Contralateral Corticospinal Tract Research Articles

A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.

Significance of Corticospinal, Associative and Inter-Hemispheric Tracts for the Development of Posttraumatic Hemiparesis

Motor disorders are among the most common consequences of severe craniocerebral injury (traumatic brain injury — TBI). Deeper insights into pathophysiological mechanisms of these disorders is important both from a theoretical point of view and in terms of improving neurorehabilitation approaches.The aim of the study was to investigate the correlation of right–sided posttraumatic hemiparesis severity with composite characteristics of fractional anisotropy (FA) in the segments of the corpus callosum (CC), corticospinal tract (CST) and the inferior fronto-occipital fasciculus (IFO) at different stages of traumatic disease (acute, subacute and long-term periods).Material and methods. Cases of 43 patients with TBI were analyzed (28 men and 15 women aged 13 to 59 years, mean age 28±9 years). Forty patients were diagnosed with severe TBI with diffuse axonal damage, three patients had moderate severity TBI. Long-term follow up included continuous clinical and neurological examination with evaluation of patient’s level of consciousness using the CRS-R scale, and the degree of motor deficits in right-sided hemiparesis using a five-point scale. During three post-TBI periods (up to 1 month, from 1 to 6 months, and from 6 to 12 months), patients were examined using diffusion tensor MRI (DTI), tractography and FA. Motor, cortico-spinal tracts and IFO were divided by measurement grid, correlations between FA and scores of right-sided hemiparesis were calculated for each segment.Results. FA correlations (P0.05) with the severity of hemiparesis were established not only for CST motor-specific segments, but also for some CC and IFO segments. In the early period of TBI significant correlations with hemiparesis severity were found not only in the contralateral CST segments, but also in the ipsilateral ones. Significant differences in FA in the related CC and CST segments were found between the groups with good and limited motor recovery: at all stages after TBI, FA was higher in patients with successful recovery.Conclusion. The results of the study provide better insight into pathophysiological mechanisms of post-traumatic motor disorders development, therefore favoring optimization of therapeutic strategies.

Multiparametric mapping of white matter reorganizations in patients with frontal glioma-related epilepsy.

Epilepsy is a common symptom in diffuse lower-grade glioma (DLGG). The specific role of white matter (WM) alteration in patients with glioma-related epilepsy (GRE) is largely unknown. This study aims to investigate the reorganization of WM tracts and changes in structural networks related to GRE. Diffusion-weighted images were collected from 70 patients with left frontal DLGG (GRE = 33, non-GRE = 37) and 41 healthy controls (HC). Tractometry with TractSeg was applied to segment tracts and quantify fractional anisotropy (FA) along each tract. Structural network was constructed using constrained spherical deconvolution and probabilistic tractography. FA and network properties were compared among three groups. Compared with HC, both GRE and non-GRE showed decreased FA in contralateral inferior fronto-occipital fasciculus, superior longitudinal fasciculus II and arcuate fasciculus, increased nodal efficiency in contralateral nodes of frontal-parietal and limbic networks, whereas decreased degree centrality and betweenness centrality in nodes of dorsal temporal lobe and rostral middle frontal gyrus (rMFG). Additionally, when compared GRE with non-GRE, increased FA in contralateral corticospinal tract (CST) and lower betweenness centrality in paracentral lobule (PCL) in GRE (all p < 0.05 after Bonferroni correction). This study indicates that patients with left frontal DLGG exhibit complex WM reorganization, and the altered regions mainly concentrated in the language, frontal-parietal and limbic networks. Moreover, the preserved integrity in contralateral CST and server decreased nodal betweenness in PCL may be potential neuroimaging markers underlying the occurrence of presurgical seizures of GRE.

Unilateral perirolandic polymicrogyria with ipsilateral brainstem hypoplasia and compensatory contralateral hyperplasia.

Polymicrogyria (PMG) is a malformation of cortical development that occurs mostly in the perisylvian region bilaterally (60-70%), most often presenting with epilepsy. Unilateral cases are much rarer with hemiparesis being the predominant symptom. We report a case of a 71-year-old man with right perirolandic PMG with ipsilateral hypoplasia and contralateral hyperplasia of the brainstem, with only non-progressive left-sided mild spastic hemiparesis. This imaging pattern is thought to occur due to the normal process of withdrawal of the axons of the corticospinal tract (CST) connected to aberrant cortex, possibly with compensatory contralateral CST hyperplasia. However, the majority of cases is additionally present with epilepsy. We believe it is worthwhile to investigate imaging patterns of PMG with symptoms' correlation, particularly with the help of techniques such as advanced brain imaging to assist in the study of cortical development along with adaptive somatotopic organization of the cerebral cortex in MCD with possible clinical applications.

