Laterality indices consensus initiative (LICI): A Delphi expert survey report on recommendations to record, assess, and report asymmetry in human behavioural and brain research.

Laterality indices (LIs) quantify the left-right asymmetry of brain and behavioural variables and provide a measure that is statistically convenient and seemingly easy to interpret. Substantial variability in how structural and functional asymmetries are recorded, calculated, and reported, however, suggest little agreement on the conditions required for its valid assessment. The present study aimed for consensus on general aspects in this context of laterality research, and more specifically within a particular method or technique (i.e., dichotic listening, visual half-field technique, performance asymmetries, preference bias reports, electrophysiological recording, functional MRI, structural MRI, and functional transcranial Doppler sonography). Experts in laterality research were invited to participate in an online Delphi survey to evaluate consensus and stimulate discussion. In Round 0, 106 experts generated 453 statements on what they considered good practice in their field of expertise. Statements were organised into a 295-statement survey that the experts then were asked, in Round 1, to independently assess for importance and support, which further reduced the survey to 241 statements that were presented again to the experts in Round 2. Based on the Round 2 input, we present a set of critically reviewed key recommendations to record, assess, and report laterality research for various methods.

Structural perisylvian asymmetry in naturally occurring atypical language dominance.

Functional and anatomical hemispheric asymmetries abound in the neural language system, yet the relationship between them remains elusive. One attractive proposal is that structural interhemispheric differences reflect or even drive functional language laterality. However, studies on structure-function couplings either find that left and right language dominant individuals display similar leftward structural asymmetry or yield inconsistent results. The current study aimed to replicate and extend prior work by comparing structural asymmetries between neurologically healthy left-handers with right hemispheric language dominance (N = 24) and typically lateralized left-handed controls (N = 39). Based on structural MRI data, anatomical measures of six 'language-related' perisylvian structures were derived, including the surface area of five gray matter regions with known language functions and the FDC (combined fiber density and fiber-bundle cross-sectional area) of the arcuate fasciculus. Only the surface area of the pars triangularis and the anterior insula differed significantly between participant groups, being on average leftward asymmetric in those with typical dominance, but right lateralized in volunteers with atypical language specialization. However, these findings did not survive multiple testing correction and the asymmetry of these structures demonstrated much inter-individual variability in either subgroup. By integrating our findings with those reported previously we conclude that while some perisylvian anatomical asymmetries may differ subtly between typical and atypical speech dominants at the group level, they serve as poor participant-specific predictors of hemispheric language specialization.

Graph Measure Based Connectivity in Chronic Pain Patients: A Systematic Review.

BACKGROUND: Chronic pain affects 20 to 30% of the adult population worldwide and is consequently the leading cause of disability. Current developments in brain imaging technology are increasing the understanding of the pathophysiology of (chronic) pain and enabling the possibility to objectify pain. As a result, our view of the brain has evolved from a static organ to a dynamic organ that constitutes an adaptable network of linked regions. Graph theory has emerged as a framework to analyze such networks and can be applied to investigate a range of topological properties of both the functional and structural brain network or connectome, thus providing meaningful information about the organization of human brain networks. OBJECTIVES: The aim of this systematic review is to determine whether connectivity differs between chronic pain patients and healthy controls by integrating previous studies that performed graph analyses on structural or functional connectivity. A secondary aim was to determine whether graph measures correlate to clinical outcomes. STUDY DESIGN: Systematic review. METHODS: Relevant articles were searched for in PubMed and Web of Science. These were screened against certain criteria and assessed for quality. RESULTS: On a global level the transitivity, betweenness centrality, intramodular degree, and rich club organization differed between chronic pain patients and healthy controls, but the path length, modularity, degree, and (Hub Disruption Index [HDI] of) participation coefficient did not differ between both groups, along with the small-worldness. Conflicting evidence still remains about a number of global graph measures, namely the global efficiency, local efficiency, clustering coefficient, and HDI of degree. Significant correlations were found between several nodal and global graph measures on one hand, and clinical outcomes related to pain, disability, and motor control on the other hand. LIMITATIONS: No clear conclusions could be made about the majority of the nodal measures, as they were often based on single studies. CONCLUSION: Differences between chronic pain patients and healthy controls were mostly observed for the global graph measures. Future research is still needed to validate the obtained findings and to expand this knowledge to the chronic pain populations that were not discussed in the included papers.

