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Sustaining a traumatic brain injury (TBI) during adolescence has a profound effect on brain development and can result in persistent executive functioning deficits in daily life. Cognitive recovery from pediatric-TBI relies on the potential of neuroplasticity, which can be fostered by restorative training-programs. However the structural mechanisms underlying cognitive recovery in the immature brain are poorly understood. This study investigated gray matter plasticity following 2 months of cognitive training in young patients with TBI. Sixteen adolescents in the chronic stage of moderate-severe-TBI (9 male, mean age = 15y8m ± 1y7m) were enrolled in a cognitive computerized training program for 8 weeks (5 times/week, 40 min/session). Pre-and post-intervention, and 6 months after completion of the training, participants underwent a comprehensive neurocognitive test-battery and anatomical Magnetic Resonance Imaging scans. We selected 9 cortical-subcortical Regions-Of-Interest associated with Executive Functioning (EF-ROIs) and 3 control regions from the Desikan-Killiany atlas. Baseline analyses showed significant decreased gray matter density in the superior frontal gyri p = 0.033, superior parietal gyri p = 0.015 and thalamus p = 0.006 in adolescents with TBI compared to age and gender matched controls. Linear mixed model analyses of longitudinal volumetric data of the EF-ROI revealed no strong evidence of training-related changes in the group with TBI. However, compared to the change over time in the control regions between post-intervention and 6 months follow-up, the change in the EF-ROIs showed a significant difference. Exploratory analyses revealed a negative correlation between the change on the Digit Symbol Substitution test and the change in volume of the putamen (r = −0.596, p = 0.015). This preliminary study contributes to the insights of training-related plasticity mechanisms after pediatric-TBI. Keywords: Pediatric traumatic brain injury, Cognitive rehabilitation, Gray matter, Neural plasticity, Executive function, Linear mixed model analyses

Abstract Background The right hemisphere may play an important role in paralinguistic features such as the emotional melody in speech. The extent of this involvement however is unclear. Imaging studies have shown involvement of both left and right inferior frontal gyri in emotional prosody perception. The present pilot study examined whether these brain areas are critically involved in the processing of emotional prosody and of semantics in 9 healthy subjects. Repetitive transcranial magnetic stimulation was used with a coil centred over left and right inferior frontal gyri, as localized by neuronavigation based on the subject's MRI. A sham condition was included. An online-TMS approach was applied; an emotional language task was completed during stimulation. This computerized task consisted of sentences pronounced by actors. In the semantics condition an emotion (fear, anger or neutral) was expressed in the content pronounced with a neutral intonation. In the prosody condition the emotion was expressed in the intonation, while the content was neutral. Results Reaction times on the emotional prosody task condition were significantly longer after rTMS over both the right and the left inferior frontal gyrus as compared to sham stimulation and after controlling for learning effects associated with order of condition. When taking all emotions together, there was no difference in effect on reaction times between the right and left stimulation. For the emotion Fear, reaction times were significantly longer after stimulating the left inferior frontal gyrus as compared to the right inferior frontal gyrus. Reaction times in the semantics task condition were not significantly different between the three TMS conditions. Conclusions The data indicate a critical involvement of both the right and the left inferior frontal gyrus in emotional prosody perception. The findings of this pilot study need replication. Future studies should include more subjects and examine whether the left and right inferior frontal gyrus play a differential role and complement each other, e.g. in the integrated processing of linguistic and prosodic aspects of speech, respectively.