Not a benign motor neuron disease: longitudinal imaging captures relentless motor connectome disintegration in primary lateral sclerosis.

Primary lateral sclerosis (PLS) is a progressive upper motor neuron disorder associated with considerable clinical disability. Symptoms are typically exclusively linked to primary motor cortex degeneration and the contribution of pre-motor, supplementary motor, cortico-medullary and inter-hemispheric connectivity alterations are less well characterized. In a single-centre, prospective, longitudinal neuroimaging study 41 patients with PLS were investigated. Patients underwent standardized neuroimaging, genetic profiling with whole exome sequencing, and comprehensive clinical assessments including upper motor neuron scores, tapping rates, mirror movements, spasticity assessment, cognitive screening and evaluation for pseudobulbar affect. Longitudinal neuroimaging data from 108 healthy controls were used for image interpretation. A standardized imaging protocol was implemented including 3D T1-weighted structural, diffusion tensor imaging and resting-state functional magnetic resonance imaging. Following somatotopic segmentation, cortical thickness analyses, probabilistic tractography, blood oxygenation level dependent signal analyses and brainstem volumetry were conducted to evaluate cortical, brainstem, cortico-medullary and inter-hemispheric connectivity alterations both cross-sectionally and longitudinally. Our data confirm progressive primary motor cortex degeneration, considerable supplementary motor and pre-motor area involvement, progressive brainstem atrophy, cortico-medullary and inter-hemispheric disconnection, and close associations between clinical upper motor neuron scores and somatotopic connectivity indices in PLS. Primary lateral sclerosis is associated with relentlessly progressive motor connectome degeneration. Clinical disability in PLS is likely to stem from a combination of intra- and inter-hemispheric connectivity decline and primary, pre- and supplementary motor cortex degeneration. Simple 'bedside' clinical tools, such as tapping rates, are excellent proxies of the integrity of the relevant fibres of the contralateral corticospinal tract.

Progress of researches on involvement of corticospinal tract in the effect of acupuncture on improvement of post-stroke motor dysfunction

The corticospinal tract (CST), descending from the frontoparietal cortex and traveling down to terminate at the anterior horn of the spinal cord to mediate voluntary movements, is frequently injured from the infarcted or hemorrhagic cerebrovascular insults due to stroke. Under the circumstances, motor dysfunction seriously affects the patient's quality of life. Acupuncture therapy has a sequelae, especially in improving motor deficits. In the present paper, we reviewed the current development of researches on acupuncture treatment of poststroke motor dysfunction and its biological mechanisms from 1) delaying patients' development of neuronal degeneration and white matter fibrosis (Wallerian degeneration), 2) improving patients' upper limb motor function and daily life ability by promoting the repair of white matter tracts and CST on the affected side, 3) promoting the compensation of CST on the healthy side, 4) reconstructing the motor conduction pathway to strengthen the bilateral brain connection in ex-perimental animals, and 5) strengthening the sprouting of the contralateral CST to dominate the affected side again across the midline. In addition, acupuncture stimulation induced improvement of axonal rewiring for corticospinal innervation is also possibly related to its functions in accelerating the synthesis and release of neurotrophic factors, down-regulating Nogo-A/RhoA signaling and activating vascular epithelial growth factor/Dll4/Notch signaling pathways.

Impaired corticospinal tract in chronic ankle instability: A diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) study at 7.0 Tesla

