Motor pathway injury in patients with periventricular leucomalacia and spastic diplegia.

Periventricular leucomalacia has long been investigated as a leading cause of motor and cognitive dysfunction in patients with spastic diplegic cerebral palsy. However, patients with periventricular leucomalacia on conventional magnetic resonance imaging do not always have motor dysfunction and preterm children without neurological abnormalities may have periventricular leucomalacia. In addition, it is uncertain whether descending motor tract or overlying cortical injury is related to motor impairment. To investigate the relationship between motor pathway injury and motor impairment, we conducted voxelwise correlation analysis using tract-based spatial statistics of white matter diffusion anisotropy and voxel-based-morphometry of grey matter injury in patients with periventricular leucomalacia and spastic diplegia (n = 43, mean 12.86 ± 4.79 years, median 12 years). We also evaluated motor cortical and thalamocortical connectivity at resting state in 11 patients using functional magnetic resonance imaging. The functional connectivity results of patients with spastic diplegic cerebral palsy were compared with those of age-matched normal controls. Since γ-aminobutyric acid(A) receptors play an important role in the remodelling process, we measured neuronal γ-aminobutyric acid(A) receptor binding potential with dynamic positron emission tomography scans (n = 27) and compared the binding potential map of the patient group with controls (n = 20). In the current study, white matter volume reduction did not show significant correlation with motor dysfunction. Although fractional anisotropy within most of the major white matter tracts were significantly lower than that of age-matched healthy controls (P < 0.05, family wise error corrected), fractional anisotropy mainly within the bilateral corticospinal tracts and posterior body and isthmus of the corpus callosum showed more significant correlation with motor dysfunction (P < 0.03) than thalamocortical pathways (P < 0.05, family-wise error corrected). Cortical volume of the pre- and post-central gyri and the paracentral lobule tended to be negatively correlated with motor function. The motor cortical connectivity was diminished mainly within the bilateral somatosensory cortex, paracentral lobule, cingulate motor area and visual cortex in the patient group. Thalamovisual connectivity was not diminished despite severe optic radiation injury. γ-Aminobutyric acid(A) receptor binding potential was focally increased within the lower extremity homunculus, cingulate cortex, visual cortex and cerebellum in the patient group (P < 0.05, false discovery rate corrected). In conclusion, descending motor tract injury along with overlying cortical volume reduction and reduced functional connectivity appears to be a leading pathophysiological mechanism of motor dysfunction in patients with periventricular leucomalacia. Increased regional γ-aminobutyric acid(A) receptor binding potential appears to result from a compensatory plasticity response after prenatal brain injury.

Exploring the Intra Entrepreneurship-Employee Engagement-Creativity Linkage and the Diverse Effects of Gender and Marital Status.

This research examines which of the sub-dimensions of intra entrepreneurship (innovativeness, pro-activeness, risk-taking), and corporate social responsibility (CSR) support affects employee engagement (organizational and job engagement), which leads to employee creativity. The study uses survey data from SME employees in South Korea and applies the Structural Equation Modeling (SEM)-Artificial Neural Network (ANN) approach, to find that innovativeness and CSR support affect creativity through mediating roles of organizational engagement and job engagement, where job engagement plays a mediating role in the relationship between organizational engagement and creativity. The study also examines how employee gender and marital status effects the relative importance of intra entrepreneurship, organizational engagement, and job engagement on creativity. Findings of ANN analysis evaluates the effects per group (male-unmarried, male-married, female-unmarried, female-married) and shows how the importance of organizational engagement, job engagement, CSR support and innovativeness differ for each group. Contribution to theory and practice are discussed.

Time-dependent effect of transcranial direct current stimulation on the enhancement of working memory.

The time-dependent effect of transcranial direct current stimulation (tDCS) on working memory was investigated by applying anodal stimulation over the left prefrontal cortex. This single-blind, sham-controlled crossover study recruited 15 healthy participants. A three-back verbal working-memory task was performed before, during, and 30 min after 1 mA anodal or sham tDCS. Anodal tDCS, compared with sham stimulation, significantly improved working-memory performance. Accuracy of response was significantly increased after 20 min of tDCS application, and was further enhanced after 30 min of stimulation. This effect was maintained for 30 min after the completion of stimulation. These results suggest that tDCS at 1 mA enhances working memory in a time-dependent manner for at least 30 min in healthy participants.

Is electrical stimulation beneficial for improving the paralytic effect of botulinum toxin type A in children with spastic diplegic cerebral palsy?