No two human brains are alike, and with the rise of precision medicine in neurology, we are seeing an increased emphasis on understanding the individual variability in brain structure and function that renders every brain unique. Functional and structural brain asymmetries are a fundamental principle of brain organization, and recent research suggests substantial individual variability in these asymmetries that needs to be considered in clinical practice. In this Review, we provide an overview of brain asymmetries, variations in such asymmetries and their relevance in the clinical context. We review recent findings on brain asymmetries in neuropsychiatric and neurodevelopmental disorders, as well as in specific learning disabilities, with an emphasis on large-scale database studies and meta-analyses. We also highlight the relevance of asymmetries for disease symptom onset in neurodegenerative diseases and their implications for lateralized treatments, including brain stimulation. We conclude that alterations in brain asymmetry are not sufficiently specific to act as diagnostic biomarkers but can serve as meaningful symptom or treatment response biomarkers in certain contexts. On the basis of these insights, we provide several recommendations for neurological clinical practice., (© 2024. Springer Nature Limited.)

Aim: To assess the impact of neonatal brachial plexus palsy (NBPP) on higher-order hand representation., Method: Eighty-two left-handed children and adolescents with and without right-sided NBPP were recruited. Thirty-one participants with NBPP (mean age [SD] 11y 4mo [4y 4mo]; age range 6y 2mo-21y 0mo; 15 females; C5-6, n=4, C5-7, n=12, C5-T1, n=11, C5-T1 with Horner sign, n=4) were assessed along with 30 controls (mean age 11y 5mo [4y 4mo]; age range 6y 7mo-21y 7mo; 14 females). Participants' estimated hand size and shape on measure of implicit and explicit hand representation was assessed. A linear mixed model (LMM) was used to investigate the effect of condition, sensorimotor impairment, and age., Results: Individuals with NBPP showed a significant difference in implicit hand representation between affected and non-affected hands. LMM confirmed a significant influence of the severity of sensorimotor injury. Only the estimated implicit hand representation was associated with age, with a significant difference between 6- to 8-year-olds and 9- to 10-year-olds., Interpretation: The effect of sensorimotor impairment on central hand representation in individuals with NBPP is specific due to its implicit component and is characterized by finger length underestimation in the affected hand compared to the characteristic underestimation in the unaffected hand. Neither NBPP nor age impacted the explicit hand estimate. This study confirms the importance of sensorimotor contribution to the development of implicit hand representation., (© 2021 Mac Keith Press.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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.

Aim: To provide a comprehensive update on the most prevalent, significant risk factors for neonatal brachial plexus palsy (NBPP)., Method: Cochrane CENTRAL, MEDLINE, Web of Science, Embase, and ClinicalTrials.gov were searched for relevant publications up to March 2019. Studies assessing risk factors of NBPP in relation to typically developing comparison individuals were included. Meta-analysis was performed for the five most significant risk factors, on the basis of the PRISMA statement and MOOSE guidelines. Pooled odds ratios (ORs), 95% confidence intervals (CIs), and across-study heterogeneity (I 2 ) were reported. Reporting bias and quality of evidence was rated. In addition, we assessed the incidence of NBPP., Results: Twenty-two observational studies with a total sample size of 29 419 037 live births were selected. Significant risk factors included shoulder dystocia (OR 115.27; 95% CI 81.35-163.35; I 2 =92%), macrosomia (OR 9.75; 95% CI 8.29-11.46; I 2 =70%), (gestational) diabetes (OR 5.33; 95% CI 3.77-7.55; I 2 =59%), instrumental delivery (OR 3.8; 95% CI 2.77-5.23; I 2 =77%), and breech delivery (OR 2.49; 95% CI 1.67-3.7; I 2 =70%). Caesarean section appeared as a protective factor (OR 0.13; 95% CI 0.11-0.16; I 2 =41%). The pooled overall incidence of NBPP was 1.74 per 1000 live births. It has decreased in recent years., Interpretation: The incidence of NBPP is decreasing. Shoulder dystocia, macrosomia, maternal diabetes, instrumental delivery, and breech delivery are risk factors for NBPP. Caesarean section appears as a protective factor., What This Paper Adds: The overall incidence of neonatal brachial plexus palsy is 1.74 per 1000 live births. The incidence has declined significantly. Shoulder dystocia, macrosomia, maternal diabetes, instrumental delivery, and breech delivery are the main risk factors. Prevention is difficult owing to unpredictability and often labour-related risk., (© 2019 Mac Keith Press.)

