function.

Following on from our earlier findings of a close relationship between motor function and outcome after mild traumatic brain injury (mTBI), this study examined whether it might be possible to predict poor recovery in the form of postconcussion syndrome (PCS) based upon early eye and arm motor function. Within 1 week post-injury, we assessed 37 mTBI patients on measures of saccades, oculomotor smooth pursuit, upper-limb visuomotor function, neuropsychological status, and self-reported health condition. At 3 months, 8 patients met the criteria for PCS. Using discriminant function analyses, we examined whether this future PCS-group could be identified prospectively based on motor function, neuropsychological status, and self-reported health condition at 1 week post-injury. Early eye movement function was the most effective in distinguishing between PCS and non-PCS patients, achieving a sensitivity and specificity of 100% in the present sample. This was followed by self-reported early health condition (sensitivity: 87%, specificity: 97%), early upper-limb motor performance (87%, 97%), neuropsychological function (62%, 100%), and age, gender, education and clinical measures of trauma severity (37%, 87%). Leave-one-out validation analyses confirmed eye movements as the most robust discriminator (sensitivity: 62%, specificity: 97%). Assessment of eye movement function after mTBI may contribute to a prospective identification of patients who develop PCS, supporting the targeting of early health-care intervention.

Recovery in the first year after mild head injury: divergence of symptom status and self-perceived quality of life.

OBJECTIVE: To examine self-perceived health status during the first year following mild closed head injury. METHODS: At 1 week, and at 3, 6 and 12 months post-injury, 37 patients with mild closed head injury completed written versions of the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ), the Rivermead Head-Injury Follow-up Questionnaire (RHIFQ) and the SF-36 Health Survey. Thirty-seven controls provided baselines for the SF-36 and the RPSQ. RESULTS: The 3 questionnaires conveyed differing impressions of recovery. On the RPSQ, the patients exhibited ongoing symptomatic complaints and higher scores compared with controls. The RHIFQ conveyed a better recovery in terms of everyday function. The SF-36 showed the best recovery, with the mild closed head injury group achieving normal scores at 3, 6 and 12 months. Regression analyses indicated an influence of IQ, but not of age, education, or clinical measures of injury severity, on long-term health status. CONCLUSION: Recovery after mild closed head injury can involve a dichotomy of persistent post-concussional symptoms but relatively normal functionality and quality of life. In addition to indicating an influence of IQ on perception of recovery in mild closed head injury, our findings demonstrate that the nature of self-report questionnaires considerably influences the picture of recovery. This emphasizes the importance of methods unaffected by IQ and self-evaluative accuracy in the assessment of mild closed head injury.

Mild head injury--a close relationship between motor function at 1 week post-injury and overall recovery at 3 and 6 months.

Based on previous findings of impaired eye and arm motor control after mild closed head injury (CHI), this study examined whether early eye and arm motor function, and the level of post-injury cerebral dysfunction manifested in motor control, relates systematically to recovery at 3 and 6 months after mild CHI. At 1 week post-injury, we assessed oculomotor function, upper-limb visuomotor performance, and cognitive status in 37 mild CHI patients. Re-examination at 3 and 6 months determined outcome in terms of postconcussional symptoms and performance of everyday tasks, as assessed by the Rivermead Postconcussion Symptoms Questionnaire, the Rivermead Head Injury Follow-up Questionnaire and the SF-36 Health Survey. We then examined the association of early motor function, cognitive status and self-reported health condition with outcome using linear regression. Motor-based regression models explained a high proportion of the variance in outcome (70-89%), with motor function at 1 week being more closely related to outcome at 3 and 6 months than early psychometric assessment (13-32%) or self-reported health status (54-79%). These motor-based models incorporated subcortical/subconscious motor functions alongside motor functions that are subject to volitional control and are primarily mediated by frontal, parietal and temporal cortical brain regions. Early assessment of eye and arm motor function may help in improving accuracy of outcome prediction after mild CHI. Such assessment may assist in the better targeting of early health care intervention and help decrease head-trauma-related morbidity and rehabilitation costs.

Motor deficits and recovery during the first year following mild closed head injury.