PURPOSE: The purpose of the present study was to investigate whether electrical stimulation (ES) improves the paralytic effect of botulinum toxin type A (BTX-A) and evaluate the differences between low frequency (LF) and high frequency (HF) ES in children with spastic diplegic cerebral palsy (CP). MATERIALS AND METHODS: Twenty-three children with spastic diplegia CP who had BTX-A injections into both gastrocnemius muscles were assessed. Following the toxin injection, electrical stimulation was given to 1 side of the injected muscles and a sham-stimulation to the other side for 30 min a day for 7 consecutive days [HFES (25Hz) to 11 children, LFES (4Hz) to 12 children]. The compound motor action potentials (CMAP) from the gastrocnemius muscle were assessed before injection and at 5 time points (days 3, 7, 14, 21, and 30) after injection. The clinical assessments of spasticity were performed before and 30 days after injection. RESULTS: The CMAP area became significantly lower in both LFES and HFES sides from 3 days after injection compared to baseline values. In other words, the CMAP area of the sham-stimulated side showed a significant decrease at 7 or 14 days after injection. However, there were no significant differences in clinical assessment of spasticity between the stimulated and sham-stimulated sides. CONCLUSION: Short-term ES in both LF and HF to the spastic muscles injected with BTX-A might induce earlier denervating action of BTX-A. However, it does not necessarily lead to clinical and electrophysiological benefits in terms of reduction of spasticity.

Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability.

PURPOSE: The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplained developmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We also aimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). MATERIALS AND METHODS: We collected clinical and CMA data from patients at Konyang University Hospital between September 2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. RESULTS: All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy, and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) were considered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than in those with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by 83.3% (15/18) of the patients with pathogenic CMA. CONCLUSION: Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequently found if patients have two or more clinical features in addition to DD/ID.

Virtual environment training system for rehabilitation of stroke patients with unilateral neglect: crossing the virtual street.

In this paper, we propose a system for training of stroke patients with unilateral neglect by using technology of virtual reality (VR). The proposed system is designed to compensate for unilateral neglect. This system contains the calibration of unilateral neglect and the training of this disease. The calibration procedure is implemented by aligning the virtual object at a subjective middle line. The training procedure is implemented by completing the missions that are used to keep the virtual avatar safe during crossing the street in a virtual environment. The results of this study show that the proposed system is effective to train unilateral neglect. The left to right ratio scores extracted from this system gradually decrease as the sessions of training are repeated. To validate the VR system parameters, the parameters are analyzed by correlation with those of traditional unilateral neglect assessment methods (such as the line bisection test and the cancellation test).

Diffusion-tensor magnetic resonance imaging in children with language impairment.

We evaluated the integrity of the white matter tract using diffusion-tensor magnetic resonance imaging in children with language impairments who exhibited a structurally normal brain on conventional magnetic resonance imaging, and compared it with age-matched normal children. After generating fractional anisotropy and color-coded vector maps, fractional anisotropy values of the major white matter tracts were measured in six locations and compared between the two groups. Compared with the normal control group, the fractional anisotropy values of children with language impairments showed a statistically significant reduction in the genu of the corpus callosum, which is rarely revealed on conventional magnetic resonance images. Our results suggest that delayed maturation of the white matter plays a partial role in the pathophysiological mechanisms of language impairments.

Soft tissue surgery for equinus deformity in spastic hemiplegic cerebral palsy: effects on kinematic and kinetic parameters.

The purpose of this study was to evaluate how soft tissue surgery for correcting equinus deformity affects the kinematic and kinetic parameters of the ankle and proximal joints. Sixteen children with spastic hemiplegic cerebral palsy and equinus deformities (age range 3-16 years) were included. Soft tissue surgeries were performed exclusively on the ankle joint area in all subjects. Using computerized gait analysis (Vicon 370 Motion Analysis System), the kinematic and kinetic parameters during barefoot ambulation were collected preoperatively and postoperatively. In all 16 children, the abnormally increased ankle plantar flexion and pelvis anterior tilting on the sagittal plane were significantly improved without a weakening of push-off (p < 0.05). In a group of 8 subjects with a recurvatum knee gait pattern before operation, the postoperative kinematic and kinetic parameters of the knee joint were significantly improved (p < 0.05). In a group of 8 subjects with ipsilateral pelvic external rotation before operation, the postoperative pelvic deviations on the transverse plane were significantly decreased (p < 0.05). These findings suggest that the soft tissue surgery for correcting equinus deformity improves not only the abnormal gait pattern of the ankle, but also that of the knee and pelvis.

Comparison of the ratio of upper to lower chest wall in children with spastic quadriplegic cerebral palsy and normally developed children.