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., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Situs inversus (SI), a left-right mirror reversal of the visceral organs, can occur with recessive Primary Ciliary Dyskinesia (PCD). However, most people with SI do not have PCD, and the etiology of their condition remains poorly studied. We sequenced the genomes of 15 people with SI, of which six had PCD, as well as 15 controls. Subjects with non-PCD SI in this sample had an elevated rate of left-handedness (five out of nine), which suggested possible developmental mechanisms linking brain and body laterality. The six SI subjects with PCD all had likely recessive mutations in genes already known to cause PCD. Two non-PCD SI cases also had recessive mutations in known PCD genes, suggesting reduced penetrance for PCD in some SI cases. One non-PCD SI case had recessive mutations in PKD1L1, and another in CFAP52 (also known as WDR16). Both of these genes have previously been linked to SI without PCD. However, five of the nine non-PCD SI cases, including three of the left-handers in this dataset, had no obvious monogenic basis for their condition. Environmental influences, or possible random effects in early development, must be considered.

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.

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., (© 2018 Mac Keith Press.)

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., (© 2018 Wiley Periodicals, Inc.)

Background: Mental practice with motor imagery has been shown to promote motor skill acquisition in healthy subjects and patients. Although lesions of the common motor imagery and motor execution neural network are expected to impair motor imagery ability, functional equivalence appears to be at least partially preserved in stroke patients., Aim: To identify brain regions that are mandatory for preserved motor imagery ability after stroke., Method: Thirty-seven patients with hemiplegia after a first time stroke participated. Motor imagery ability was measured using a Motor Imagery questionnaire and temporal congruence test. A voxelwise lesion symptom mapping approach was used to identify neural correlates of motor imagery in this cohort within the first year post-stroke., Results: Poor motor imagery vividness was associated with lesions in the left putamen, left ventral premotor cortex and long association fibers linking parieto-occipital regions with the dorsolateral premotor and prefrontal areas. Poor temporal congruence was otherwise linked to lesions in the more rostrally located white matter of the superior corona radiata., Conclusion: This voxel-based lesion symptom mapping study confirms the association between white matter tract lesions and impaired motor imagery ability, thus emphasizing the importance of an intact fronto-parietal network for motor imagery. Our results further highlight the crucial role of the basal ganglia and premotor cortex when performing motor imagery tasks.

Objectives: To assess the long-term neuropsychological and behavioural profile of school-aged children who were treated for univentricular heart (UVH) conditions or biventricular heart defect (BiVH) in infancy in a cross-sectional study design., Methods: Sixty-three patients, 17 UVH (13 males, 4 females) and 46 BiVH (19 males, 27 females), were assessed at a mean age of 9.1 years (2.2 years) with an intelligence and neuropsychological test battery. Results were compared between subgroups (UVH, BiVH and a healthy control group). Associations between cognitive outcome, medical and socio-demographic factors were explored. Parents completed the Child Behavior Checklist (CBCL)., Results: Mean intelligence and neuropsychological scores were found within normal ranges for all diagnostic groups. Significant differences between UVH patients and controls emerged on auditory sustained and alternating attention, fine motor skills, visuospatial information processing, and to a lesser extent, memory performance. Parents of UVH patients reported more externalizing problems and school problems. Patient groups did not differ on neuropsychological outcome measures, nor on behavioural problems as rated by parents., Conclusions: After Fontan completion, patients at school age display intelligence scores within normal population-based ranges. However, they were found at risk for subtle shortcomings in attention, fine motor skills, visuospatial information processing and externalizing behaviour problems. Considerations pertaining to neurobehavioural outcome in school-aged children are discussed., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Clinical research suggests that imitating meaningless hand postures and pantomiming tool-related hand shapes rely on different neuroanatomical substrates. We investigated the BOLD responses to different tasks of hand posture generation in 14 right handed volunteers. Conjunction and contrast analyses were applied to select regions that were either common or sensitive to imitation and/or pantomime tasks. The selection included bilateral areas of medial and lateral extrastriate cortex, superior and inferior regions of the lateral and medial parietal lobe, primary motor and somatosensory cortex, and left dorsolateral prefrontal, and ventral and dorsal premotor cortices. Functional connectivity analysis revealed that during hand shape generation the BOLD-response of every region correlated significantly with every other area regardless of the hand posture task performed, although some regions were more involved in some hand postures tasks than others. Based on between-task differences in functional connectivity we predict that imitation of novel hand postures would suffer most from left superior parietal disruption and that pantomiming hand postures for tools would be impaired following left frontal damage, whereas both tasks would be sensitive to inferior parietal dysfunction. We also unveiled that posterior temporal cortex is committed to pantomiming tool grips, but that the involvement of this region to the execution of hand postures in general appears limited. We conclude that the generation of hand postures is subserved by a highly interconnected task-general neural network. Depending on task requirements some nodes/connections will be more engaged than others and these task-sensitive findings are in general agreement with recent lesion studies., (© 2015 Wiley Periodicals, Inc.)

