Changes In Corticospinal Tract Research Articles

Diffusion Spectrum Imaging of Corticospinal Tracts in Idiopathic Normal Pressure Hydrocephalus.

Purpose: The purpose of this study was to measure the diffusion spectrum imaging (DSI) parameters of corticospinal tracts (CSTs) and evaluate diffusional changes in CSTs in patients with idiopathic normal pressure hydrocephalus (iNPH) by DSI.Methods: Twenty-three iNPH patients and twenty-one healthy controls (HCs) were involved in this study. Brain DSI data for all participants were collected through the same MR scanning procedure. The diffusion parameters measured and analyzed included quantitative anisotropy (QA), the isotropic diffusion component (ISO), general fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of corticospinal tracts.Results: The QA and ISO values of corticospinal tracts in iNPH patients were significantly lower than those in HCs (PLQA = 0.008, PRQA = 0.016, PLISO = 0.024, PRISO = 0.016). The mean MD, AD, and RD values in iNPH patients were significantly higher than those in HCs (PMD = 0.032, PAD = 0.032, PRD = 0.048,). No significant differences in GFA and FA values were noted between iNPH patients and HCs.Conclusion: Decreased QA and ISO values of corticospinal tracts were found in iNPH patients. Quantitative CST evaluation using DSI may lead to information that can improve the present understanding of the disease mechanism.

Detecting Corticospinal Tract Impairment in Tumor Patients With Fiber Density and Tensor-Based Metrics.

Tumors infiltrating the motor system lead to significant disability, often caused by corticospinal tract injury. The delineation of the healthy-pathological white matter (WM) interface area, for which diffusion magnetic resonance imaging (dMRI) has shown promising potential, may improve treatment outcome. However, up to 90% of white matter (WM) voxels include multiple fiber populations, which cannot be correctly described with traditional metrics such as fractional anisotropy (FA) or apparent diffusion coefficient (ADC). Here, we used a novel fixel-based along-tract analysis consisting of constrained spherical deconvolution (CSD)-based probabilistic tractography and fixel-based apparent fiber density (FD), capable of identifying fiber orientation specific microstructural metrics. We addressed this novel methodology’s capability to detect corticospinal tract impairment. We measured and compared tractogram-related FD and traditional microstructural metrics bihemispherically in 65 patients with WHO grade III and IV gliomas infiltrating the motor system. The cortical tractogram seeds were based on motor maps derived by transcranial magnetic stimulation. We extracted 100 equally distributed cross-sections along each streamline of corticospinal tract (CST) for along-tract statistical analysis. Cross-sections were then analyzed to detect differences between healthy and pathological hemispheres. All metrics showed significant differences between healthy and pathologic hemispheres over the entire tract and between peritumoral segments. Peritumoral values were lower for FA and FD, but higher for ADC within the entire cohort. FD was more specific to tumor-induced changes in CST than ADC or FA, whereas ADC and FA showed higher sensitivity. The bihemispheric along-tract analysis provides an approach to detect subject-specific structural changes in healthy and pathological WM. In the current clinical dataset, the more complex FD metrics did not outperform FA and ADC in terms of describing corticospinal tract impairment.

Prediction of Motor Recovery after Stroke by Assessment of Corticospinal Tract Wallerian Degeneration Using Diffusion Tensor Imaging.

Aim of the Study To predict motor recovery after stroke by detection of diffusion tensor imaging (DTI) fractional anisotropy (FA) changes of corticospinal tract (CST) and correlate findings with clinical scores to provide more effective treatment and rehabilitation. Subjects and Methods Thirty patients with cerebral stroke were enrolled and underwent conventional magnetic resonance imaging and DTI at admission and 1 month after stroke. Mean diffusivity (MD), FA, FA ratio (rFA), and fiber number (FN) values of CST were calculated at the pons at admission and after 1 month of stroke. Three-dimensional reconstruction of bilateral CST and the structural changes of fibrous bands were observed. Severity of limb weakness was assessed by using the motor sub-index scores of the National Institutes of Health Stroke Scale (NIHSS) at admission, and after 1, 6, and 9 months for severity of limb weakness. Results The mean age of our patients was 61.32 ± 4.34 years, 17/30 (56.6%) were females, and 13/30 (43.4%) were males. In our study, 18/30 (60%) were hypertensive, 19/30 (63.3%) were diabetic, and 12/30 (40%) were smokers. A significant negative correlation was found between rFA and FN in the ipsilateral CST of the cerebral infarction at the rostral part of pons after 1 month of infarction and NIHSS score at 6 months ( r = 0.377, p = 0.04 and r = 0.237, p = 0.02, respectively). However, a positive insignificant correlation was found between MD and NIHSS ( r = 0.345, p = 0.635). The initial NIHSS score at the time of injury was 19.2 ± 4.3, which changed to 7.9 ± 2.4, 4.6 ± 1.9, and 3.3 ± 1.4 at 1, 6, and 9 months, respectively. Conclusion DTI is a sensitive tool for early detection of Wallerian degeneration in the CST after stroke, and can predict motor performance to provide effective treatment and rehabilitation to improve quality of life.