Fibre-specific laterality of white matter in left and right language dominant people.

Language is the most commonly described lateralised cognitive function, relying more on the left hemisphere compared to the right hemisphere in over 90% of the population. Most research examining the structure-function relationship of language lateralisation only included people showing a left language hemisphere dominance. In this work, we applied a state-of-the-art "fixel-based" analysis approach, allowing statistical analysis of white matter micro- and macrostructure on a fibre-specific level in a sample of participants with left and right language dominance (LLD and RLD). Both groups showed a similar extensive pattern of white matter lateralisation including a comparable leftwards lateralisation of the arcuate fasciculus, regardless of their functional language lateralisation. These results suggest that lateralisation of language functioning and the arcuate fasciculus are driven by independent biases. Finally, a significant group difference of lateralisation was detected in the forceps minor, with a leftwards lateralisation in LLD and rightwards lateralisation for the RLD group.

Associations between different white matter properties and reward-based performance modulation.

Humans can be motivated by the prospect of gaining a reward. However, the extent to which we are affected by reward information differs from person to person. A possible mechanism underlying these inter-individual differences may be alterations in white matter (WM) microstructure; however, the relationship between WM properties and reward-based behaviour in healthy participants has not yet been explored. Here, we used a fixel-based approach to investigate potential associations between WM tracts and performance in a reward-cuing task. We found that WM properties in the corpus callosum, right uncinate fasciculus, left ventral cingulum, and accumbofrontal tracts were inversely related to reward-triggered performance benefits (indexed by faster reaction times). Moreover, smaller WM property values in the corpus callosum, uncinate fasciculus, and accumbofrontal tracts were associated with higher scores on the Behavioral Inhibition System scale, reflecting greater sensitivity to potential punishment. Finally, we also observed associations between functional hemodynamic activity in the ventral striatum and WM microstructure. The finding that reward-based behavioural benefits are related to lower measures of WM tracts is in contrast to studies linking higher WM metrics to superior cognitive performance. We interpret the current pattern in terms of higher susceptibility to motivationally relevant stimuli, which is in line with the current and previous studies reporting inverse relationships between WM properties and motivational traits. Taking a broader perspective, such propensities may only be beneficial up to a certain point, at which these may become detrimental to performance and even manifest as impulsive and addictive behaviour.

Evaluating the performance of the visual half field paradigm as a screening tool to detect right hemispheric language dominance.

Language is among the most studied functional asymmetries, yet little is known about right hemispheric language dominance. Because of its low prevalence, including a big sample of individuals with this variant of brain organization implies testing large groups, which may not be feasible when using expensive techniques. One solution involves screening a large sample using a cost-efficient method and next inviting only those participants flagged as potentially right dominant for follow-up investigation. The behavioural visual half field paradigm has previously been validated and successfully applied in this manner. We report a large-scale visual half field screening performed in 315 left-handers to detect such individuals for subsequent MRI scanning. Of 38 cases selected as probably right language dominant based on a left visual half field advantage (>20 ms), 22 (58%) were confirmed by language fMRI to be rightward lateralized. This study also explored means to improve the predictive performance of the visual half field task. While we found its performance depended strongly on the chosen cut-off, overall, reaction time criteria resulted in higher true positive rates, while those based on accuracy led to superior positive predictive values. The most optimal strategy, however, may involve combining criteria considering both accuracy and reaction time.

Hemispheric dominance for visuospatial attention does not predict the direction of pseudoneglect.

Pseudoneglect refers to a tendency of neurologically healthy individuals to produce leftward perceptual biases during spatial tasks, which is traditionally measured using line bisection tasks. This behavioral asymmetry is often explained as a consequence of right hemispheric dominance for visuospatial attention. The present study directly tested this notion by comparing line bisection performance between left-handers with either right hemispheric dominance (RVSD, N = 40) or "atypical" left hemispheric dominance (LVSD, N = 23) for visuospatial attention as determined by fMRI. Although we expected a reversal of pseudoneglect in participants with LVSD, our results show that they equally often err to the left of the true center compared to RVSD controls (74% of LVSD participants and 80% of RVSD participants). However, the magnitude of misbisections was found to be slightly, but significantly, smaller in the LVSD subgroup.We conclude that hemispheric asymmetry for visuospatial attention is not the main determinant of pseudoneglect as is commonly thought, but rather only constitutes one of the multiple factors which (subtly) contributes to its direction and magnitude.