ObjectivesElectrophysiological studies have revealed that abnormal function of the corticospinal pathway might contribute to chronic ankle instability, but structural evidence underlying the abnormality is lacking. The purpose of this study was to quantitate microstructural differences between corticospinal tracts in patients with chronic ankle instability and healthy controls. DesignCross-sectional. MethodsSeventeen patients with chronic ankle instability and sixteen healthy controls underwent diffusion weighted-imaging scans using an ultra-high-field 7.0 Tesla magnetic resonance imaging scanner. We focused on corticospinal tracts as a region of interest and performed classical diffusion tensor imaging and the advanced neurite orientation dispersion and density imaging outcomes that measured the microstructure of white matter tracts. Correlation analyses were also performed between the significantly different diffusion outcomes in both groups. ResultsThe patients with chronic ankle instability showed significantly lower fractional anisotropy (p-corrected = 0.045) and higher orientation dispersion index (p-corrected = 0.033) when compared with healthy controls. These two measures were significantly correlated in the healthy controls (r = −0.56, p = 0.024) and the CAI patient group (r = −0.53, p = 0.029). ConclusionsThis study revealed that the contralateral corticospinal tract of the unstable ankle in patients with chronic ankle instability exhibited impaired integrity, which was associated with abnormally organized neurites. We propose that this is a useful target for the clinical assessment of chronic ankle instability and the development of targeted neuromuscular rehabilitation.

Effect of the long-term lack of half visual inputs on the white matter microstructure in congenital monocular blindness

Individuals with congenital monocular blindness are born without binocular vision and stereopsis, the effects of which on the brain microstructure are largely unknown. This study aims to investigate the microstructural characteristics of white matter tracts over the whole brain in congenital monocular blindness. We used T1-weighted MRI and diffusion tensor imaging (DTI) to investigate the microstructural characteristics of the brain in 16 patients with unilateral congenital microphthalmia (CM) and 16 matched normally sighted controls. The DTI-derived metrics were assessed using atlas-level analysis with FDR correction and TBSS-level analysis with threshold-free cluster enhancement correction (TFCE). CM exhibited significantly abnormal DTI-derived indices (p < 0.05, q < 0.05 of FDR correction) as follows: 1) declined fractional anisotropy (FA) in the inferior fronto-occipital fasciculus contralateral to the affected eye, bilateral inferior longitudinal fasciculus, while enhanced in the ipsilateral cingulum; 2) increased local diffusion homogeneity in the contralateral corticospinal tract while decreased in the ipsilateral superior longitudinal fasciculus; 3) reduced axial diffusivity (AD) in the body of corpus callosum. Meanwhile, the alteration tendencies of FA, AD, and radial diffusivity (RD) in the forceps major (increased FA and AD, decreased RD) and forceps minor (decreased FA and AD, increased RD) were interestingly opposite. These results reveal extensive microstructural abnormalities of WM ranging from sensory modalities to other cross-modal pathways involving language, execution, memory, emotion, fine movement, and interhemispheric communication as well. This study provides novel evidence of large-scale subcortical involvement subsequent to prolonged loss of half visual inputs, which may be associated with developmental delay and compensatory plasticity.

Improvements in Upper Extremity Function Following Intensive Training Are Independent of Corticospinal Tract Organization in Children With Unilateral Spastic Cerebral Palsy: A Clinical Randomized Trial.

Background/Objectives: Intensive training of the more affected upper extremity (UE) has been shown to be effective for children with unilateral spastic cerebral palsy (USCP). Two types of UE training have been particularly successful: Constraint-Induced Movement Therapy (CIMT) and Bimanual training. Reorganization of the corticospinal tract (CST) early during development often occurs in USCP. Prior studies have suggested that children with an ipsilateral CST controlling the affected UE may improve less following CIMT than children with a contralateral CST. We tested the hypothesis that improvements in UE function after intensive training depend on CST laterality.Study Participants and Setting: Eighty-two children with USCP, age 5 years 10 months to 17 years, University laboratory setting.Materials/Methods: Single-pulse transcranial magnetic stimulation (TMS) was used to determine each child's CST connectivity pattern. Children were stratified by age, sex, baseline hand function and CST connectivity pattern, and randomized to receive either CIMT or Bimanual training, each of which were provided in a day-camp setting (90 h). Hand function was tested before, immediately and 6 months after the intervention with the Jebsen-Taylor Test of Hand Function, the Assisting Hand Assessment, the Box and Block Test, and ABILHAND-Kids. The Canadian Occupational Performance Measure was used to track goal achievement and the Pediatric Evaluation of Disability Inventory was used to assess functioning in daily living activities at home.Results: In contrast to our hypothesis, participants had statistically similar improvements for both CIMT and Bimanual training for all measures independent of their CST connectivity pattern (contralateral, ipsilateral, or bilateral) (p < 0.05 in all cases).Conclusions/Significance: The efficacy of CIMT and Bimanual training is independent of CST connectivity pattern. Children with an ipsilateral CST, previously thought to be maladaptive, have the capacity to improve as well as children with a contralateral or bilateral CST following intensive CIMT or Bimanual training.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02918890.