Corticospinal tract abnormalities and ventricular dilatation: A transdiagnostic comparative tractography study

BackgroundMicrostructural alterations of corticospinal tract (CST) have been found in idiopathic normal pressure hydrocephalus (iNPH). No study, however, investigated the effect of ventricular dilatation on CST in Progressive Supranuclear Palsy (PSP). ObjectiveThe aim of this study was to investigate CST diffusion profile in a large cohort of PSP patients with and without ventricular dilatation. MethodsTwenty-three iNPH patients, 87 PSP patients and 26 controls were enrolled. Evans index (EI) and ventricular volume (VV) were measured in all patients. CST tractography was performed to calculate FA, MD, AxD and RD in six different anatomical regions: medulla oblungata (MO), pons (P), cerebral peduncle (CP), posterior limb of internal capsule (PLIC), corona radiata (CR), subcortical white matter (SWM). ANCOVA was used for comparing CST diffusion profiles between the groups and association between CST microstructural metrics and measures of ventricular dilatation (EI and VV) was assessed. ResultsThirty-three PSP patients had ventricular dilatation (EI > 0.30, PSP-vd) while 54 PSP patients had normal ventricular system (EI ≤ 0.30, PSP-wvd). iNPH patients had the most marked FA and AxD increase in PLIC and CR of CST followed by PSP-vd, PSP-wvd and controls; RD was altered only in iNPH. A strong correlation was found between CST diffusion metrics and EI or VV. ConclusionsOur findings confirm the microstructural changes of CST in iNPH patients and demonstrate for the first time similar alterations in PSP-vd patients, suggesting a crucial role of ventricular dilatation in the mechanical compression of CST.

The sequence of structural, functional and cognitive changes in multiple sclerosis

BackgroundAs disease progression remains poorly understood in multiple sclerosis (MS), we aim to investigate the sequence in which different disease milestones occur using a novel data-driven approach. MethodsWe analysed a cohort of 295 relapse-onset MS patients and 96 healthy controls, and considered 28 features, capturing information on T2-lesion load, regional brain and spinal cord volumes, resting-state functional centrality (“hubness”), microstructural tissue integrity of major white matter (WM) tracts and performance on multiple cognitive tests. We used a discriminative event-based model to estimate the sequence of biomarker abnormality in MS progression in general, as well as specific models for worsening physical disability and cognitive impairment. ResultsWe demonstrated that grey matter (GM) atrophy of the cerebellum, thalamus, and changes in corticospinal tracts are early events in MS pathology, whereas other WM tracts as well as the cognitive domains of working memory, attention, and executive function are consistently late events. The models for disability and cognition show early functional changes of the default-mode network and earlier changes in spinal cord volume compared to the general MS population. Overall, GM atrophy seems crucial due to its early involvement in the disease course, whereas WM tract integrity appears to be affected relatively late despite the early onset of WM lesions. ConclusionData-driven modelling revealed the relative occurrence of both imaging and non-imaging events as MS progresses, providing insights into disease propagation mechanisms, and allowing fine-grained staging of patients for monitoring purposes

Quantitative tractography reveals changes in the corticospinal tract in drug-naïve children with attention-deficit/hyperactivity disorder