The upper chest wall does not grow properly in children with spinal muscular atrophy (SMA) with paradoxical breathing. This suggests that long-term inability to take a deep breath in developing children may result in underdevelopment of the upper chest wall. In addition, a rapid and paradoxical breathing pattern is frequently observed in children with severe cerebral palsy (CP), which often corresponds to the underdevelopment of the upper chest wall. The present study is designed to evaluate the ratio of the upper to lower chest wall in children with severe spastic quadriplegic CP, compared with normal children. We compared normal children with children that had spastic quadriplegic CP who did not have kyphosis or scoliosis. Test subjects were matched in terms of age, height, and weight. The diameters of upper chest (D(apex)) and of lower chest (D(base)) were measured on the anteroposterior (AP) view of a chest X-ray and the D(apex) to D(base) ratio was calculated. In selected cases the forced vital capacity (FVC) was measured using a Wright Respirometer. The D(apex) to D(base) ratio was significantly lower in the CP group than in the control group (p < 0.001). The ratio increased linearly with age (p < 0.001) in both CP (R = 0.372) and control groups (R = 0.477). The FVC/preFVC showed significant correlation with the D(apex) to D(base) ratio (R = 0.542, p < 0.01). The results of this study suggest a deviation of optimal chest wall structure in children with spastic quadriplegic CP.

Clinical features and outcomes following bilateral lower limb amputation in Korea.

The objectives of this study were to evaluate the clinical features and outcomes of 43 bilateral lower limb amputees. The clinical features obtained included the causes of amputation, level of amputation, concurrent medical problems, and stump condition. Outcome measures were obtained using the activities of daily living (ADL) index, the Frenchay Activities Index (FAI), and mobility grading with prostheses or wheelchair. Of 33 amputees who were prosthetic ambulators, 22 (67%), mainly bilateral trans-tibial (TT) amputees, were community ambulators, and participated in activities which included stair-walking, and six of 11 household ambulators were combination trans-femoral (TF) and TT amputees. Of 10 amputees who were wheelchair ambulators, only one was able to perform wheelchair transfers independently and five were independent wheelchair ambulators. Using the ADL index and FAI, there was no significant difference in scores according to the level of amputation (p > 0.05), but the scores of community prosthetic ambulators were significantly higher than those of wheelchair ambulators (p < 0.05). Age was found to be negatively correlated with ADL index and FAI scores (r = -0.518 vs. r = -0.550) (p < 0.01). This study concludes that overall independence in ADL after bilateral lower limb amputation improved with young age and prosthetic mobility.

Posterior Deltoid-to-Triceps Tendon Transfer for Elbow Extension in a Tetraplegia Patient: A Case Report.

In tetraplegia patients, activities of daily living are highly dependent on the remaining upper limb functions. In other countries, upper limb reconstruction surgery to improve function has been applied to diverse cases, but few cases have been reported in Korea. The current authors experienced a case of posterior deltoid-to-triceps tendon transfer and rehabilitation in a complete spinal cord injury with a C6 neurologic level, and we introduce the case-a 36-year-old man-with a literature review. The patient's muscle strength in C5 C6 muscles were normal, but C7 muscles were trace, and the Spinal Cord Independence Measure III (SCIM III) score was 24. The tendon of the posterior deltoid was transferred to the triceps brachii muscle, and then the patient received comprehensive rehabilitative treatment. His C7 muscle strength in the right upper extremity was enhanced from trace to fair, and his SCIM III score improved to 29.

Functional Recovery after the Transplantation of Neurally Differentiated Mesenchymal Stem Cells Derived from Bone Marrow in a Rat Model of Spinal Cord Injury.

This study was designed to investigate functional recovery after the transplantation of mesenchymal stem cells (MSCs) or neurally differentiated MSCs (NMSCs) derived from bone marrow in a rat model of spinal cord injury (SCI). Sprague-Dawley rats were subjected to incomplete SCI using an NYU impactor to create a free drop contusion at the T9 level. The SCI rats were then classified into three groups; MSCs, NMSCs, and phosphate-buffered saline (PBS)-treated groups. The cells or PBS were administrated 1 week after SCI. Basso-Beattie-Bresnahan (BBB) locomotor rating scores were measured at 1-week intervals for 9 weeks. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were also recorded 8 weeks after transplantation. While transplantation of MSCs led to a clear tendency of motor recovery, NMSC-treated rats had significantly improved BBB scores and showed significantly shortened initial latency, N1 latency, and P1 latency of the SSEPs compared to PBS controls. In addition, 5-bromo-2-deoxyuridine (BrdU)-prelabeled MSCs costained for BrdU and glial fibrillary acidic protein (GFAP) or myelin basic protein (MBP) were found rostrally and caudally 5 mm each from the epicenter of the necrotic cavity 4 weeks after transplantation. These results suggest that neurally differentiated cells might be an effective therapeutic source for functional recovery after SCI.

