Determinants of IQ outcome after focal epilepsy surgery in childhood: A longitudinal case-control neuroimaging study.

OBJECTIVE: Intelligence quotient (IQ) outcomes after pediatric epilepsy surgery show significant individual variation. Clinical factors such as seizure cessation or antiepileptic medication discontinuation have been implicated, but do not fully account for the heterogeneity seen. Less is known about the impact of neurobiological factors, such as brain development and resection location. This study examines clinical and neuroimaging factors associated with cognitive outcome after epilepsy surgery in childhood. METHODS: Fifty-two children (28 boys, 24 girls) were evaluated for epilepsy surgery and reassessed on average 7.7 years later. In the intervening time, 13 were treated pharmacologically and 39 underwent focal surgery (17 temporal, 16 extratemporal, six multilobar; mean age at surgery = 14.0 years). Pre- and postsurgical assessments included IQ tests and T1-weighted brain images. Predictors of IQ change were investigated, including voxel-based analyses of resection location, and gray and white matter volume change. RESULTS: Overall modest IQ improvement was seen in children treated surgically, but not in those treated pharmacologically only. Applying a ≥10-point change threshold, 39% of the surgically treated children improved, whereas 10% declined. Clinical factors associated with IQ increases were lower preoperative IQ and longer follow-up duration, whereas seizure and antiepileptic medication cessation were not predictive. Among neuroimaging factors, we observed that left anterior temporal resections impacted negatively on verbal reasoning, linked to full-scale IQ decline. In contrast, gray matter volume change in ipsi- and contralesional hemispheres was positively correlated with IQ change. Voxel-based morphometry identified the gray matter volume change in the contralesional dorsolateral frontal cortex as most strongly associated with IQ improvement. SIGNIFICANCE: We show that a variety of factors are likely to contribute to patterns of postsurgical change in IQ. Neuroimaging results indicate that left anterior temporal resections constrain development of verbal cognition, whereas simultaneously cortical growth after surgical treatment can support improvements in IQ.

Cardiovascular disease risk marker responses to breaking up prolonged sedentary time in individuals with paraplegia: the Spinal Cord Injury Move More (SCIMM) randomised crossover laboratory trial protocol.

INTRODUCTION: Sedentary behaviour is a distinct risk factor for cardiovascular disease (CVD) and could partly explain the increased prevalence of CVD in people with spinal cord injury (SCI). Interrupting prolonged sitting periods with regular short bouts of walking acutely suppresses postprandial glucose and lipids in able-bodied individuals. However, the acute CVD risk marker response to breaking up prolonged sedentary time in people with SCI has not been investigated. METHODS AND ANALYSIS: A randomised two-condition laboratory crossover trial will compare: (1) breaking up prolonged sedentary time with 2 min moderate-intensity arm-crank activity every 20 min, with (2) uninterrupted prolonged sedentary time (control) in people with SCI. Outcomes will include acute effects on postprandial glucose, insulin, lipids and blood pressure. Blood samples will be collected and blood pressure measured at regular intervals during each 5½-hour condition. ETHICS AND DISSEMINATION: This study was approved by the Cambridge South National Health Service Research Ethics Committee. This research will help determine if breaking up prolonged sedentary time could be effective in lowering CVD risk in people with SCI. The findings of the research will be published in a peer-reviewed journal and disseminated to relevant user groups. TRIAL REGISTRATION NUMBER: ISRCTN51868437; Pre-results.

Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy.

OBJECTIVES: The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. METHODS: The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. RESULTS: The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. SIGNIFICANCE: Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology.

FIACH: A biophysical model for automatic retrospective noise control in fMRI.

Different noise sources in fMRI acquisition can lead to spurious false positives and reduced sensitivity. We have developed a biophysically-based model (named FIACH: Functional Image Artefact Correction Heuristic) which extends current retrospective noise control methods in fMRI. FIACH can be applied to both General Linear Model (GLM) and resting state functional connectivity MRI (rs-fcMRI) studies. FIACH is a two-step procedure involving the identification and correction of non-physiological large amplitude temporal signal changes and spatial regions of high temporal instability. We have demonstrated its efficacy in a sample of 42 healthy children while performing language tasks that include overt speech with known activations. We demonstrate large improvements in sensitivity when FIACH is compared with current methods of retrospective correction. FIACH reduces the confounding effects of noise and increases the study's power by explaining significant variance that is not contained within the commonly used motion parameters. The method is particularly useful in detecting activations in inferior temporal regions which have proven problematic for fMRI. We have shown greater reproducibility and robustness of fMRI responses using FIACH in the context of task induced motion. In a clinical setting this will translate to increasing the reliability and sensitivity of fMRI used for the identification of language lateralisation and eloquent cortex. FIACH can benefit studies of cognitive development in young children, patient populations and older adults.