The specific role of the corticospinal tract with respect to inattention and impulsive symptoms in children with attention-deficit/hyperactivity disorder (ADHD) has been explored in the past. However, to our knowledge, no study has identified the exact regions of the corticospinal tract that are affected in ADHD. We aimed to determine comprehensive alterations in the white matter microstructure of the corticospinal tract and underlying neuropsychological substrates in ADHD. We recruited 38 drug-naïve children with ADHD and 34 typically developing controls. We employed a tract-based quantitative approach to measure diffusion parameters along the trajectory of the corticospinal tract, and we further correlated alterations with attention and response inhibition measures. Compared with controls, children with ADHD demonstrated significantly lower fractional anisotropy and higher radial diffusivity at the level of cerebral peduncle, and higher fractional anisotropy at the level of the posterior limb of the internal capsule in the right corticospinal tract only. As well, increased fractional anisotropy in the posterior limb of the internal capsule was negatively correlated with continuous performance test attention quotients and positively correlated with reaction time on the Stroop Colour–Word Test; increased radial diffusivity in the right peduncle region was positively correlated with omissions in the Stroop test. The sample size was relatively small. Moreover, we did not consider the different subtypes of ADHD and lacked sufficient power to analyze subgroup differences. Higher-order diffusion modelling is needed in future white matter studies. We demonstrated specific changes in the right corticospinal tract in children with ADHD. Correlations with measures of attention and response inhibition underscored the functional importance of corticospinal tract disturbance in ADHD.

Abstract WP199: Change of Corticospinal Tract Integrity and 6-month Motor Outcome After Stroke: DTI Study

Objective: Corticospinal tract (CST) changes with time after stroke. However, few studies have investigated longitudinal change of CST and its relationship with motor outcomes. Primary goal of this study is to investigate the changes of CST after stroke using diffusion tensor image (DTI) and the relationship between CST changes and functional motor outcome in upper and lower extremities at 6 months after onset of stroke. Methods: We collected data from STroke Outcome Prediction (STOP) database that is prospective data collecting system for functional recovery prediction after stroke based on neuroimaging study. Fifty-five patients with first-ever stroke who performed functional assessment and underwent DTI at 30 days and 6 months poststroke were included. Clinical evaluation included Fugl-Meyer Assessment (FMA), Manual Function Test (MFT), Berg Balance Scale (BBS), and Functional Ambulation Category (FAC). DTI parameters were fiber number (FN), average fiber length (AL), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), laterality index (LI) and delta (Δ) changes of these values. Also type of CST by diffusion tensor tractography was included for analysis. Results: FA decreased and diffusivity indices (AD, MD, RD) increased in ipsilesional hemisphere; Decrease of FA and increase of RD were also noted in contralesional side. Type of CST were changed in 19 patients (34.6%). Spearman correlation analysis showed strong correlations between DTI values (FN, AL, FA, RD) and motor outcomes (FMA, MFT, BBS, FAC) at 30 days and 6 months. However, ΔFA or ΔRD did not show significant correlation with Δ changes of motor outcomes. In the CART analysis, overall prediction accuracy of DTI parameters for 6-month motor outcome ranged from 81.8 to 90.9 %. Conclusion: The integrity of CST changed not only on the lesion side but also on contralesional side. Integrity of CST using DTI at early phase of rehabilitation is useful to predict 6-month motor outcome after stroke. Acknowledgement: No potential conflict of interests relevant to this article were reported. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1A2C2003020).

White matter changes in corticospinal tract associated with improvement in arm and hand functions in incomplete cervical spinal cord injury: pilot case series.

This is a prospective clinical pilot case series. Improvement of arm and hand functions after spinal cord injury (SCI) is one of the major rehabilitation goals. Electrical stimulation of the primary motor cortex via transcranial direct current stimulation (tDCS) coupled with high-intensity repetitive motor training may have potential to facilitate improvement in motor function in chronic, incomplete cervical SCI. We investigated the relationship between motor recovery and changes in white matter integrity in response to treatment intervention. This study was conducted in The Institute for Rehabilitation and Research Memorial Hermann, Houston, USA. Four right-handed adults with chronic, incomplete cervical SCI (age, 36-63 years, American Spinal Injury Association Impairment Scale grade C-D) were enrolled in 10 sessions of anodal tDCS at 2 mA versus sham tDCS followed by 1 h of robotic-assisted arm training. Changes in arm and hand function were measured with Jebsen-Taylor Hand Function Test and Motor Activity Log-Amount of Use. Diffusion tension imaging was used to measure changes in fractional anisotropy (FA) of corticospinal tracts (CSTs). After 10 sessions of treatment, we found greater improvement in hand function and hand usage in patients who received active tDCS treatment versus sham treatment. There was an overall positive change in FA values across all patients. We show changes in arm and hand function associated with changes in CST tractographic mapping to quantify the motor system components in chronic incomplete cervical SCI.