Neurologic recovery according to early magnetic resonance imaging findings in traumatic cervical spinal cord injuries.

The aim of this study was to determine the usefulness of early magnetic resonance imaging findings in predicting neurologic recovery at or below the injured level in traumatic cervical spinal cord injuries. Thirty patients with traumatic cervical spinal cord injuries were included. All of the patients received a magnetic resonance imaging and a neurologic examination in the emergency room, within 7 days of injury and at 6 months following the injury. To quantify neurologic recovery below the injured level, we modified clinical scales, particularly the motor ratio and the sensory ratio. We used the neurologic level to quantify recovery around the injured level. We assessed neurologic recovery according to MRI patterns and lesion extents. The pure hemorrhagic MRI pattern was not observed. In edematous and mixed types, the improvement of neurologic levels was not significantly different. The motor ratio and sensory ratio improved significantly more in edematous type patients than in mixed type patients. Based on MRI lesion extent, the improvement of neurologic levels was not significantly different, and motor ratio and sensory ratio improved significantly more in those with one or two segments involved than in those with more than two segments involved. In conclusion, early MRI pattern and lesion extent after traumatic cervical spinal cord injury may provide important information to help predict neurologic recovery, especially below the injured level.

Biomechanical assessment with electromyography of post-stroke ankle plantar flexor spasticity.

Spasticity has been defined as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex (muscle tone). Muscle tone consists of mechanical-elastic characteristics, reflex muscle contraction and other elements. The aims of this study were to determine whether to assess spasticity quantitatively, and to characterize biomechanical and electromyographic spasticity assessment parameters. These assessment parameters were described by investigating the correlation between clinical measures and the response to passive sinusoidal movement with consecutive velocity increments. Twenty post-stroke hemiplegic patients and twenty normal healthy volunteers were included in the study. Five consecutive sinusoidal passive movements of the ankle were performed at specific velocities (60, 120, 180, and 240 degrees/ sec). We recorded the peak torque, work, and threshold angle using a computerized isokinetic dynamometer, and simultaneously measured the rectified integrated electromyographic activity. We compared these parameters both between groups and between different velocities. The peak torque, threshold angle, work, and rectified integrated electromyographic activity were significantly higher in the post-stroke spastic group at all angular velocities than in the normal control group. The threshold angle and integrated electromyographic activity increased significantly and linearly as angular velocity increased, but the peak torque and work were not increased in the post-stroke spastic group. Peak torque, work, and threshold angle were significantly correlated to the Modified Ashworth scale, but the integrated electromyographic activity was not. The biomechanical and electromyographic approach may be useful to quantitatively assess spasticity. However, it may also be very important to consider the different characteristics of each biomechanical parameter.

Over-expression of S100B protein in children with cerebral palsy or delayed development.

S100B protein plays a role in promoting the maturation of a variety of neurons in many different CNS regions. Behavioral dysfunction in S100B over-expressed transgenic mice and the chronic elevation of S100B in Down's syndrome and in schizophrenia suggest that S100B over-expression is related to abnormal brain function. Therefore, we believed that the over-expression of S100B protein might be implicated in developmental brain dysfunction. The purpose of this study was to evaluate the serum S100B protein levels in patients with developmental brain dysfunction, such as cerebral palsy and delayed development, and to determine the clinical relevance of serum S100B protein in these patients. The mean values of serum S100B protein were significantly increased in both conditions. Patients with cerebral palsy had a S100B protein level of 3455.8 +/- 5004.6 ng/L and those with delayed development of 2557.0 +/- 2321.0 ng/L, compared with a normal control level of 583.8 +/- 483.0 ng/L (P < 0.05). The over-expression of S100B (defined as the normal mean plus three standard deviations) was found in 47.1% of the total patient group (delayed development (47.5%) and cerebral palsy (47.0%)). The frequency of over-expression was not significantly related to clinical diagnosis, disease severity or to brain MRI findings. However, patients who had periventricular leukomalacia by brain MRI showed a wide range and very high levels of S100B exceeding 10,000 ng/L in some cases. These findings suggest that the pathogenesis implied by the over-expression of S100B protein during brain development may play a role in developmental brain dysfunction.

The characteristics of sit-to-stand transfer in young children with spastic cerebral palsy based on kinematic and kinetic data.