Mirrored brain organization: Statistical anomaly or reversal of hemispheric functional segregation bias?

Humans demonstrate a prototypical hemispheric functional segregation pattern, with language and praxis lateralizing to the left hemisphere and spatial attention, face recognition, and emotional prosody to the right hemisphere. In this study, we used fMRI to determine laterality for all five functions in each participant. Crucially, we recruited a sample of left-handers preselected for atypical (right) language dominance (n = 24), which allowed us to characterize hemispheric asymmetry of the other functions and compare their functional segregation pattern with that of left-handers showing typical language dominance (n = 39). Our results revealed that most participants with left language dominance display the prototypical pattern of functional hemispheric segregation (44%) or deviate from this pattern in only one function (35%). Similarly, the vast majority of right language dominant participants demonstrated a completely mirrored brain organization (50%) or a reversal for all but one cognitive function (32%). Participants deviating by more than one function from the standard segregation pattern showed poorer cognitive performance, in line with an oft-presumed biological advantage of hemispheric functional segregation.

Network diffusion modeling predicts neurodegeneration in traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) is a heterogeneous disease with multiple neurological deficits that evolve over time. It is also associated with an increased incidence of neurodegenerative diseases. Accordingly, clinicians need better tools to predict a patient's long-term prognosis. METHODS: Diffusion-weighted and anatomical MRI data were collected from 17 adolescents (mean age = 15y8mo) with moderate-to-severe TBI and 19 healthy controls. Using a network diffusion model (NDM), we examined the effect of progressive deafferentation and gray matter thinning in young TBI patients. Moreover, using a novel automated inference method, we identified several injury epicenters in order to determine the neural degenerative patterns in each TBI patient. RESULTS: We were able to identify the subject-specific patterns of degeneration in each patient. In particular, the hippocampus, temporal cortices, and striatum were frequently found to be the epicenters of degeneration across the TBI patients. Orthogonal transformation of the predicted degeneration, using principal component analysis, identified distinct spatial components in the temporal-hippocampal network and the cortico-striatal network, confirming the vulnerability of these networks to injury. The NDM model, best predictive of the degeneration, was significantly correlated with time since injury, indicating that NDM can potentially capture the pathological progression in the chronic phase of TBI. INTERPRETATION: These findings suggest that network spread may help explain patterns of distant gray matter thinning, which would be consistent with Wallerian degeneration of the white matter connections (i.e., "diaschisis") from diffuse axonal injuries and multifocal contusive injuries, and the neurodegenerative patterns of abnormal protein aggregation and transmission, which are hallmarks of brain changes in TBI. NDM approaches could provide highly subject-specific biomarkers relevant for disease monitoring and personalized therapies in TBI.

Cognitive Training in Young Patients With Traumatic Brain Injury: A Fixel-Based Analysis.

Background. Traumatic brain injury (TBI) is associated with altered white matter organization and impaired cognitive functioning. Objective. We aimed to investigate changes in white matter and cognitive functioning following computerized cognitive training. Methods. Sixteen adolescents with moderate-to-severe TBI (age 15.6 ± 1.8 years, 1.2-4.6 years postinjury) completed the 8-week BrainGames program and diffusion weighted imaging (DWI) and cognitive assessment at time point 1 (before training) and time point 2 (after training). Sixteen healthy controls (HC) (age 15.6 ± 1.8 years) completed DWI assessment at time point 1 and cognitive assessment at time point 1 and 2. Fixel-based analyses were used to examine fractional anisotropy (FA), mean diffusivity (MD), and fiber cross-section (FC) on a whole brain level and in tracts of interest. Results. Patients with TBI showed cognitive impairments and extensive areas with decreased FA and increased MD together with an increase in FC in the body of the corpus callosum and left superior longitudinal fasciculus (SLF) at time point 1. Patients improved significantly on the inhibition measure at time point 2, whereas the HC group remained unchanged. No training-induced changes were observed on the group level in diffusion metrics. Exploratory correlations were found between improvements on verbal working memory and reduced MD of the left SLF and between increased performance on an information processing speed task and increased FA of the right precentral gyrus. Conclusions. Results are indicative of positive effects of BrainGames on cognitive functioning and provide preliminary evidence for neuroplasticity associated with cognitive improvements following cognitive intervention in TBI.