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade.

Psychotic symptoms are core clinical features of schizophrenia. We tested recent hypotheses proposing that psychotic, or positive, symptoms stem from irregularities in long-range white matter tracts projecting into the frontal cortex, and we predicted that selective dopamine D2/3 receptor blockade would restore white matter. Between December 2008 and July 2011, antipsychotic-naive patients with first-episode schizophrenia and matched healthy controls underwent baseline examination with 3 T MRI diffusion tensor imaging and clinical assessments. We assessed group differences of fractional anisotropy (FA) using voxelwise tract-based spatial statistics (TBSS) and anatomic region of interest (ROI)-based analyses. Subsequently, patients underwent 6 weeks of antipsychotic monotherapy with amisulpride. We repeated the examinations after 6 weeks. We included 38 patients with first-episode schizophrenia and 38 controls in our analysis, and 28 individuals in each group completed the study. At baseline, whole brain TBSS analyses revealed lower FA in patients in the right anterior thalamic radiation (ATR), right cingulum, right inferior longitudinal fasciculus and right corticospinal tract (CT). Fractional anisotropy in the right ATR correlated with positive symptoms (z = 2.64, p= 0.008). The ROI analyses showed significant associations between positive symptoms and FA of the frontal fasciculi, specifically the right arcuate fasciculus (z = 2.83, p= 0.005) and right superior longitudinal fasciculus (z = -3.31, p= 0.001). At re-examination, all correlations between positive symptoms and frontal fasciculi had resolved. Fractional anisotropy in the ATR increased more in patients than in controls (z = -4.92, p< 0.001). The amisulpride dose correlated positively with FA changes in the right CT (t= 2.52, p= 0.019). Smoking and a previous diagnosis of substance abuse were potential confounders. Long-term effects of amisulpride on white matter were not evaluated. Antipsychotic-naive patients with schizophrenia displayed subtle deficits in white matter, and psychotic symptoms appeared specifically associated with frontal fasciculi integrity. Six weeks of amisulpride treatment normalized white matter. Potential remyelinating effects of dopamine D2/3 receptor antagonism warrant further clarification.

Differential Expression of Secreted Phosphoprotein 1 in the Motor Cortex among Primate Species and during Postnatal Development and Functional Recovery

We previously reported that secreted phosphoprotein 1 (SPP1) mRNA is expressed in neurons whose axons form the corticospinal tract (CST) of the rhesus macaque, but not in the corresponding neurons of the marmoset and rat. This suggests that SPP1 expression is involved in the functional or structural specialization of highly developed corticospinal systems in certain primate species. To further examine this hypothesis, we evaluated the expression of SPP1 mRNA in the motor cortex from three viewpoints: species differences, postnatal development, and functional/structural changes of the CST after a lesion of the lateral CST (l-CST) at the mid-cervical level. The density of SPP1-positive neurons in layer V of the primary motor cortex (M1) was much greater in species with highly developed corticospinal systems (i.e., rhesus macaque, capuchin monkey, and humans) than in those with less developed corticospinal systems (i.e., squirrel monkey, marmoset, and rat). SPP1-positive neurons in the macaque monkey M1 increased logarithmically in layer V during postnatal development, following a time course consistent with the increase in conduction velocity of the CST. After an l-CST lesion, SPP1-positive neurons increased in layer V of the ventral premotor cortex, in which compensatory changes in CST function/structure may occur, which positively correlated with the extent of finger dexterity recovery. These results further support the concept that the expression of SPP1 may reflect functional or structural specialization of highly developed corticospinal systems in certain primate species.

