Aberrant age-related alterations in spontaneous cortical activity in participants with cerebral palsy.

Introduction: Cerebral Palsy (CP) is the most common neurodevelopmental motor disability, resulting in life-long sensory, perception and motor impairments. Moreover, these impairments appear to drastically worsen as the population with CP transitions from adolescents to adulthood, although the underlying neurophysiological mechanisms remain poorly understood. Methods: We began to address this knowledge gap by utilizing magnetoencephalographic (MEG) brain imaging to study how the amplitude of spontaneous cortical activity (i.e., resting state) is altered during this transition period in a cohort of 38 individuals with spastic diplegic CP (Age range = 9.80-47.50 years, 20 females) and 67 neurotypical controls (NT) (Age range = 9.08-49.40 years, Females = 27). MEG data from a five-minute eyes closed resting-state paradigm were source imaged, and the power within the delta (2-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta (15-29 Hz), and gamma (30-59 Hz) frequency bands were computed. Results: For both groups, the delta and theta spontaneous power decreased in the bilateral temporoparietal and superior parietal regions with age, while alpha, beta, and gamma band spontaneous power increased in temporoparietal, frontoparietal and premotor regions with age. We also found a significant group x age interaction, such that participants with CP demonstrated significantly less age-related increases in the spontaneous beta activity in the bilateral sensorimotor cortices compared to NT controls. Discussion: Overall, these results demonstrate that the spontaneous neural activity in individuals with CP has an altered trajectory when transitioning from adolescents to adulthood. We suggest that these differences in spontaneous cortical activity may play a critical role in the aberrant motor actions seen in this patient group, and may provide a neurophysiological marker for assessing the effectiveness of current treatment strategies that are directed at improving the mobility and sensorimotor impairments seen in individuals with CP.

Youth with Cerebral Palsy Display Abnormal Somatosensory Cortical Activity During a Haptic Exploration Task.

There are numerous clinical reports that youth with cerebral palsy (CP) have proprioceptive, stereognosis and tactile discrimination deficits. The growing consensus is that the altered perceptions in this population are attributable to aberrant somatosensory cortical activity seen during stimulus processing. It has been inferred from these results that youth with CP likely do not adequately process ongoing sensory feedback during motor performance. However, this conjecture has not been tested. Herein, we address this knowledge gap using magnetoencephalographic (MEG) brain imaging by applying electrical stimulation to the median nerve of youth with CP (N = 15, Age = 15.8 ± 0.83 yrs, Males = 12, MACS levels I-III) and neurotypical (NT) controls (N = 18, Age = 14.1 ± 2.4 yrs, Males = 9) while at rest (i.e., passive) and during a haptic exploration task. The results illustrated that the somatosensory cortical activity was reduced in the group with CP compared to controls during the passive and haptic conditions. Furthermore, the strength of the somatosensory cortical responses during the passive condition were positively associated with the strength of somatosensory cortical responses during the haptic condition (r = 0.75, P = 0.004). This indicates that the aberrant somatosensory cortical responses seen in youth with CP during rest are a good predictor of the extent of somatosensory cortical dysfunction during the performance of motor actions. These data provide novel evidence that aberrations in somatosensory cortical function in youth with CP likely contribute to the difficulties in sensorimotor integration and the ability to effectively plan and execute motor actions.

Val66Met Polymorphism Is Associated with Altered Motor-Related Oscillatory Activity in Youth with Cerebral Palsy.

Brain-derived neurotrophic factor (BDNF) plays a critical role in the capacity for neuroplastic change. A single nucleotide polymorphism of the BDNF gene is well known to alter the activity-dependent release of the protein and may impact the capacity for neuroplastic change. Numerous studies have shown altered sensorimotor beta event-related desynchronization (ERD) responses in youth with cerebral palsy (CP), which is thought to be directly related to motor planning. The objective of the current investigation was to use magnetoencephalography (MEG) to evaluate whether the BDNF genotype affects the strength of the sensorimotor beta ERD seen in youth with CP while youth with CP performed a leg isometric target matching task. In addition, we collected saliva samples and used polymerase chain reaction (PCR) amplification to determine the status of the amino acid fragment containing codon 66 of the BDNF gene. Our genotyping results identified that 25% of the youth with CP had a Val66Met or Met66Met polymorphism at codon 66 of the BDNF gene. Furthermore, we identified that the beta ERD was stronger in youth with CP who had the Val66Met or Met66Met polymorphism in comparison to those without the polymorphism (p = 0.042). Overall, these novel findings suggest that a polymorphism at the BDNF gene may alter sensorimotor cortical oscillations in youth with CP.

Therapeutic Lower Extremity Power Training Alters the Sensorimotor Cortical Activity of Individuals With Cerebral Palsy.