Maturation of language networks in children: A systematic review of 22years of functional MRI.

Understanding how language networks change during childhood is important for theories of cognitive development and for identifying the neural causes of language impairment. Despite this, there is currently little systematic evidence regarding the typical developmental trajectory for language from the field of neuroimaging. We reviewed functional MRI (fMRI) studies published between 1992 and 2014, and quantified the evidence for age-related changes in localisation and lateralisation of fMRI activation in the language network (excluding the cerebellum and subcortical regions). Although age-related changes differed according to task type and input modality, we identified four consistent findings concerning the typical maturation of the language system. First, activation in core semantic processing regions increases with age. Second, activation in lower-level sensory and motor regions increases with age as activation in higher-level control regions reduces. We suggest that this reflects increased automaticity of language processing as children become more proficient. Third, the posterior cingulate cortex and precuneus (regions associated with the default mode network) show increasing attenuation across childhood and adolescence. Finally, language lateralisation is established by approximately 5years of age. Small increases in leftward lateralisation are observed in frontal regions, but these are tightly linked to performance.

Reduced language connectivity in pediatric epilepsy.

OBJECTIVE: Functional connectivity (FC) among language regions is decreased in adults with epilepsy compared to controls, but less is known about FC in children with epilepsy. We sought to determine if language FC is reduced in pediatric epilepsy, and examined clinical factors that associate with language FC in this population. METHODS: We assessed FC during an age-adjusted language task in children with left-hemisphere focal epilepsy (n = 19) compared to controls (n = 19). Time series data were extracted for three left regions of interest (ROIS) and their right homologues: inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and Wernicke's area (WA) using SPM8. Associations between FC and factors such as cognitive performance, language dominance, and epilepsy duration were assessed. RESULTS: Children with epilepsy showed decreased interhemispheric connectivity compared to controls, particularly between core left language regions (IFG, WA) and their right hemisphere homologues, as well as decreased intrahemispheric right frontal FC. Increased intrahemispheric FC between left IFG and left WA was a positive predictor of language skills overall, and naming ability in particular. FC of language areas was not affected by language dominance, as the effects remained only when examining participants with left language dominance. Overall FC did not differ according to duration of epilepsy or age of onset. SIGNIFICANCE: FC during a language task is reduced in children, similar to findings in adults. In specific, children with left focal epilepsy demonstrated decreased interhemispheric FC in temporal and frontal language connections and decreased intrahemispheric right frontal FC. These differences were present near the onset of epilepsy. Greater FC between left language centers is related to better language ability. Our results highlight that connectivity of language areas has a developmental pattern and is related to cognitive ability.

Vulnerability of the ventral language network in children with focal epilepsy.

Children with focal epilepsy are at increased risk of language impairment, yet the neural substrate of this dysfunction is not yet known. Using functional magnetic resonance imaging we investigated the impact of focal epilepsy on the developing language system using measures of network topology (spatial organization of activation) and synchrony (functional connectivity). We studied healthy children (n = 48, 4-12 years, 24 females) and children with focal epilepsy (n = 21, 5-12 years, nine females) with left hemisphere language dominance. Participants performed an age-adjusted auditory description decision task during functional magnetic resonance imaging, to identify perisylvian language regions. Mean signal change was extracted from eight left perisylvian regions of interest and compared between groups. Paired region of interest functional connectivity analysis was performed on time course data from the same regions, to investigate left network synchrony. Two principal component analyses were performed to extract (i) patterns of activation (using mean signal change data); and (ii) patterns of synchronized regions (using functional connectivity data). For both principal component analyses two components (networks) were extracted, which mapped onto the functional anatomy of dorsal and ventral language systems. Associations among network variables, age, epilepsy-related factors and verbal ability were assessed. Activated networks were affected by age and epilepsy [F(2,60) = 3.74, P = 0.03]: post hoc analyses showed, for healthy children, activation in both ventral and dorsal networks decreased with age (P = 0.02). Regardless of age and task performance, children with epilepsy showed reduced activation of the ventral network (P < 0.001). They also showed a trend for increased activation of the dorsal network (P = 0.08) associated with improved task performance (r = 0.62, P = 0.008). Crucially, decreased activation of the ventral network in patients predicted poorer language outcome ([Formula: see text] = 0.47, P = 0.002). This suggests childhood onset epilepsy preferentially alters maturation of the ventral language system, and this is related to poorer language ability.

Asymmetry of planum temporale constrains interhemispheric language plasticity in children with focal epilepsy.