Structural brain changes after 4 wk of unilateral strength training of the lower limb

Strength training enhances muscular strength and neural drive, but the underlying neuronal mechanisms remain unclear. This study used magnetic resonance imaging (MRI) to identify possible changes in corticospinal tract (CST) microstructure, cortical activation, and subcortical structure volumes following unilateral strength training of the plantar flexors. Mechanisms underlying cross-education of strength in the untrained leg were also investigated. Young, healthy adult volunteers were assigned to training (n = 12) or control (n = 9) groups. The 4 wk of training consisted of 16 sessions of 36 unilateral isometric plantar flexions. Maximum voluntary isometric contraction torque was tested pre- and posttraining. MRI investigation included a T1-weighted scan, diffusion tensor imaging and functional MRI. Probabilistic fiber tracking of the CST was performed on the diffusion tensor imaging images using a two-regions-of-interest approach. Fractional anisotropy and mean diffusivity were calculated for the left and right CST in each individual before and after training. Standard functional MRI analyses and volumetric analyses of subcortical structures were also performed. Maximum voluntary isometric contraction significantly increased in both the trained and untrained legs of the training group, but not the control group. A significant decrease in mean diffusivity was found in the left CST following strength training of the right leg. No significant changes were detected in the right CST. No significant changes in cortical activation were observed following training. A significant reduction in left putamen volume was found after training. This study provides the first evidence for strength training-related changes in white matter and putamen in the healthy adult brain.

Changes in Corticospinal Function and Ankle Motor Control during Recovery from Incomplete Spinal Cord Injury

Little is known about the mechanisms that underlie motor recovery after incomplete spinal cord injury (iSCI) in humans. This study assessed changes in corticospinal tract (CST) function by measuring motor-evoked potentials (MEPs) and ankle motor control at 1, 3, and 6 months after acute iSCI. In 12 iSCI patients and matched controls, MEPs (evoked at 20% of maximal voluntary contraction [MVC]) were combined with a comprehensive ankle motor assessment protocol that measured ankle dorsiflexor strength (MVC, manual muscle testing, maximal movement velocity [MMV]), dexterity (the ability to accurately time ankle dorsiflexion movements) and gait (speed, walking aids). In the first 6 months after iSCI, all measures of muscle strength, gait and the MEP amplitudes significantly increased. The level of background electromyography (EMG) at 20% MVC remained stable, although absolute MVC increased. The MEP latencies were significantly delayed and remained unchanged during the first 6 months after iSCI. In addition, dexterity was preserved throughout rehabilitation. The percentage increase in MEP amplitude was significantly related only to the percentage improvement in MMV. The finding of unchanged CST conductivity, as assessed by MEP latencies in acute iSCI patients recovering motor function, is in accordance with previous studies in human SCI on this issue. The increased MEP facilitation at stable background EMG might indicate improved synchronization of the descending volley and/or responsiveness of motoneurons to supra-spinal input. The absence of a relationship between MEP amplitudes and recovery of ambulation and muscle strength implies that plastic changes in spinal neural circuits and preserved motor units might have contributed to the functional improvement.

Corticospinal Tract Restoration

We tried to demonstrate the restoration of corticospinal tract in a patient with intracerebral hemorrhage, using diffusion tensor tractography and functional magnetic resonance imaging, and transcranial magnetic stimulation. Transcranial magnetic stimulation demonstrated the corticospinal tract had been spared since subacute stage. Diffusion tensor tractography and functional magnetic resonance imaging showed that the corticospinal tract that was displaced by a hematoma had been restored. These combined modalities would be helpful in elucidating the state and change of corticospinal tract.

Symmetric Temporal Abnormalities on MR Imaging in Amyotrophic Lateral Sclerosis with Dementia

Our aim was to clarify imaging findings of amyotrophic lateral sclerosis with dementia (ALSD). T2-weighted MR images (T2WI) of 3 patients with ALSD (2 men, 1 woman; 58-71 years of age) and 21 patients with ALS without dementia (12 men, 9 women; 46-74 years of age) were examined for frontotemporal lobar atrophy and signal-intensity alterations in the white matter of the anterior temporal lobes, corticospinal tracts (CST), and precentral gyri and in precentral cortices. The brain of one of the patients with ALSD was examined at autopsy. All patients with ALSD showed bilateral frontotemporal atrophy mostly with temporal lobe dominance. In the ALSD group, T2WI demonstrated hyperintensity in the subcortical white matter on the medial side of the anterior temporal lobes, whereas in the group without dementia, none showed this imaging finding. MR images demonstrated no abnormal signal-intensity changes in CST in the internal capsule or the brain stem in the ALSD group. In the group without dementia, 6 patients (28.6%) showed this imaging finding. In neuropathologic examinations of the brain of 1 patient with ALSD, myelin-stained sections of the brain demonstrated loss of myelin in the subcortical white matter on the medial side of the anterior temporal white matter. A symmetric pattern of frontotemporal atrophy and anteromedial subcortical hyperintensities in the temporal lobes on T2WI could be characteristic of ALSD.