White matter asymmetries in human situs inversus totalis.

Diffusion weighted imaging (DWI) was used to investigate white matter asymmetries in participants with situs inversus totalis (SIT) and matched controls. Regardless of visceral condition, hemispheric differences were found for the arcuate fasciculus (ARC) and the superior longitudinal fasciculus (SLF), which are involved in language and visuospatial functioning, respectively. The ARC appears lateralized to the left hemisphere, analogous to the left lateralization of functional areas associated with language. The SLF, on the other hand, is lateralized to the right, corresponding with rightward lateralization of visuospatial functioning. Interestingly, SIT participants show a significantly lower number of streamlines in the Uncinate Fasciculus (UNC). In addition, UNC volume appears associated with measures of cognitive performance, a finding in line with previously reported performance differences between SIT participants and controls.

Is diffuse axonal injury on susceptibility weighted imaging a biomarker for executive functioning in adolescents with traumatic brain injury?

Traumatic brain injury (TBI) is a heterogeneous disorder in which diffuse axonal injury (DAI) is an important component contributing to executive dysfunction. During adolescence, developing brain networks are especially vulnerable to acceleration-deceleration forces. We aimed to examine the correlation between DAI (number and localization) and executive functioning in adolescents with TBI. We recruited 18 adolescents with a mean age of 15y8m (SD = 1y7m), averaging 2.5 years after sustaining a moderate-to-severe TBI with documented DAI. Susceptibility Weighted Imaging sequence was administered to localize the DAI lesions. The adolescents performed a neurocognitive test-battery, addressing different aspects of executive functioning (working memory, attention, processing speed, planning ability) and their parents completed the Behavior Rating Inventory of Executive Function (BRIEF) - questionnaire. Executive performance of the TBI-group was compared with an age and gender matched control group of typically developing peers. Based on these results we focused on the Stockings of Cambridge test and the BRIEF to correlate with the total number and location of DAI. Results revealed that the anatomical distribution of DAI, especially in the corpus callosum and the deep brain nuclei, may have more implications for executive functioning than the total amount of DAI in adolescents. Results of this study may help guide targeted rehabilitation to redirect the disturbed development of executive function in adolescents with TBI.

Prefrontal and temporal cortical thickness in adolescents with traumatic brain injury.

AIM: To investigate the impact of traumatic injury on the developing prefrontal-temporal adolescent cortex, and correlated brain structural measures with neurocognitive functioning. METHOD: Nineteen adolescents (12 males, 7 females, age range: 11-17y, mean 15y 8mo, standard deviation 1y 7mo, median 15y 11mo) with traumatic brain injury (TBI) were included. Cortical thickness of frontal and temporal lobes was assessed using magnetic resonance imaging. We correlated cortical thickness of prefrontal-temporal regions with age, time since injury, and neurocognitive functioning, and compared these results with a matched control cohort without TBI. RESULTS: We found thinner prefrontal (p=0.039) and temporal cortices (p=0.002) in adolescents with TBI compared to typically developing children. Furthermore, significant age effect was observed on the prefrontal (r=-0.75, p=0.003) and temporal (r=-0.66, p=0.013) cortical thickness in typically developing adolescents, but not in adolescents with TBI. Executive function (measured using the Behaviour Rating Inventory of Executive Function questionnaire, with lower scores meaning higher functioning) was correlated with prefrontal cortical thickness in typically developing adolescents (r=0.72, p=0.009). Opposite trends were found for correlations between cortical thickness and executive function in the TBI and control cohort. INTERPRETATION: Structural maturation in typically developing adolescents correlates with functional development: the older the adolescent, the thinner the prefrontal cortex, the better executive function. In adolescents with TBI we observed an opposite trend, that appeared significantly different from the control group: the thinner the prefrontal and temporal cortex, the worse executive functioning. WHAT THIS PAPER ADDS: Cortical thickness is negatively correlated with age in typically developing adolescents. Prefrontal cortex thickness correlates negatively with executive function in typically developing adolescents. Correlations between cortical thickness and executive functioning rise for adolescents without traumatic brain injury (TBI). Correlations between cortical thickness and executive functioning fall for adolescents with TBI. Adolescents with TBI have a long-term impairment of adaptive functioning in daily living.