Functional connectivity and upper limb function in patients after pediatric arterial ischemic stroke with contralateral corticospinal tract wiring

To develop individualized motor rehabilitation, knowledge of the relationship between neuroplastic reorganization and motor recovery after pediatric arterial ischemic stroke (AIS) is crucial. Thus, we investigated functional connectivity in patients after AIS with good motor outcome and in patients with hemiparesis compared with typically developing peers. We included 18 patients (n = 9 with hemiparesis, n = 9 with good motor outcome) with pediatric AIS in the chronic phase (≥ 2 years after diagnosis, diagnosed > 16 years) and 18 peers matched by age and gender. Participants underwent a standardized motor assessment, single-pulse transcranial magnetic stimulation to determine the type of corticospinal tract wiring, and resting-state functional magnetic resonance imaging to examine motor network connectivity. Corticospinal tract wiring was contralateral in all participants. Patients with hemiparesis had lower interhemispheric connectivity strength compared with patients with good clinical outcome and peers. Patients with good clinical outcome had higher intrahemispheric connectivity strength compared with peers. Further, higher intrahemispheric connectivity was related to better motor outcome in patients. Our findings suggest that better motor outcome after pediatric AIS is related to higher motor network connectivity strength. Thus, resting-state functional connectivity might be predictive for motor recovery after pediatric AIS.

Peri-hematoma corticospinal tract integrity in intracerebral hemorrhage patients: A diffusion-tensor imaging study

BackgroundThe impact of perihematoma edema in Intracerebral Hemorrhage (ICH) on white matter integrity is uncertain. Fractional Anisotropy (FA), as measured with Diffusion Tensor Imaging (DTI), can be used to assess white matter microstructure. We tested the hypotheses that sections of the Corticospinal Tract (CST) passing through perihematoma edema would 1) have low FA relative to the contralateral CST and 2) would predict NIHSS motor score in ICH patients. MethodsPatients were prospectively imaged with DTI at 48 h and 7 days after onset. Edema volume/extent was measured on CT at baseline and 24 h. FA, mean, axial and radial diffusivity were measured in the perihematoma edema, contralateral CST and sections of CST passing through the edema (‘edematous CST’). ResultsPatients (n = 27, mean age 67 ± 13) were scanned with DTI at a median (IQR) of 42.3 (24.5) hours and 7.7 (1.8) days from onset. Median acute ICH volume was 8.8 (22) ml. FA in edematous CST at 72 h was decreased (0.37 ± 0.03) relative to contralateral CST (0.52 ± 0.06; p < 0.0001). Day 7 FA in edematous CST (0.35 ± 0.08) was also decreased compared to contralateral CST (0.54 ± 0.06; p < 0.0001). FA remained stable between 72 h (0.37 ± 0.03) and day 7 (0.35 ± 0.07; p = 0.350). FA at 72 h (ρ = −0.22, p = 0.420) and day 7 (ρ = −0.14, p = 0.624) was unrelated to 90-day motor score. ConclusionsFA is decreased in the CST where it passes through the edema. Decreased FA in the edematous CST remained stable over time, was unrelated to motor score, and may represent water infiltration into the tracts rather than axonal injury.

Manual dexterity in late childhood is associated with maturation of the corticospinal tract

PurposeDespite the important role of manual dexterity in child development, the neurobiological mechanisms associated with manual dexterity in childhood remain unclear. We leveraged fixel-based analysis (FBA) to examine the longitudinal association between manual dexterity and the development of white matter structural properties in the corticospinal tract (CST). MethodsHigh angular diffusion weighted imaging (HARDI) data were acquired for 44 right-handed typically developing children (22 female) aged 9-13 across two timepoints (timepoint 1: mean age 10.5 years ± 0.5 years, timepoint 2: 11.8 ± 0.5 years). Manual dexterity was assessed using the Grooved Pegboard Test, a widely used measure of manual dexterity. FBA-derived measures of fiber density and morphology were generated for the CST at each timepoint. Connectivity-based fixel enhancement and mixed linear modelling were used to examine the longitudinal association between manual dexterity and white matter structural properties of the CST. ResultsLongitudinal mixed effects models showed that greater manual dexterity of the dominant hand was associated with increased fiber cross-section in the contralateral CST. Analyses further demonstrated that the rate of improvement in manual dexterity was associated with the rate of increase in fiber cross-section in the contralateral CST between the two timepoints. ConclusionOur longitudinal data suggest that the development of manual dexterity in late childhood is associated with maturation of the CST. These findings significantly enhance our understanding of the neurobiological systems that subserve fine motor development and provide an important step toward mapping normative trajectories of fine motor function against microstructural and morphological development in childhood.