Dynamic changes in corticospinal tracts after stroke detected by fibretracking

Background and aims: The integrity of motor pathways and functional connectivity patterns are important in assessing plastic changes related to successful recovery, to obtain prognostic information and to monitor future...

MRI demonstration of Wallerian degeneration in various intracranial lesions and its clinical implications

Dynamic signal intensity changes of Wallerian degeneration (WD) are well documented in cases of stroke. These changes have been staged I–IV, depending on time-specific signal intensity changes in corticospinal tract with magnetic resonance imaging (MRI). We performed both prospective and retrospective evaluation of various intracranial lesions to look for evidence of WD and to assess its prognostic implications. Eighteen patients of acute stroke were studied prospectively. Their functional disability was evaluated by using a modified Barthel index of activity of daily living (ADL) at presentation, at 1 month and at 4 months, and was correlated with presence or absence of WD on MRI. 10 18 patients showed signal intensity changes of WD on MRI and their mean ADL score changed from 9.1 at 1 month to 11.4 at 4 months duration suggestive of moderate to severe disability after 4 months of stroke. The rest of the eight patients, where MRI did not reveal signal intensity changes of WD, the mean ADL score improved from 10.37 at 1 month to 17.5 at 4 months, suggesting significant improvement in their clinical disability, 520 patients were studied retrospectively, out of whom 31 showed signal intensity changes of WD in various intracranial lesions, i.e. infarcts ( 14 220 ), intracranial haematoma ( 4 147 ), arterio-venous malformation ( 1 20 ), tumour ( 6 98 ), multiple sclerosis ( 5 20 ) and encephalitis ( 1 15 ). Presence of WD in these intracranial lesions correlated well with persistent clinical disability. This observation has immense prognostic value, particularly in relapsing and remitting disease like multiple sclerosis. We conclude that WD can be seen secondary to any CNS insult with MRI and its presence correlates well with persistent functional disability. It thus has prognostic value. © 1997 Elsevier Science B.V. All rights reserved.

Sparing of skilled forelimb reaching and corticospinal projections after neonatal motor cortex removal or hemidecortication in the rat: support for the Kennard doctine

Skilled forelimb use in reaching for food was studied in rats with variously sized and placed unilateral cortical lesions given in adulthood or on the day of birth. Fluorescent retrograde labelling was used to document changes in corticospinal tracts. In free choice tests, preferential use of the limb ipsilateral to damage was induced by adult motor, but not parietal or occipital, cortex damage. Similar preference for the ipsilateral limb was induced by neonatal motor and parietal, but not occipital, cortex damage. In both adult and neonate groups success with the preferred limb decreased in proportion to the increase in lesion size. To force use of the non-preferred limb, a bracelet, which prevented reaching but not other movements, was attached to the forearm of the preferred forelimb. Success with the non-preferred limb was poorer than with the preferred limb and success again decreased in proportion to the increase in lesion size. Adult and neonatal rats were divided into 4 groups according to the extent of motor cortex damage. Across all lesion sizes the neonatal operates were significantly more successful than the adult operates and their reaching movements appeared more normal. Surprisingly, some rats with large adult motor cortex lesions or hemidecortications were able to reach. Slow-motion video analysis of reaching impairments in both adult and neonata groups showed that limb extension and food grasping were less impaired that limb retraction and adduction of the limb to the mouth. The results show that the integrity of a neocortical hemisphere is not essential for contralateral limb use in reaching, but contributes to successful use of the limb. Following neonatal lesions, facilitation may be promoted by the ipsilateral neocortex through an augmented ipsilateral corticofugal pathway.