Background: The objective of this study was to review the recent literature regarding the neurocognitive consequences of carotid endarterectomy (CEA) and carotid stenting (CAS)., Methods and Results: A PubMed and Web of Science search was conducted using the key words 'carotid' in combination with 'cognitive', 'cognition', 'neurocognition', 'neurocognitive', 'neuropsychology', and 'neuropsychological'. Bibliographies of relevant articles were cross-referenced. We included 37 studies published since 2007 of which 18 examined CEA, 12 CAS, and 7 compared CEA to CAS. There is a wide variability in the reported neurocognitive outcome following CEA and CAS. Nonetheless, none of the included studies unveiled significant differences between CEA and CAS on postoperative neurocognitive functioning. Postoperative changes observed for CEA and CAS separately seem limited to a small percentage (around 10-15%) of patients and can either present as an improvement or impairment., Key Messages: The available data seem to suggest that no obvious cognitive differences between CAS and CEA can be observed after intervention. Both improvement and deterioration in cognitive functioning can be observed following CAS or CEA. Methodological differences such as patient heterogeneity, implementation and type of control groups, type of psychometric tests used, statistical analyses, or timing of the assessments play an important role in explaining the sometimes divergent results of the included studies. Large-scale and methodologically solid studies comparing CEA and CAS on neurocognitive outcome remain warranted. Future studies should implement adequate control groups to correct for practice effects in the target groups.

Neuropsychological and neuroimaging data suggest a differential contribution of posterior parietal regions during the different components of a transitive gesture. Reaching requires the integration of object location and body position coordinates and reaching tasks elicit bilateral activation in different foci along the intraparietal sulcus. Grasping requires a visuomotor match between the object's shape and the hand's posture. Lesion studies and neuroimaging confirm the importance of the anterior part of the intraparietal sulcus for human grasping. Reaching and grasping reveal bilateral activation that is generally more prominent on the side contralateral to the hand used or the hemifield stimulated. Purposeful behavior with objects and tools can be assessed in a variety of ways, including actual use, pantomimed use, and pure imagery of manipulation. All tasks have been shown to elicit robust activation over the left parietal cortex in neuroimaging, but lesion studies have not always confirmed these findings. Compared to pantomimed or imagined gestures, actual object and tool use typically produces activation over the left primary somatosensory region. Neuroimaging studies on pantomiming or imagery of tool use in healthy volunteers revealed neural responses in possibly separate foci in the left supramarginal gyrus. In sum, the parietal contribution of reaching and grasping of objects seems to depend on a bilateral network of intraparietal foci that appear organized along gradients of sensory and effector preferences. Dorsal and medial parietal cortex appears to contribute to the online monitoring/adjusting of the ongoing prehensile action, whereas the functional use of objects and tools seems to involve the inferior lateral parietal cortex. This functional input reveals a clear left lateralized activation pattern that may be tuned to the integration of acquired knowledge in the planning and guidance of the transitive movement.