The aim of this study is to investigate the kinetic and kinematic characteristics of sit-to-stand transfer in children with spastic cerebral palsy (CP) in comparison with normal children. Fifteen spastic diplegic children, 12 spastic hemiplegic children and 21 normally developed children participated in this study. The sit-to-stand task was evaluated using a Motion analyzer (Vicon 370 MA with six infrared cameras). The consistent pattern of sit-to-stand transfer and six transitional points were identified in normal children. The motion analysis of sit-to-stand in children with CP showed slowness in the task, increased anterior pelvic tilting, and hip flexion during the task. An early abrupt knee extension was noted in diplegic children, as compared with normal controls. Decreased maximal knee extensor moment and decreased extensor power generation of the hip and knee joints were the major kinetic characteristics of the involved limbs of both diplegic and hemiplegic CP.

Selective posterior rhizotomy for lower extremity spasticity: how much and which of the posterior rootlets should be cut?

BACKGROUND: It is well known that selective posterior rhizotomy is effective for relieving spasticity associated with cerebral palsy. However, there is significant variation between surgeons in terms of how much and which of the posterior rootlets should be cut for the improvement of ambulatory function without causing adverse effects. METHODS: The study population was composed of 200 CP patients who underwent SPR more than 1 year before this study. The children were divided into 4 groups (Group A had their L1-S2 roots cut, Group B had the L2-S2 roots cut, Group C had the L2-S1 roots cut, and Group D had the L2-S1 roots and the unilateral S2 root cut). We assessed lower limb spasticity, passive range of motion, ambulatory function, and gait pattern in each group. RESULTS: Inclusion of L1 and S2 in the lesioning process of SPR was more effective at relieving spasticity in terms of hip adduction and ankle dorsiflexion respectively and improving ambulatory function (p < 0.01). Although lesioning of S2 carried a greater risk of urinary dysfunction, resection of less than 50% of S2 significantly improved ambulatory function without urinary complications (p < 0.01). Unilateral lesioning of S2 was an alternative option in selected cases with different amounts of spasticity in the ankles for the same purpose. CONCLUSIONS: We propose that L1 and S2 roots should be included in the lesioning process of SPR for effective improvement of gross motor function, but that resection of these roots should be less than 50% to prevent complications.

Anatomic motor point localization for the treatment of gastrocnemius muscle spasticity.

The location of the motor point of the gastrocnemius muscle was accurately defined relative to surrounding bony landmarks to facilitate the approach to the nerve of the gastrocnemius muscle during treatment for gastrocnemius muscle spasticity. Anatomic dissection of 40 cadaver knees was undertaken for morphometric measurement. The distances from the epicondyle of the femur to the motor branch, and from the motor branch to the motor point of the nerve to the medial head of the gastrocnemius muscle were 3.68 +/- 11.44 mm, and 37.79 +/- 7.80 mm, respectively; while those of the nerve to lateral head of the gastrocnemius muscle were 4.45 +/- 11.96 mm, and 32.16 +/- 4.64 mm, respectively. The tibial nerve lay 44.57 +/- 5.45% and 56.30 +/- 4.73% from the lateral margins of the epicondyle and the fibular head, respectively. Careful consideration of the morphometry of the motor point of the gastrocnemius muscle may provide accurate anatomical guidance, and hence reduce complications during the chemical blockage of these nerves.

Assessment of autonomic nervous system with analysis of heart rate variability in children with spastic cerebral palsy.

The purpose of this study was to investigate the function of the autonomic nervous system in children with spastic cerebral palsy (CP) through an analysis of heart rate variability (HRV) occurring with orthostatic stress. Twelve children with spastic CP and twelve normal children participated in this study. The echocardiogram (ECG) signals were recorded for 3 minutes in both the supine and 70 degrees C head-up tilt positions, and then the HRV signals underwent power spectrum analysis at each position. Two components were measured; a low- frequency (LF) component (0.05 - 0.15 Hz) primarily reflecting sympathetic activity during orthostatic stress and a high-frequency (HF) component (0.15 - 0.4 Hz) reflecting parasympathetic activity. In the supine position, there was no significant difference between any of the HRV components of the two groups. In the head-up tilt position, absolute and normalized LF were significantly increased and absolute HF was significantly decreased in the normal children (p < 0.05), but not in the children with spastic CP. The results of this study suggest that cardiac autonomic functions, such as vagal withdrawal and sympathetic activation which occur during head-up tilt position, are not sufficient to overcome the orthostatic stress arising in spastic CP children.

Increased GABA-A receptor binding and reduced connectivity at the motor cortex in children with hemiplegic cerebral palsy: a multimodal investigation using 18F-fluoroflumazenil PET, immunohistochemistry, and MR imaging.

UNLABELLED: γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). METHODS: We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. RESULTS: In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. CONCLUSION: Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.