Utility of a Quantitative Approach Using Diffusion Tensor Imaging for Prognostication Regarding Motor and Functional Outcomes in Patients With Surgically Resected Deep Intracranial Cavernous Malformations.

Resection of deep intracranial cavernous malformations (CMs) is associated with a higher risk of neurological deterioration and uncertainty regarding clinical outcomes. To examine diffusion tractography imaging (DTI) data evaluating the corticospinal tract (CST) in relation to motor and functional outcomes in patients with surgically resected deep CMs. Perilesional CST was characterized as disrupted, displaced, or normal. Mean fractional anisotropy (FA) values were obtained for whole ipsilateral CST and in 3 regions: subcortical (proximal), perilesional, and distally. Mean FA values in anatomically equivalent regions in the contralateral CST were obtained. Clinical and radiological data were collected independently. Multivariable regression analysis was used for statistical analysis. A total of 18 patients [brainstem (15) and thalamus/basal ganglia (3); median follow-up: 270 d] were identified over 2 yr. The CST was identified preoperatively as disrupted (6), displaced (8), and normal (4). Five of 6 patients with disruption had weakness. Higher preoperative mean FA values for distal ipsilateral CST segment were associated with better preoperative lower (P<.001), upper limb (P=.004), postoperative lower (P=.005), and upper limb (P<.001) motor examination. Preoperative mean FA values for distal ipsilateral CST segment (P=.001) and contralateral perilesional CST segment (P<.001) were negatively associated with postoperative modified Rankin scale scores. Lower preoperative mean FA values for overall and defined CST segments corresponded to worse patient pre- and postoperative motor examination and/or functional status. FA value for the distal ipsilateral CST segment has prognostic potential with respect to clinical outcomes.

Limited capacity for ipsilateral secondary motor areas to support hand function post-stroke.

Ipsilateral-projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke-induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening. Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post-stroke, although with no apparent capacity to support hand function.

White matter characteristics of motor, sensory and interhemispheric tracts underlying impaired upper limb function in children with unilateral cerebral palsy.

This study explored the role of lesion timing (periventricular white matter versus cortical and deep grey matter lesions) and type of corticospinal tract (CST) wiring pattern (contralateral, bilateral, ipsilateral) on white matter characteristics of the CST, medial lemniscus, superior thalamic radiations and sensorimotor transcallosal fibers in children with unilateral cerebral palsy (CP), and examined theassociation with upper limb function. Thirty-four children (mean age 10 years 7 months ± 2 years 3 months) with unilateral CP underwent a comprehensive upper limb evaluation and diffusion weighted imaging (75 directions, b value 2800). Streamline count, fractional anisotropy and mean diffusivity were extracted from the targeted tracts and asymmetry indices were additionally calculated. Transcranial magnetic stimulation was applied to assess the CST wiring pattern. Results showed a more damaged CST in children with cortical and deep grey matter lesions (N = 10) and ipsilateral CST projections (N = 11) compared to children with periventricular white matter lesions (N = 24; p < 0.02) and contralateral CST projections (N = 9; p < 0.025), respectively. Moderate to high correlations were found between diffusion metrics of the targeted tracts and upper limb function (r = 0.45-0.72; p < 0.01). Asymmetry indices of the CST and sensory tracts could best explain bimanual performance (74%, p < 0.0001) and unimanual capacity (50%, p = 0.004). Adding lesion timing and CST wiring pattern did not further improve the model of bimanual performance, while for unimanual capacity lesion timing was additionally retained (58%, p = 0.0002). These results contribute to a better understanding of the underlying neuropathology of upper limb function in children with unilateral CP and point towards a clinical potential of tractography.