Reorganization of eloquent cortex enables rescue of language functions in patients who sustain brain injury. Individuals with left-sided, early-onset focal epilepsy often show atypical (i.e. bilateral or right-sided) language dominance. Surprisingly, many patients fail to show such interhemispheric shift of language despite having major epileptogenic lesions in close proximity to eloquent cortex. Although a number of epilepsy-related factors may promote interhemispheric plasticity, it has remained unexplored if neuroanatomical asymmetries linked to human language dominance modify the likelihood of atypical lateralization. Here we examined the asymmetry of the planum temporale, one of the most striking asymmetries in the human brain, in relation to language lateralization in children with left-sided focal epilepsy. Language functional magnetic resonance imaging was performed in 51 children with focal epilepsy and left-sided lesions and 36 healthy control subjects. We examined the association of language laterality with a range of potential clinical predictors and the asymmetry of the length of the planum temporale. Using voxel-based methods, we sought to determine the effect of lesion location (in the affected left hemisphere) and grey matter density (in the unaffected right hemisphere) on language laterality. Atypical language lateralization was observed in 19 patients (38%) and in four controls (11%). Language laterality was increasingly right-sided in patients who showed atypical handedness, a left perisylvian ictal electroencephalographic focus, and a lesion in left anterior superior temporal or inferior frontal regions. Most striking was the relationship between rightward asymmetry of the planum temporale and atypical language (R = 0.70, P < 0.0001); patients with a longer planum temporale in the right (unaffected) hemisphere were more likely to have atypical language dominance. Voxel-based regression analysis confirmed that increased grey matter density in the right temporo-parietal junction was correlated with right hemisphere lateralization of language. The length of the planum temporale in the right hemisphere was the main predictor of language lateralization in the epilepsy group, accounting for 48% of variance, with handedness accounting for only a further 5%. There was no correlation between language lateralization and planum temporale asymmetry in the control group. We conclude that asymmetry of the planum temporale may be unrelated to language lateralization in healthy individuals, but the size of the right, contra-lesional planum temporale region may reflect a 'reserve capacity' for interhemispheric language reorganization in the presence of a seizure focus and lesions within left perisylvian regions.

Interhemispheric temporal lobe connectivity predicts language impairment in adolescents born preterm.

Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses showed that a combination of anatomical measures of temporal interhemispheric connectivity (through the splenium of the corpus callosum and anterior commissure) explained 57% of the variance in language abilities. This supports recent theories emphasizing the importance of interhemispheric connections for language, particularly in the developing brain.

The effect of carbohydrate-electrolyte beverage drinking strategy on 10-mile running performance.

The purpose of the current study was to investigate the influence of ingesting a carbohydrate-electrolyte (CHO-E) beverage ad libitum or as a prescribed volume on 10-mile run performance and gastrointestinal (GI) discomfort. Nine male recreational runners completed the 10-mile run under the following 3 conditions: no drinking (ND; 0 ml, 0 g CHO), ad libitum drinking (AD; 315 ± 123 ml, 19 ± 7 g CHO), and prescribed drinking (PD; 1,055 ± 90 ml, 64 ± 5 g CHO). During the AD and PD trials, drinks were provided on completion of Miles 2, 4, 6, and 8. Running performance, speed (km/hr), and 10-mile run time were assessed using a global positioning satellite system. The runners' ratings of perceived exertion and GI comfort were recorded on completion of each lap of the 10-mile run. There was a significant difference (p < .10) in performance times for the 10-mile race for the ND, AD, and PD trials, which were 72:05 ± 3:36, 71:14 ± 3:35, and 72:12 ± 3.53 min:s, respectively (p = .094). Ratings of GI comfort were reduced during the PD trial in comparison with both AD and ND trials. In conclusion, runners unaccustomed to habitually drinking CHO-E beverages during training improved their 10-mile race performance with AD drinking a CHO-E beverage, in comparison with drinking a prescribed volume of the same beverage or no drinking.

A comparison of the physiological demands of wheelchair basketball and wheelchair tennis.