ESPESOR CORTICAL PREFRONTAL Y TEMPORAL EN ADOLESCENTES CON LESIÓN CEREBRAL TRAUMÁTICA: OBJETIVO: Investigar el impacto de la lesión traumática en el desarrollo de la corteza prefrontal-temporal en adolescentes y las medidas estructurales cerebrales correlacionadas con el funcionamiento neurocognitivo. MÉTODO: Diecinueve adolescentes (12 varones, siete mujeres, rango de edad: 11-17 años, media: 15 años 8 meses, desviación estándar: 1 años 7 meses, mediana: 15 años 11 meses) con lesión cerebral traumática (LCT). El grosor cortical de los lóbulos frontal y temporal se evaluó mediante imágenes de resonancia magnética. Se correlacionó el grosor cortical de las regiones prefrontal-temporales con la edad, el tiempo transcurrido desde la lesión y el funcionamiento neurocognitivo, y se compararon estos resultados con una cohorte de control emparejada sin TCE. RESULTADOS: Encontramos cortezas prefrontales (p = 0.039) y corticales temporales delgadas (p = 0.002) en adolescentes con LCT en comparación con niños con desarrollo típico. Además, se observó un efecto significativo de la edad en el grosor cortical prefrontal (r = -0.75, p = 0.003) y temporal (r = -0.66, p = 0.013) en adolescentes de desarrollo típico, pero no en adolescentes con LCT. La función ejecutiva (medida con el cuestionario Inventario de clasificación de la conducta de la función ejecutiva, con puntuaciones más bajas que significan un funcionamiento más alto) se correlacionó con el grosor cortical prefrontal en adolescentes con desarrollo típico (r = 0.72, p = 0.009). Se encontraron tendencias opuestas para las correlaciones entre el grosor cortical y la función ejecutiva en el LCT y la cohorte de control. INTERPRETACIÓN: La maduración estructural en adolescentes con desarrollo típico se correlaciona con el desarrollo funcional: cuanto mayor es el adolescente, más delgada es la corteza prefrontal, y mejor la función ejecutiva. En adolescentes con LCT observamos una tendencia opuesta, que parecía significativamente diferente del grupo de control: cuanto más delgada era la corteza prefrontal y temporal, peor el funcionamiento ejecutivo.

ESPESSURA PRÉ-FRONTAL E TEMPORAL EM ADOLESCENTES COM LESÃO CEREBRAL TRAUMÁTICA: OBJETIVO: Investigar o impacto da lesão cerebral traumática no córtex pré-frontal -temporal em desenvolvimento de adolescentes, e medidas cerebrais estruturais correlacionadas com o funcionamento cognitivo. MÉTODO: Dezenove adolescentes (12 do sexo masculino, sete do sexo feminino, variação de idade: 11-17a, média: 15a 8m, desvio padrão: 1a 7m, mediana: 15a 11m) com lesão cerebral traumática (LCT) foram incluídos. A espessura cortical dos lobos frontais e temporais foi avaliada usando ressonância magnética funcional. Correlacionamos a espessura cortical de regiões pré-frontais-temporais com a idade, tempo após a lesão, e funcionamento neurocognitivo, e comparamos estes resultados com uma coorte controle pareada, sem LCT. RESULTADOS: Encontramos córtex pré-frontal (p=0,039) e temporal (p=0,002) mais finos em adolescentes com LCT. Além disso, efeito significativo da idade foi observado na espessura pré-frontal (r=-0,75, p=0,003) e temporal (r=-0,66, p=0,013) em adolescentes com desenvolvimento típico, mas não nos com LCT. A função executiva (mensurada com o questionário Inventário de pontuação do comportamento da Função Executiva, com menor pontuação indicando maior funcionamento) foi correlacionada com a espessura cortical pré-frontal em adolescentes com desenvolvimento típico (r=0,72, p=0,009). Tendências opostas para as correlações entre espessura cortical e função executiva foram encontradas nas coortes com LCT e controle. INTERPRETAÇÃO: A maturação estrutural em adolescentes com desenvolvimento típico se correlaciona com o desenvolvimento functional: quanto mais velho o adolescente, mais fino o córtex e melhor a função executiva. Em adolescents com LCT observamos a tendência oposta, que foi significantemente diferente do grupo controle: quanto mais fino o córtex pré-frontal e temporal, pior a função cognitiva.

