the motor impairments observed following unilateral brain injuries are typically thought to be caused by damage to motor cortices and descending motor pathways , however , changes in other brain areas including the corpus callosum may also be a factor . specific to motor functions , the corpus callosum is necessary for bimanual coordination as well as providing interhemispheric inhibition during unimanual tasks ( fling and seidler , 2012 ; gallea et al . , 2011 ; koerte et al . , lesions in the corpus callosum have also been linked to gait disturbances including reduced step heights , wide base of support , and reduced cadence ( giroud and dumas , 1995 ) . degeneration of callosal fibers has been previously reported in adults following a stroke ( gupta et al . , 2006 ; wang et al . , 2011 ) , as well as in children with early unilateral brain injuries including stroke ( kulak et al . , 2008 ; moses et al . , 2000 ) . more specifically , in adult stroke , the degeneration of transcallosal fibers connecting higher order sensorimotor areas has been correlated with greater bilateral motor area activation during paretic hand movements and poorer motor outcomes ( wang et al . , 2011 ) . in children with hemiplegia , mirror movements and difficulties with discrete bimanual tasks are commonly reported ( kuhtz - buschbeck et al . , 2000 ; the purpose of this study was to determine if unilateral lesions occurring early in life compared to in adulthood affect the corpus callosum differently . we hypothesized there would be greater microstructural changes of the callosal white matter in earlier injuries , due to the developmental trajectory of the corpus callosum . the degree of callosal involvement may help to explain the differences in motor deficits that exist between pediatric and adult hemiplegia . forty - one participants were recruited for this study into one of four groups : pediatric hemiplegia ( n  =  11 ) , pediatric control ( n  =  10 ) , adult hemiplegia ( n  =  10 ) , and adult control ( n  =  10 ) . the pediatric hemiplegia group consisted of children who sustained unilateral brain injuries before the age of ten years . the etiologies of this group were mixed and therefore represent the wide range of individuals clinically labeled as hemiplegic due to unilateral motor deficits . etiologies included intraventricular hemorrhage , internal capsule ischemic damage , middle cerebral artery infarct , intracranial bleeds , and arteriovenous malformations . the average age of the children in this group was 10.12    1.96  years , with six female and five male participants . eight of the children had clinical presentations of right hemiplegia ( due to left sided lesion ) , with the remaining three having left hemiplegia . within the pediatric hemiplegia group , five participants had prenatally acquired lesions ( late second to early third trimester ) , four had perinatally acquired lesions ( late third trimester to two months after birth ) , and two had postnatally acquired lesions ( 6  months to 10  years ) . the upper extremity fugl - meyer scores for the pediatric hemiplegia group ranged from 24 to 65 , with an average of 37.7    11.2 out of 66 possible points ( fasoli et al . , the gross motor functional classification system ( gmfcs ) classified all participants as either gmfcs level i ( n  =  6 ) or level ii ( n  =  5 ) ( rosenbaum et al . , 2008 ) . iii ( i : n  =  2 ; ii : n  =  7 ; iii : n  =  2 ) ( eliasson et al . , 2006 ) . the pediatric control group consisted of convenience sample of typically developing children with no history of neurological diagnoses . the average age of the pediatric control group was 12.3    3.89  years , with three female and seven male participants . there was no significant difference between the ages of the pediatric hemiplegia and pediatric control groups ( p  =  0.136 ) . the average age of the adult hemiplegia group was 59.1    11.6  years , and consisted of three females and seven male participants ; 8 with right sided hemiplegia and 2 with left sided hemiplegia . adult hemiplegia participants all had a single unilateral stroke at least one year prior to participation in the study with remaining upper extremity deficits . upper extremity fugl - meyer scores ranged from 12 to 40 , with an average of 19.9    9.0 out of 66 points . the adult control group consisted of a convenience sample of right - handed adults with no neurological history . anatomical mris depicting the lesion locations for both the pediatric hemiplegia and adult hemiplegia groups can be found in tables  1 and 2 . procedures were in accordance with institutional guidelines , and this study was approved by northwestern university 's institutional review board . all subjects underwent