PKC\u03b3 promotes axonal remodeling in the cortico-spinal tract via GSK3\u03b2/\u03b2-catenin signaling after traumatic brain injury

Traumatic brain injury (TBI) is a common cause of death and disability. Enhancing the midline-crossing of the contralateral corticospinal tract (CST) to the denervated side of spinal cord facilitates functional recovery after TBI. Activation of the gamma isoform of PKC (PKCγ) in contralateral CST implicates its roles in promoting CST remodeling after TBI. In this study, we deployed loss and gain of function strategies in N2a cells and primary cortical neurons in vitro, and demonstrated that PKCγ is not only important but necessary for neuronal differentiation, neurite outgrowth and axonal branching but not for axonal extension. Mechanically, through the phosphorylation of GSK3β, PKCγ stabilizes the expression of cytosolic β-catenin and increase GAP43 expression, thus promoting axonal outgrowth. Further, rAAV2/9-mediated delivery of constitutive PKCγ in the corticospinal tract after unilateral TBI in vivo additionally showed that specifically delivery of active PKCγ mutant to cortical neuron promotes midline crossing of corticospinal fibers from the uninjured side to the denervated cervical spinal cord. This PKCγ-mediated injury response promoted sensorimotor functional recovery. In conclusion, PKCγ mediates stability of β-catenin through the phosphorylation of GSK3β to facilitate neuronal differentiation, neurite outgrowth and axonal branching, and PKCγ maybe a novel therapeutic target for physiological and functional recovery after TBI.

Influence of the corticospinal tract wiring pattern on sensorimotor functional connectivity and clinical correlates of upper limb function in unilateral cerebral palsy

In children with unilateral cerebral palsy (uCP), the corticospinal tract (CST)-wiring patterns may differ (contralateral, ipsilateral or bilateral), partially determining motor deficits. However, the impact of such CST-wiring on functional connectivity remains unknown. Here, we explored resting-state sensorimotor functional connectivity in 26 uCP with periventricular white matter lesions (mean age (standard deviation): 12.87 m (±4.5), CST wiring: 9 contralateral, 9 ipsilateral, 6 bilateral) compared to 60 healthy controls (mean age (standard deviation): 14.54 (±4.8)), and between CST-wiring patterns. Functional connectivity from each M1 to three bilateral sensorimotor regions of interest (primary sensory cortex, dorsal and ventral premotor cortex) and the supplementary motor area was compared between groups (controls vs. uCP; and controls vs. each CST-wiring group). Seed-to-voxel analyses from bilateral M1 were compared between groups. Additionally, relations with upper limb motor deficits were explored. Aberrant sensorimotor functional connectivity seemed to be CST-dependent rather than specific from all the uCP population: in the dominant hemisphere, the contralateral CST group showed increased connectivity between M1 and premotor cortices, whereas the bilateral CST group showed higher connectivity between M1 and somatosensory association areas. These results suggest that functional connectivity of the sensorimotor network is CST-wiring-dependent, although the impact on upper limb function remains unclear.

The effect of walnut rolling training on hand function and corticospinal tract.

We investigated the effect of the walnut rolling training for two weeks on the hand function and corticospinal tract (CST) in normal subjects. Seventeen right-handed normal subjects performed walnut rolling training with their non-dominant (left) hand, with the right hand defined as the control side. The walnut rolling training was performed three times daily, for 30 minutes at a time, over two weeks. The Purdue Pegboard Test (PPT), tip pinch and grip strength (GS) were used evaluate the change of hand function, and diffusion tensor tractography (DTT) evaluated change of the CST and transcallosal fibers for the hand motor somatotopy. All of the clinical scores in terms of PPT, tip pinch and GS increased significantly in the post-training (PPT: 16.59±1.09, tip pinch: 5.03±2.18, GS: 40.61±10.99) in the left hand compared with pre-training (PPT: 14.94±1.36, tip pinch: 3.66±1.44, GS: 33.58±11.08) (P<0.05). By contrast, the clinical scores for the right hand did not differ significantly between pre- (PPT: 16.25±1.98, tip pinch: 5.75±2.26, GS: 37.58±14.61) and post-training (PPT: 16.97±1.67, tip pinch: 5.66±2.31, GS: 37.82±14.25). The fiber numbers (FN) of the right CST increased significantly in post-training DTT (2,123.05±529.07) compared with pre-training DTT (1,734.73±581.84) (P<0.05), whereas fractional anisotropy (FA) (pre-training: 0.50±0.02, post-training: 0.51±0.01) did not change significantly. Neither FA nor FN of the left CST and transcallosal fibers changed significantly from pre- (FA: 0.44±0.02, FN: 1,871.15±636.36) to post-training DTTs (FA: 0.45±0.03, FN: 1,823.84±701.14). We demonstrated improvement of hand function and facilitation of the contralateral CST by walnut rolling training in normal subjects. Our results suggest that walnut rolling training can be used for improvement of hand function and facilitation of the contralateral CST.