Cognitive training benefit depends on brain injury location in adolescents with traumatic brain injury: a pilot study.

BACKGROUND: Executive dysfunction after pediatric traumatic brain injury (TBI) has been linked to poor outcomes in school performance, social functioning and employment. The credibility of training-induced cognitive enhancement in TBI is threatened by its limited proof of benefit in executive skills of daily living. AIM: Our primary aim was to investigate if cognitive intervention for improving impairments in executive functions in the chronic stage of TBI is effective during adolescence. The secondary aim was to explore whether training benefit is driven by injury location. DESIGN: Prospective observational study. SETTING: Child Rehabilitation Center of a University Hospital. POPULATION: Sixteen adolescents with moderate to severe TBI (mean age 15 years and 8 months) and 16 age and gender matched healthy peers were included. METHODS: Effects of a new cognitive training program (BrainGames) were assessed postintervention and 6 months later utilizing a comprehensive neuropsychological test-battery and the Behavior Rating Inventory of Executive Function. In addition, subgroup analyses were performed to determine long-term training benefit in the presence of lesions in corpus callosum, deep-brain-nuclei and prefrontal cortex. RESULTS: Adolescents with TBI showed significant improvements on measures of executive functioning at completion of the training and at follow-up compared with the pre-tests. The presence or absence of diffuse-axonal-injuries (DAI) in the deep brain nuclei determined a significant difference in long-term training benefit. CONCLUSIONS: This study provides preliminary evidence that cognitive training, beyond the acute rehabilitation period in adolescents with TBI is effective to boost executive functioning in daily living. Furthermore, we indicated that DAI in deep brain nuclei may jeopardize long-term benefit from cognitive training. CLINICAL REHABILITATION IMPACT: Individualized rehabilitation programs are crucial in adolescents with different locations of TBI-lesions. Long term follow-up of pediatric TBI is essential.

Impaired rich club and increased local connectivity in children with traumatic brain injury: Local support for the rich?

Recent evidence has shown the presence of a "rich club" in the brain, which constitutes a core network of highly interconnected and spatially distributed brain regions, important for high-order cognitive processes. This study aimed to map the rich club organization in 17 young patients with moderate to severe TBI (15.71 ± 1.75 years) in the chronic stage of recovery and 17 age- and gender-matched controls. Probabilistic tractography was performed on diffusion weighted imaging data to construct the edges of the structural connectomes using number of streamlines as edge weight. In addition, the whole-brain network was divided into a rich club network, a local network and a feeder network connecting the latter two. Functional outcome was measured with a parent questionnaire for executive functioning. Our results revealed a significantly decreased rich club organization (p values < .05) and impaired executive functioning (p < .001) in young patients with TBI compared with controls. Specifically, we observed reduced density values in all three subnetworks (p values < .005) and a reduced mean strength in the rich club network (p = .013) together with an increased mean strength in the local network (p = .002) in patients with TBI. This study provides new insights into the nature of TBI-induced brain network alterations and supports the hypothesis that the local subnetwork tries to compensate for the biologically costly subnetwork of rich club nodes after TBI.

Brain structural and functional asymmetry in human situs inversus totalis.