Visuomotor transformations for grasping have been associated with a fronto-parietal network in the monkey brain. The human homologue of the parietal monkey region (AIP) has been identified as the anterior part of the intraparietal sulcus (aIPS), whereas the putative human equivalent of the monkey frontal region (F5) is located in the ventral part of the premotor cortex (vPMC). Results from animal studies suggest that monkey F5 is involved in the selection of appropriate hand postures relative to the constraints of the task. In humans, the functional roles of aIPS and vPMC appear to be more complex and the relative contribution of each region to grasp selection remains uncertain. The present study aimed to identify modulation in brain areas sensitive to the difficulty level of tool object - hand posture matching. Seventeen healthy right handed participants underwent fMRI while observing pictures of familiar tool objects followed by pictures of hand postures. The task was to decide whether the hand posture matched the functional use of the previously shown object. Conditions were manipulated for level of difficulty. Compared to a picture matching control task, the tool object - hand posture matching conditions conjointly showed increased modulation in several left hemispheric regions of the superior and inferior parietal lobules (including aIPS), the middle occipital gyrus, and the inferior temporal gyrus. Comparison of hard versus easy conditions selectively modulated the left inferior frontal gyrus with peak activity located in its opercular part (Brodmann area (BA) 44). We suggest that in the human brain, vPMC/BA44 is involved in the matching of hand posture configurations in accordance with visual and functional demands.

We aimed to investigate the effect of hand effector and handedness on the cerebral lateralization of pantomiming learned movements. Fourteen right-handed and 14 left-handed volunteers performed unimanual and bimanual tool-use pantomimes with their dominant or nondominant hand during fMRI. A left hemispheric lateralization was observed in the right- and left-handed group regardless of which hand(s) performed the task. Asymmetry was most marked in the dorsolateral prefrontal cortex (DLPFC), premotor cortex (PMC), and superior and inferior parietal lobules (SPL and IPL). Unimanual pantomimes did not reveal any significant differences in asymmetric cerebral activation patterns between left- and right-handers. Bimanual pantomimes showed increased left premotor and posterior parietal activation in left- and right-handers. Lateralization indices (LI) of the 10% most active voxels in DLPFC, PMC, SPL, and IPL were calculated for each individual in a contrast that compared all tool versus all control conditions. Left-handers showed a significantly reduced overall LI compared with right-handers. This was mainly due to diminished asymmetry in the IPL and SPL. We conclude that the recollection and pantomiming of learned gestures recruits a similar left lateralized activation pattern in right and left-handed individuals. Handedness only influences the strength (not the side) of the lateralization, with left-handers showing a reduced degree of asymmetry that is most readily observed over the posterior parietal region. Together with similar findings in language and visual processing, these results point to a lesser hemispheric specialization in left-handers that may be considered in the cost/benefit assessment to explain the disproportionate handedness polymorphism in humans., (Copyright © 2011 Wiley Periodicals, Inc.)

This study aims to reveal the neural correlates of planning and executing tool use pantomimes and explores the brain's response to pantomiming the use of unfamiliar tools. Sixteen right-handed volunteers planned and executed pantomimes of equally graspable familiar and unfamiliar tools while undergoing fMRI. During the planning of these pantomimes, we found bilateral temporo-occipital and predominantly left hemispheric frontal and parietal activation. The execution of the pantomimes produced additional activation in frontal and sensorimotor regions. In the left posterior parietal region both familiar and unfamiliar tool pantomimes elicit peak activity in the anterior portion of the lateral bank of the intraparietal sulcus--A region associated with the representation of action goals. The cerebral activation during these pantomimes is remarkably similar for familiar and unfamiliar tools, and direct comparisons revealed only few differences. First, the left cuneus is significantly active during the planning of pantomimes of unfamiliar tools, reflecting increased visual processing of the novel objects. Second, executing (but not planning) familiar tool pantomimes showed significant activation on the convex portion of the inferior parietal lobule, a region believed to serve as a repository for skilled object-related gestures. Given the striking similarity in brain activation while pantomiming familiar and unfamiliar tools, we argue that normal subjects use both action semantics and function from structure inferences simultaneously and interactively to give rise to flexible object-to-goal directed behavior., (Copyright © 2010 Wiley-Liss, Inc.)