The value of diffusion tensor tractography delineating corticospinal tract in glioma in rat: validation via correlation histology.

BackgroundAn assessment of the degree of white matter tract injury is important in neurosurgical planning for patients with gliomas. The main objective of this study was to assess the injury grade of the corticospinal tract (CST) in rats with glioma using diffusion tensor imaging (DTI).MethodsA total 17 rats underwent 7.0T MRI on day 10 after tumor implantation. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were acquired in the tumor, peritumoral and contralateral areas, and the ADC ratio (ipsilateral ADC/contralateral ADC) and rFA (relative FA = ipsilateral FA/contralateral FA) in the peritumoral areas were measured. The CST injury was divided into three grades and delineated by diffusion tensor tractography reconstruction imaging. The fiber density index (FDi) of the ipsilateral and contralateral CST and rFDi (relative FDi = ipsilateral FDi/contralateral FDi) in the peritumoral areas were measured. After the mice were sacrificed, the invasion of glioma cells and fraction of proliferating cells were observed by hematoxylin-eosin and Ki67 staining in the tumor and peritumoral areas. The correlations among the pathology results, CST injury grade and DTI parameter values were calculated using a Spearman correlation analysis. One-way analysis of variance was performed to compare the different CST injury grade by the rFA, rFDi and ADC ratio values.ResultsThe tumor cells and proliferation index were positively correlated with the CST injury grade (r = 0.8857, 0.9233, P < 0.001). A negative correlation was demonstrated between the tumor cells and the rFA and rFDi values in the peritumoral areas (r = −0.8571, −0.5588), and the proliferation index was negatively correlated with the rFA and rFDi values (r = −0.8571, −0.5588), while the ADC ratio was not correlated with the tumor cells or proliferation index. The rFA values between the CST injury grades (1 and 3, 2 and 3) and the rFDi values in grades 1 and 3 significantly differed (P < 0.05).ConclusionsDiffusion tensor imaging may be used to quantify the injury degrees of CST involving brain glioma in rats. Our data suggest that these quantitative parameters may be used to enhance the efficiency of delineating the relationship between fiber tracts and malignant tumor.

Whole Brain White Matter Microstructure and Upper Limb Function: Longitudinal Changes in Fractional Anisotropy and Axial Diffusivity in Post-Stroke Patients.

Background:Diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) measuring fractional anisotropy (FA) and axial diffusivity (AD) may be a useful biomarker for monitoring changes in white matter after stroke, but its associations with upper-limb motor recovery have not been well studied. We aim to describe changes in the whole-brain FA and AD in five post-stroke patients in relation to kinematic measures of elbow flexion to better understand the relationship between FA and AD changes and clinico-kinematic measures of upper limb motor recovery.Methods:We performed DTI MRI at two timepoints during the acute phase of stroke, measuring FA and AD across 48 different white matter tract regions in the brains of five hemiparetic patients with infarcts in the cortex, pons, basal ganglia, thalamus, and corona radiata. We tracked the progress of these patients using clinical Fugl-Meyer Assessments and kinematic measures of elbow flexion at the acute phase within 14 (mean: 9.4 ± 2.49) days of stroke symptom onset and at a follow-up appointment 2 weeks later (mean: 16 ± 1.54) days.Results:Changes in FA and AD in 48 brain regions occurring during stroke rehabilitation are described in relation to motor recovery. In this case series, one patient with a hemipontine infarct showed an increase in FA of the ipsilateral and contralateral corticospinal tract, whereas other patients with lesions involving the corona radiata and middle cerebral artery showed widespread decreases in perilesional FA. On the whole, FA and AD seemed to behave inversely to each other.Conclusions:This case series describes longitudinal changes in perilesional and remote FA and AD in relation to kinematic parameters of elbow flexion at the subacute post-stroke period. Although studies with larger sample sizes are needed, our findings indicate that longitudinally measured changes in DTI-based measurements of white matter microstructural integrity may aid in the prognostication of patients affected by motor stroke.