diffusion tensor imaging on a 3  t siemens tim trio scanner . an echo - planar based diffusion imaging sequence was used with diffusion weighting of 1000  s / mm in 60 different directions , as well as 8 scans without diffusion weighting . the scan parameters used were : tr  =  5  s ; te  =  85  ms , matrix  =  128    128 ; fov  =  256  mm , and 72 slices with thickness 2  mm . additionally , t1 weighted images were collected , using an mp - rage sequence with the following acquisition parameters : tr  =  2.3  s , te  =  3  ms , ti  =  900  ms , matrix  =  256    256 and fov  =  256    256  mm . a diffusion tensor model was fit at each voxel , from which voxelwise values for fractional anisotropy ( fa ) were calculated . for each participant , masks were hand - drawn on the corpus callosum at the midsagittal slice using a directional color map as a guide . the corpus callosum was sectioned anteriorly to posteriorly into five regions corresponding with the location of the cortical projections ( i : prefrontal cortex ; ii : pre - motor and supplementary motor areas ; iii : primary motor cortex ; iv : primary sensory cortex ; and v : parietal , occipital , and temporal regions ) as previously described ( hofer and frahm , 2006 ) . for each region , the average fa was calculated as a measure of white matter microstructure , with higher values indicating more coherent and intact white matter . fa for each region was compared between groups using one - way ancovas with age as a covariate . when significance was found between groups with the ancova , groups were compared post - hoc using fisher 's lsd t - tests to correct for multiple comparisons . to investigate the differential effect of injury timing , two - way ancovas were computed to find the interaction between age ( pediatric vs. adult ) and group ( hemiplegia vs. control ) , again using age as a covariate . in addition to examining white matter microstructure with fa , the cross - sectional areas of each region were also calculated and statistically compared in the same manner to detect thinning of the corpus callosum . to evaluate if age could contribute to differences in fa or cross - sectional area in the pediatric participants , correlations were completed for the pediatric control group between age and the fa and area results for each region . a subset of the pediatric hemiplegia ( n  =  6 , age range 7.711.6  yrs , average 9.67    1.34  yrs ) and pediatric control ( n  =  3 , age range 7.814.4  yrs , average 11.0    3.30  yrs ) groups underwent a quantitative assessment of mirror movements . detailed methods for this portion of the study were previously published ( sukal - moulton et al . , 2013 ) . in brief , isokinetic efforts were completed by the non - paretic arm at 100 , 50 , and 25% of maximal voluntary elbow flexion torques with instruction to relax the paretic upper limb . the involuntary elbow flexion torques generated by the paretic arm were measured by a six degree - of - freedom load cell and normalized as percentage of maximum elbow flexion torque of the paretic upper limb . correlations were also calculated for the fa and volume of each region with the amplitude of involuntary torque measured . statistical analysis was completed using spss ( version 21 , spss , inc . ) , with a p value  <  0.05 considered to be statistically significant for all tests . 1 . significant differences in fa between groups were found for all regions of the corpus callosum except for the prefrontal region ( i : f  =  1.623 , p  =  0.201 ; ii : f  =  5.087 , p  =  0.005 ; iii : f  =  7.423 , p  =  0.001 ; iv : f  =  5.200 , p  =  0.004 ; v : f  =  5.442 , p  =  0.003 ) , as shown in fig .  2 . pediatric control subjects and pediatric hemiplegia subjects differed significantly for regions ii ( p  =  0.049 ) , iv ( p  =  0.036 ) , and v ( p  =  0.025 ) . comparisons between adult control subjects and adult hemiplegia subjects were different for region v only ( p  =  0.027 ) . the interaction effect between age ( pediatric vs. adult ) and group ( hemiplegia vs. control ) was significant for region v ( f  =  8.804 , p  =  0.005 ) . age was not found to correlate with fa values in any region for the pediatric control group . as observed in fig .  