OBJECTIVE: This study examined motor impairments over 1 year following mild closed head injury (CHI). It is the first study to serially assess long-term oculomotor and upper-limb visuomotor function following mild head trauma. METHODS: Thirty-seven patients with mild CHI and 37 matched controls were compared at 1 week, 3 months and 6 months and 31 available pairs at 12 months post-injury on measures of saccades, oculomotor smooth pursuit, upper-limb visuomotor function and neuropsychological performance. Symptomatic recovery was sampled using the Rivermead Postconcussion Symptoms Questionnaire. RESULTS: At 1 week, the group with CHI reported high levels of post-concussional symptoms and exhibited prolonged saccade latencies, increased directional errors, decreased saccade accuracy and impaired fast sinusoidal smooth pursuit concomitant with increased arm movement reaction time, decreased arm movement speed and decreased motor accuracy on upper-limb visuomotor tracking tasks. Neuropsychological testing identified deficits only in verbal learning and speed of processing while attention, short-term/working memory and general cognitive performance were preserved. At 3 and 6 months, the group with CHI continued to show deficits on several oculomotor and upper-limb visuomotor measures in combination with some deficits on verbal learning and improved, yet abnormal, levels of post-concussional symptoms. At 12 months, the group with CHI had no cognitive impairment but residual deficits in eye and arm motor function and continued to show elevated levels of post-concussional symptoms. CONCLUSIONS: The findings indicate that multiple motor systems are measurably impaired up to 12 months following mild CHI and that instrumented motor assessment may provide sensitive and objective markers of cerebral dysfunction during recovery from mild head trauma independent of neuropsychological assessment and patient self-report.

Distribution of microstructural damage in the brains of professional boxers: a diffusion MRI study.

PURPOSE: To investigate and localize cerebral abnormalities in professional boxers with no history of moderate or severe head trauma. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was used to determine the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the brains of 81 professional male boxers and 12 male control subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values was performed using statistical parametric mapping (SPM). From this objective analysis, regions of microstructural abnormalities in the brains of the boxers were located. RESULTS: Increases in the ADC, and decreases in FA were identified in deep white matter (WM), while decreases in ADC were identified in cortical gray matter (GM). Regions of positive correlation between ADC and age were also found in both the boxer and control groups, although the regions and strength of the correlation were not the same in each group. CONCLUSION: Using VBA, we localized previously unreported abnormalities in the brains of professional boxers. These abnormalities are assumed to reflect cumulative (chronic) brain injury resulting from nonsevere head trauma.

The impact of mild closed head injury on involuntary saccadic adaptation: evidence for the preservation of implicit motor learning.

OBJECTIVE: Mild closed head injury (CHI) can impair performance on volitional saccades (fast eye movements), with poorer saccade accuracy being one of the principal deficits. Assessing a patient group with known deficits of volitional saccades, the authors investigated whether mild CHI similarly impairs the implicit adaptation of visually-guided (reflexive) saccades, an important process which maintains saccadic accuracy. METHODS: Within 2 weeks following mild CHI, 30 patients and 30 matched controls were compared on a computerized paradigm, which artificially induced saccadic adaptation. In response to an initial stimulus, subjects made a saccade during which the stimulus was displaced centripetally causing the initial (primary) saccade to be inaccurate. While these intra-saccadic changes remained unnoticed by the subjects, the displacements gradually caused adaptive saccadic hypometria. RESULTS: No differences in adaptation were found between the CHI group and the controls (F(1, 29) = 0.51, p = 0.48). This finding indicates that mild CHI does not impair implicit reflexive saccade adaptation and suggests that cerebellar function and functions of deeper brain structures such as the thalamus, superior colliculus and the basal ganglia may be largely preserved following mild CHI. The current results support the notion that the profile of oculomotor function after mild CHI reflects a centripetal gradient of impairment and relates closely to the functional integrity of the injured brain.

Eye movement and visuomotor arm movement deficits following mild closed head injury.

Based on increasing evidence that even mild closed head injury (CHI) can cause considerable neural damage throughout the brain, we hypothesized that mild CHI will disrupt the complex cerebral networks concerned with oculomotor and upper-limb visuomotor control, resulting in impaired motor function. Within 10 days following mild CHI (Glasgow Coma Scale 13-15, alteration of consciousness <20 min), we compared 30 patients (15-37 years) and 30 matched controls on different types of saccades, oculomotor smooth pursuit (sine and random), upper-limb visuomotor performance and several neuropsychological tests known to be sensitive to head trauma. Simple reflexive saccades were not impaired, whereas, on the antisaccade task, the CHI group demonstrated prolonged saccadic latencies, a marginally higher number of directional errors and poorer spatial accuracy. The CHI group exhibited more directional errors and impaired motor accuracy on memory-guided sequences of saccades and produced fewer self-paced saccades within 30 s. Most measures of sinusoidal and random oculomotor smooth pursuit showed no deficits, with the exception of a prolonged lag on random smooth pursuit in the CHI group. While arm movement reaction time and arm steadiness were not impaired, the CHI group showed decreased arm movement speed and decreased upper-limb motor accuracy. Conversely, after controlling for IQ, the CHI group had few head trauma-related neuropsychological deficits. These results indicate that multiple motor systems can be impaired following mild CHI and that this can occur independently of neuropsychological impairment. Our study also indicates that quantitative tests of oculomotor and upper-limb visuomotor function may provide sensitive markers of cerebral dysfunction, suggesting the potential use of such tests to supplement patient assessment. To our knowledge, this study is the first to demonstrate the presence of oculomotor or visuomotor deficits following mild CHI.