A growing number of studies show that visual mental imagery recruits the same brain areas as visual perception. Although the necessity of hV5/MT+ for motion perception has been revealed by means of TMS, its relevance for motion imagery remains unclear. We induced a direction-selective adaptation in hV5/MT+ by means of an MAE while subjects performed a mental rotation task that elicits imagined motion. We concurrently measured behavioral performance and neural activity with fMRI, enabling us to directly assess the effect of a perturbation of hV5/MT+ on other cortical areas involved in the mental rotation task. The activity in hV5/MT+ increased as more mental rotation was required, and the perturbation of hV5/MT+ affected behavioral performance as well as the neural activity in this area. Moreover, several regions in the posterior parietal cortex were also affected by this perturbation. Our results show that hV5/MT+ is required for imagined visual motion and engages in an interaction with parietal cortex during this cognitive process.

Objective: Neurocognitive sequelae after coronary artery bypass grafting (CABG) are frequently reported. The present study investigated the possible difference between on- and off-pump CABG patients in a long-term perspective., Methods: We administered seven standardized neuropsychological tests 1 day before, 6 days after, 6 months after and 3-5 years after CABG. We measured intra-operative high intensity transient signals (HITS) as a reflection of embolic load by transcranial Doppler ultrasonography., Results: Of the 74 patients originally recruited, 54 of the patients (73%) (mean age 59 years+/-7.5 years) completed the neuropsychological battery. Cognitive decline was defined as 20% decline on two or more tests. Three to 5 years after the operation, 30% of the patients showed neurocognitive problems in domains of non-verbal immediate memory and attention, speed for visual search, visual attention and mental flexibility. Neither difference in frequency of cognitive dysfunction nor a difference in evolution over the 5 year time period between on- and off-pump patients was observed. No significant predictors for cognitive decline were found., Conclusions: Three to 5 years after the CABG surgery no difference in neurocognitive deficits is found between on- and off-pump CABG patients, indicating that the extracorporeal circulation (ECC) may not be the main cause of late neuropsychological decline.

Objective: Although it is known that pediatric cardiac surgery holds risks for later development, few studies investigated the long-term development in children with tetralogy of Fallot. The purpose of this study was to define their intellectual capacities, neuropsychological profile, and behavioral functioning 6 to 12 years postoperatively., Methods: Patients (n = 18; age, 8 years, 3 months +/- 1 year, 6 months) were examined with a short-form intelligence scale (Wechsler Intelligence Scale for Children, 3rd edition, Dutch version) and a neuropsychological assessment battery (NEPSY). Their parents completed a behavioral questionnaire. The patient group was compared with an acyanotic congenital heart disease group and a healthy control group., Results: No significant differences between the patient group and the acyanotic group emerged. Compared with the healthy control group, children with tetralogy of Fallot showed significantly lower scores on the estimated Full Scale IQ (P < .05) and on the NEPSY domains Language (P < .01) and Sensorimotor Functioning (P < .01). Also, the subtests Tower (P < .05), Memory for Names (P < .05), Narrative Memory (P < .05), and Design Copy (P < .05) elicited group differences. Parental reports revealed significantly higher scores on attention problems (P < .05) and the total problem scale (P < .05), as well as significantly lower school performances than those of healthy peers (P < .01)., Conclusions: In children with tetralogy of Fallot, we identified a lower estimated full-scale intelligence than in healthy peers and a neuropsychological profile characterized by primarily mild motor deficits and difficulties with language tasks. Parents of the children with tetralogy of Fallot indicated attention problems and rated the child's school competencies to be lower than in healthy control subjects.