PURPOSE: To examine the physiological profiles of wheelchair basketball and tennis and specifically to: (a) identify if there are differences in the physiological profiles of wheelchair basketball and tennis players of a similar playing standard, (b) to determine whether the competitive physiological demands of these sports differed (c) and to explore the relationship between the blood lactate [Bla-] response to exercise and to identify the sport specific heart rate (HR) training zones. METHODS: Six elite athletes (4 male, 2 female) from each sport performed a submaximal and VO2peak test in their sport specific wheelchair. Heart rate, VO2, and [Bla-] were measured. Heart rate was monitored during international competitions and VO2 was calculated from this using linear regression equations. Individual HR training zones were identified from the [Bla-] profile and time spent within these zones was calculated for each match. RESULTS: Despite no differences in the laboratory assessment of HRpeak, the VO2peak was higher for the basketball players when compared with the tennis players (2.98 ± 0.91 vs 2.06 ± 0.71; P = .08). Average match HR (163 ± 11 vs 146 ± 16 beats x min(-1); P = .06) and average VO2 (2.26 ± 0.06 vs 1.36 ± 0.42 L x min(-1); P = .02) were higher during actual playing time of basketball when compared with whole tennis play. Consequently, differences in the time spent in the different training zones within and between the two sports existed (P < .05). CONCLUSIONS: Wheelchair basketball requires predominately high-intensity training, whereas tennis training requires training across the exercise intensity spectrum.

High-intensity interval training attenuates the exercise-induced increase in plasma IL-6 in response to acute exercise.

This aims of this study were to investigate the effects of carbohydrate availability during endurance training on the plasma interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha response to a subsequent acute bout of high-intensity interval exercise. Three groups of recreationally active males performed 6 weeks of high-intensity interval running. Groups 1 (LOW+GLU) and 2 (LOW+PLA) trained twice per day, 2 days per week, and consumed a 6.4% glucose or placebo solution, respectively, before every second training session and at regular intervals throughout exercise. Group 3 (NORM) trained once per day, 4 days per week, and consumed no beverage during training. Each group performed 50 min of high-intensity interval running at the same absolute workloads before and after training. Muscle glycogen utilization in the gastrocnemius muscle during acute exercise was reduced (p < 0.05) in all groups following training, although this was not affected by training condition. Plasma IL-6 concentration increased (p < 0.05) after acute exercise in all groups before and after training. Furthermore, the magnitude of increase was reduced (p < 0.05) following training. This training-induced attenuation in plasma IL-6 increase was similar among groups. Plasma IL-8 concentration increased (p < 0.05) after acute exercise in all groups, although the magnitude of increase was not affected (p > 0.05) by training. Acute exercise did not increase (p > 0.05) plasma TNF-alpha when undertaken before or after training. Data demonstrate that the exercise-induced increase in plasma IL-6 concentration in response to customary exercise is attenuated by previous exercise training, and that this attenuation appears to occur independent of carbohydrate availability during training.

Reduced carbohydrate availability does not modulate training-induced heat shock protein adaptations but does upregulate oxidative enzyme activity in human skeletal muscle.

The primary aim of the present study was to test the hypothesis that training with reduced carbohydrate availability from both endogenous and exogenous sources provides an enhanced stimulus for training-induced heat shock protein (HSP) adaptations of skeletal muscle. A secondary aim was to investigate the influence of reduced carbohydrate availability on oxidative adaptations and exercise performance. Three groups of recreationally active men performed 6 wk of high-intensity intermittent running occurring four times per week. Group 1 (n = 8; Low + Glu) and 2 (n = 7; Low + Pla) trained twice per day, 2 days/wk, and consumed a 6.4% glucose or placebo solution, respectively, immediately before every second training session and at regular intervals throughout exercise. Group 3 (n = 8; Norm) trained once per day, 4 days/wk, and consumed no beverage throughout training. Training induced significant improvements in maximal oxygen uptake (Vo(2max)) (P = 0.001) and distance covered on Yo-Yo Intermittent Recovery Test 2 (P = 0.001) in all groups, with no difference between conditions. Similarly, training resulted in significant increases in HSP70, HSP60, and alphaB-crystallin in the gastrocnemius (P = 0.03, 0.02, and 0.01, respectively) and vastus lateralis (P = 0.01, 0.02, and 0.003, respectively) muscles in all groups, with no difference between conditions. In contrast, training resulted in significant increases in succinate dehydrogenase (SDH) activity of the gastrocnemeius (Low + Glu, Low + Pla, and Norm: 27, 76, and 53% increases, respectively; P = 0.001) and vastus lateralis muscles (Low + Glu, Low + Pla, and Norm: 17, 70, and 19% increases, respectively; P = 0.001) where the magnitude of increase in SDH activity was significantly larger for both muscles (P = 0.03 and 0.04 for gastrocnemius and vastus lateralis, respectively) for subjects training in the Low + Pla condition. Data provide the first evidence that in whole body exercise conditions, carbohydrate availability appears to have no modulating effect on training-induced increases of the HSP content of skeletal muscle. In contrast, training under conditions of reduced carbohydrate availability from both endogenous and exogenous sources provides an enhanced stimulus for inducing oxidative enzyme adaptations of skeletal muscle although this does not translate to improved performance during high-intensity exercise.