1 , the corpus callosum appears thinner in the individual with pediatric hemiplegia compared to both the adult with hemiplegia and the control subject . significant differences were found for all regions ( i : f  =  6.090 , p  =  0.002 ; ii : f  =  3.949 , p  =  0.016 ; iii : f  =  13.333 , p  <  0.001 ; iv : f  =  7.616 , p  <  0.001 ; v : f  =  10.659 , p  <  0.001 ) . comparisons between cross - sectional area in pediatric control and pediatric hemiplegia subjects were significant for all regions ( i : p  =  0.007 ; ii : 0.017 ; iii : p  <  0.001 ; iv : p  =  0.027 ; v : p  =  0.001 ) . comparisons between adult control and adult hemiplegia patients were only significant for region iv ( p  =  0.012 ) . significant interactions between age ( pediatric vs. adult ) and group ( control vs. hemiplegia ) were found for regions iii v ( iii : f  =  13.162 , p  =  0.001 ; iv : f  =  12.657 , p  =  0.001 ; v : f  =  6.422 , p  =  0.016 ) . age was not found to have a significant correlation with cross - sectional area in any region for the pediatric control participants . the pediatric hemiplegia group did exhibit greater levels of involuntary interlimb coupling in their paretic elbow when the non - paretic elbow was engaged in a task , as shown in fig . this was true for all levels of torque generated with the non - paretic elbow . when correlating the torques in the paretic elbow with the dti results , significant correlations were found for the volume of region iii with the torque in the 100% condition ( p  =  0.046 , pearson coefficient  =    0.741 ) and between volume of region ii with the torque in the 50% condition ( p  =  0.021 , pearson coefficient  =    0.827 ) . losses in transcallosal motor pathways following unilateral brain injuries can contribute to deficits with bimanual coordination , complex unilateral tasks , and locomotion . based on our results , the corpus callosum is affected to a greater extent by unilateral injuries occurring early in life compared to adult - onset stroke . this was found both in terms of white matter microstructural properties ( fa ) and size ( cross - sectional area ) of the corpus callosum . differences between pediatric and adult hemiplegia may be due to the developmental state of the corpus callosum at the time of injury , as well as subsequent reorganization . myelination of the corpus callosum begins in the splenium at 13  months , followed by the body , and lastly the genu at 6  months ( deoni et al . 2001 ) . continued maturation is associated with increased interhemispheric inhibition and decreasing mirror movements , which typically vanish by age 8 for simple unimanual tasks ( koerte et al . , 2009 ) . to determine if there was any effect of age on the fa values we observed , we correlated age and fa for each region for the pediatric control group . this was to be expected , as our cohort had an average age of 12  years old , and thus large age - related changes in the corpus callosum would no longer be expected . based on the developmental trajectory of the corpus callosum , injuries early in life are likely to affect the developmental course of the immature callosal fibers . additionally , with early injuries , especially when occurring prenatally , both motor areas may reorganize to the intact hemisphere , thus negating the need for callosal communication between motor areas ( carr , 1996 ; eyre et al . our findings that the pediatric hemiplegia group compared to pediatric control subjects had reduced cross - sectional area of the corpus callosum across all regions , as well as reduced fractional anisotropy values in three of the five callosal regions , illustrate how greatly the corpus callosum can be affected by early unilateral injury . reductions in transcallosal motor fibers would contribute to decreased interhemispheric inhibition between the two primary motor areas , and thus a greater occurrence of mirror movements in this population . the effect of a unilateral brain injury on the corpus callosum was less widespread in the adult hemiplegia group compared with the pediatric hemiplegia group . in adult hemiplegia , only the primary sensory ( region iv ) cortical connections demonstrated a change in cross - sectional area , and significant differences in fractional anisotropy were only observed in the region corresponding to parietal , occipital , and temporal cortical areas ( region v ) . this supports previous findings that callosal fibers connecting higher order motor areas are affected following stroke . while previous studies have reported other regions of the corpus callosum being affected as well ( gupta et al . , 2006 ; wang et al . , 2011 ) , the subjects used in this current study represented a more chronic stroke population , where more recovery and normalization of activity may have occurred . in comparing the differential effect of age on callosal changes , the pediatric hemiplegia group had greater microstructural changes ( decreased fa ) in the callosal region connecting the temporal , parietal , and occipital areas . the temporoparietal junction has been implicated in predictive motor coding , with losses of connectivity postulated to affect motor performance ( wang et al . , 2011 ) . this region also demonstrated reduced area , along with the regions corresponding to primary motor and primary sensory connections . therefore we can conclude that unilateral lesions occurring early in life have a greater effect on the corpus callosum than injuries occurring in adulthood , both in terms of the size of corpus callosum and the microstructural properties of the white matter . in additional to maturational differences accounting for the greater losses in callosal fibers in pediatric hemiplegia compared to adult hemiplegia , the nature of the lesions while both populations had unilateral brain injuries , periventricular lesions are more typical in pediatric populations , thus there may be a greater impact on the corpus callosum directly from the lesion . however , the extent of the damage to the corpus callosum can only be truly appreciated using dti methods , as done in this paper , and therefore the full extent of callosal damage is commonly missed with clinical studies . of note is that based on upper extremity fugl - meyer scores , the adult hemiplegia group is more impaired than the pediatric hemiplegia group . this can be explained by the limitations of the fugl - meyer scale , which focuses mainly on abnormal synergy patterns . while these patterns are characteristic in adult hemiplegia , they may not be the underlying movement impairment in the majority of children with hemiplegia . in the pediatric condition , especially with pre- and perinatally acquired injuries , it is likely that the loss of independent limb control is more affected ( sukal - moulton et al . , 2013 ) . as the results of this study show , pediatric hemiplegia implicates the corpus callosum more than in adult hemiplegia , the effects of which are not specifically measured by the fugl - meyer assessment . the results from the subset of individuals that underwent the bilateral torque experiment clearly show that the pediatric hemiplegia group exhibits mirror movements while the control group does not . while only two regions demonstrated significant correlations , this may be due to a limited sample size . interestingly , it was area and not fractional anisotropy that was found to be correlated . this study offers insight into the differences in clinical presentation between children and adults following unilateral brain injuries . the reduced size and microstructural changes ( as shown by fractional anisotropy ) in the corpus callosum in pediatric hemiplegia compared to adult hemiplegia and control subjects supports the observation that losses of independent limb control is a greater problem in the pediatric population . this finding gives neuroanatomical support for the need for unique interventions for pediatric and adult stroke . future work will further divide the pediatric hemiplegia group based on pre , peri , or postnatally acquired unilateral brain injuries to further explore the influence of injury timing on callosal microstructure and associated movement dysfunctions . julius pa dewald and national science foundation graduate research fellowship to dr . rachel l. hawe .
motor impairments following unilateral brain injuries may be related to changes in the corpus callosum . 
 the purpose of this study was to determine if the corpus callosum is impacted differently in pediatric versus adult hemiplegia . 
 diffusion tensor imaging was completed on 41 participants ( 11 pediatric hemiplegia , 10 adult hemiplegia , 10 pediatric control and 10 adult control ) . 
 fractional anisotropy values and cross - sectional areas for five regions of the corpus callosum were compared between subject groups . 
 additionally , the amount of involuntary activity in the paretic elbow was quantified during non - paretic elbow flexion tasks for a subset of pediatric hemiplegia participants . 
 fractional anisotropy values were reduced in pediatric hemiplegia compared to pediatric control subjects in callosal regions corresponding to premotor and supplementary motor areas , primary sensory cortex , and parietal , temporal , and occipital cortices . 
 differences in fractional anisotropy between adult stroke and adult controls were only found in the region corresponding to parietal , temporal , and occipital cortices . 
 cross - sectional area was affected in all regions of the corpus callosum in pediatric hemiplegia , but only in the primary sensory region in adult hemiplegia . 
 additionally , changes in the cross - sectional areas were correlated with involuntary mirror movements in the pediatric hemiplegia group . in conclusion , 
 the corpus callosum is affected to a greater extent in pediatric compared to adult hemiplegia , which may explain why unsuppressed mirror movements and difficulty with bimanual coordination are greater problems in this population .