We aimed to review recent prospective and cross-sectional studies regarding the gradual and chronic effects of (cumulative) seizures on cognition. In contrast with the increasing evidence of structural changes in the brain associated with repeated seizures, its functional repercussions remain unclear. Methodological difficulties of cross-sectional and prospective studies are addressed. It appears that all but one of the prospective studies available on children are limited to measures of intelligence. Most studies revealed no significant adverse effects, although there appears to be a subgroup of about 10-25% of children that shows a clinically significant intellectual decline. Children with generalized symptomatic epilepsies, frequent seizures, high antiepileptic drug use, and early onset of epilepsy appear at risk, although psychosocial factors may also play an important role. Five of the six prospective studies on adults report evidence of a mild decline in cognition in patients with a (longstanding) history of pharmacoresistant epilepsy. The adverse effect on cognitive abilities, memory in particular, seems somewhat more robust than that on measures of intelligence. A significant association between cognitive decline and seizure related variables is rarely substantiated in prospective research and cross-sectional studies show contradicting results. Taken together, the data suggest a mild but measurable decline of intellectual performance in children and adults. Decline of specific cognitive abilities in children is impossible to evaluate given the very little data available. In adults, memory appears to be the most vulnerable cognitive function. Due to many confounding variables, the effect of seizures per se is difficult to estimate, but appears limited.

Neurostimulation is an emerging treatment for refractory epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond to such a treatment and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing vagus nerve stimulation (VNS). Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Deep brain stimulation (DBS) for epilepsy has regained interest. Central nervous system structures known to play a key role in the epileptogenic network such as the thalamus and subthalamic nucleus have been targeted. Another approach is to target the ictal onset zone such as the medial temporal lobe. At Ghent University Hospital 10 patients have been treated with long-term amygdalohippocampal DBS. Several hypotheses have been raised for the mechanism of action of DBS for refractory seizures. Seizure reduction may be due to a microlesion caused by electrode insertion or by provoking a reversible functional lesion due to the effect of electrical current on hyperexcitable tissue. Neurophysiological techniques such as evoked potentials monitoring and intraoperative single unit potential recordings may guide correct electrode placement, individual DBS titration and elucidation of the mechanims of action of DBS for epilepsy.

Objective: Neuropsychological dysfunctions are considered to be important complications of coronary artery bypass graft surgery (CABG). We examined the frequency of neuropsychological abnormalities occurring in patients undergoing CABG with (on-pump) and without (off-pump) cardiopulmonary bypass., Methods: Neuropsychological assessment with seven cognitive tasks was performed one day before, 6-7 days after (n=49) and 6 months after (n=35) surgery. The subgroup undergoing on-pump surgery (n=30 at 7 days and n=22 at 6 months) was demographically comparable to the off-pump subgroup. The on-pump group included more multiple vessel disease., Results: Repeated measures multivariate analysis of variance (using surgical group as a between-subjects factor) on the group data revealed no significant differences neither immediately after surgery nor at 6 months after surgery, compared with the preoperative performance. There were no significant differences between the on-pump and off-pump groups in post-operative neuropsychological performance soon after surgery. A significant difference was found between the two groups 6 months after surgery, with more favorable results for the off-pump group. Individual comparisons revealed that 59% of the patients of both groups undergoing CABG showed evidence of cognitive impairment soon after surgery. In 11% of the patients (all on-pump), the cognitive sequelae persisted at follow-up., Conclusion: This study showed no short-term difference between the on-pump and off-pump CABG groups. The long-term cognitive outcome revealed more favorable results for the off-pump group. Although a preference to operate multiple vessel disease with classical cardiopulmonary bypass (CPB) has to be considered, the present study shows evidence for a different pattern of early decline and late recovery of cognitive functions in patients undergoing CABG with and without CPB.