Magnetic resonance imaging was used to investigate brain structural and functional asymmetries in 15 participants with complete visceral reversal (situs inversus totalis, SIT). Language-related brain structural and functional lateralization of SIT participants, including peri-Sylvian gray and white matter asymmetries and hemispheric language dominance, was similar to those of 15 control participants individually matched for sex, age, education, and handedness. In contrast, the SIT cohort showed reversal of the brain (Yakovlevian) torque (occipital petalia and occipital bending) compared to the control group. Secondary findings suggested different asymmetry patterns between SIT participants with (n = 6) or without (n = 9) primary ciliary dyskinesia (PCD, also known as Kartagener syndrome) although the small sample sizes warrant cautious interpretation. In particular, reversed brain torque was mainly due to the subgroup with PCD-unrelated SIT and this group also included 55% left handers, a ratio close to a random allocation of handedness. We conclude that complete visceral reversal has no effect on the lateralization of brain structural and functional asymmetries associated with language, but seems to reverse the typical direction of the brain torque in particular in participants that have SIT unrelated to PCD. The observed differences in asymmetry patterns of SIT groups with and without PCD seem to suggest that symmetry breaking of visceral laterality, brain torque, and language dominance rely on different mechanisms.

Mapping the functional connectome in traumatic brain injury: What can graph metrics tell us?

OBJECTIVE: Traumatic brain injury (TBI) is associated with cognitive and motor deficits, and poses a significant personal, societal, and economic burden. One mechanism by which TBI is thought to affect cognition and behavior is through changes in functional connectivity. Graph theory is a powerful framework for quantifying topological features of neuroimaging-derived functional networks. The objective of this paper is to review studies examining functional connectivity in TBI with an emphasis on graph theoretical analysis that is proving to be valuable in uncovering network abnormalities in this condition. METHODS: We review studies that have examined TBI-related alterations in different properties of the functional brain network, including global integration, segregation, centrality and resilience. We focus on functional data using task-related fMRI or resting-state fMRI in patients with TBI of different severity and recovery phase, and consider how graph metrics may inform rehabilitation and enhance efficacy. Moreover, we outline some methodological challenges associated with the examination of functional connectivity in patients with brain injury, including the sample size, parcellation scheme used, node definition and subgroup analyses. RESULTS: The findings suggest that TBI is associated with hyperconnectivity and a suboptimal global integration, characterized by increased connectivity degree and strength and reduced efficiency of functional networks. This altered functional connectivity, also evident in other clinical populations, is attributable to diffuse white matter pathology and reductions in gray and white matter volume. These functional alterations are implicated in post-concussional symptoms, posttraumatic stress and neurocognitive dysfunction after TBI. Finally, the effects of focal lesions have been found to depend critically on topological position and their role in the network. CONCLUSION: Graph theory is a unique and powerful tool for exploring functional connectivity in brain-injured patients. One limitation is that its results do not provide specific measures about the biophysical mechanism underlying TBI. Continued work in this field will hopefully see graph metrics used as biomarkers to provide more accurate diagnosis and help guide treatment at the individual patient level.

How to Train an Injured Brain? A Pilot Feasibility Study of Home-Based Computerized Cognitive Training.

OBJECTIVE: Computerized cognitive training programs have previously shown to be effective in improving cognitive abilities in patients suffering from traumatic brain injury (TBI). These studies often focused on a single cognitive function or required expensive hardware, making it difficult to be used in a home-based environment. This pilot feasibility study aimed to evaluate the feasibility of a newly developed, home-based, computerized cognitive training program for adolescents who suffered from TBI. Additionally, feasibility of study design, procedures, and measurements were examined. DESIGN: Case series, longitudinal, pilot, feasibility intervention study with one baseline and two follow-up assessments. MATERIALS AND METHODS: Nine feasibility outcome measures and criteria for success were defined, including accessibility, training motivation/user experience, technical smoothness, training compliance, participation willingness, participation rates, loss to follow-up, assessment timescale, and assessment procedures. Five adolescent patients (four boys, mean age = 16 years 7 months, standard deviation = 9 months) with moderate to severe TBI in the chronic stage were recruited and received 8 weeks of cognitive training with BrainGames. Effect sizes (Cohen's d) were calculated to determine possible training-related effects. RESULTS: The new cognitive training intervention, BrainGames, and study design and procedures proved to be feasible; all nine feasibility outcome criteria were met during this pilot feasibility study. Estimates of effect sizes showed small to very large effects on cognitive measures and questionnaires, which were retained after 6 months. CONCLUSION: Our pilot study shows that a longitudinal intervention study comprising our novel, computerized cognitive training program and two follow-up assessments is feasible in adolescents suffering from TBI in the chronic stage. Future studies with larger sample sizes will evaluate training-related effects on cognitive functions and underlying brain structures.