Objective: To utilize magnetoencephalographic (MEG) brain imaging to examine potential changes in sensorimotor cortical oscillations after therapeutic power training in individuals with cerebral palsy (CP). Design: Cohort. Setting: Academic medical center. Participants: Individuals with CP (N=11; age=15.9±1.1 years; Gross Motor Function Classification System I- III) and neurotypical controls (NTs; N=16; age=14.6±0.8 years). Interventions: Participants with CP underwent 24 (8 weeks; 3 days a week) sessions of high-velocity lower extremity power training on a leg press. The NTs underwent single baseline MEG assessments. Main Outcome Measures: Pre-post bilateral leg press 1-repetition maximum and peak power production were used to assess the muscular performance changes. The 10-m walk and 1-minute walk tests were used to assess mobility changes. During MEG recordings, participants used their right leg to complete a goal-directed isometric target-matching task. Advanced beamforming methods were subsequently used to image the strength of the sensorimotor beta oscillatory power. Results: Before the therapeutic power training, the participants with CP had stronger beta sensorimotor cortical oscillations compared with the NT controls. However, the beta sensorimotor cortical oscillations were weaker and approximated the controls after the participants with CP completed the therapeutic power training protocol. There also was a link between the amount of improvement in leg peak power production and the amount of reduction in sensorimotor cortical oscillations seen after therapy. Conclusions: Therapeutic power training appears to optimize the sensorimotor cortical oscillations of individuals with CP, and these neuroplastic changes partly contribute to improvements in the leg peak power production of individuals with CP. Therapeutic power training might provide the key ingredients for beneficial neuroplastic change.

Power training alters somatosensory cortical activity of youth with cerebral palsy.

OBJECTIVE: Our prior magnetoencephalographic (MEG) investigations demonstrate that persons with cerebral palsy (CP) have weaker somatosensory cortical activity than neurotypical (NT) controls, which is associated with reduced muscular strength and mobility. Power training can improve lower extremity isokinetic strength, muscular power, and walking performance of youth with CP. Potentially, these clinically relevant improvements are partially driven by changes in somatosensory processing. The objective of this investigation was to determine if power training has complementary changes in muscular function and somatosensory cortical activity in youth with CP. METHODS: A cohort of youth with CP (N = 11; age = 15.90 ± 1.1 years) and NT controls (N = 10; Age = 15.93 ± 2.48 years) participated in this investigation. Youth with CP underwent 24 power training sessions. Pre-post bilateral leg press 1-repetition maximum (1RM), peak power production, 10-m walking speed, and distance walked 1-min were used as outcome measures. MEG neuroimaging assessed the changes in somatosensory cortical activity while at rest. NT controls only underwent a baseline MEG assessment. RESULTS: Youth with CP had a 56% increase in 1RM (p < 0.001), a 33% increase in peak power production (p = 0.019), and a 4% improvement in 1-min walk (p = 0.029). Notably, there was a 46% increase in somatosensory cortical activity (p = 0.02). INTERPRETATION: These results are the first to show that power training is associated with improvements in muscular function, walking performance, and the resting somatosensory cortical activity in individuals with CP. This treatment approach might be advantageous due to the potential to promote cortical and muscular plasticity, which appear to have carryover effects for improved walking performance.

Cortical oscillations that underlie working memory are altered in adults with cerebral palsy.

OBJECTIVE: This investigation used magnetoencephalography (MEG) to identify the neurophysiological mechanisms contributing to the altered cognition seen in adults with cerebral palsy (CP). METHODS: Adults with CP (GMFCS levels I-IV) and demographically-matched controls completed a Sternberg-type working memory task during MEG. Secondarily, they completed the National Institutes of Health (NIH) cognitive toolbox. Beamforming was used to image the significant MEG oscillatory responses and the resulting images were examined using statistical parametric mapping to identify cortical activity that differed between groups. RESULTS: Both groups had a left-lateralized decrease in alpha-beta (11-16 Hz) power across the occipital, temporal, and prefrontal cortices during encoding, as well as an increase in alpha (9-13 Hz) power across the occipital cortices during maintenance. The strength of alpha-beta oscillations in the prefrontal cortices were weaker in those with CP during encoding. Weaker alpha-beta oscillation within the prefrontal cortex was associated with poorer performance on the NIH toolbox and a higher GMFCS level. CONCLUSIONS: Alpha-beta aberrations may impact the basic encoding of information in adults with CP, which impacts their overall cognition. Altered alpha-beta oscillation might be connected with gross motor function. SIGNIFICANCE: This experimental work highlights the aberrant alpha-beta during encoding as possible neurophysiological mechanism of the cognitive deficiencies.

Motor beta cortical oscillations are related with the gait kinematics of youth with cerebral palsy.

OBJECTIVE: It is widely believed that the perinatal brain injuries seen in youth with cerebral palsy (CP) impact neuronal processing of sensory information and the production of leg motor actions during gait. However, very limited efforts have been made to evaluate the connection between neural activity within sensorimotor networks and the altered spatiotemportal gait biomechanics seen in youth with CP. The objective of this investigation was to use magnetoencephalographic (MEG) brain imaging and biomechanical analysis to probe this connection. METHODS: We examined the cortical beta oscillations serving motor control of the legs in a cohort of youth with CP (N = 20; Age = 15.5 ± 3 years; GMFCS levels I-III) and healthy controls (N = 15; Age = 14.1 ± 3 years) using MEG brain imaging and a goal-directed isometric knee target-matching task. Outside the scanner, a digital mat was used to quantify the spatiotemporal gait biomechanics. RESULTS: Our MEG imaging results revealed that the participants with CP exhibited stronger sensorimotor beta oscillations during the motor planning and execution stages compared to the controls. Interestingly, we also found that those with the strongest sensorimotor beta oscillations during motor execution also tended to walk slower and have a reduced cadence. INTERPRETATION: These results fuel the impression that the beta sensorimotor cortical oscillations that underlie leg musculature control may play a central role in the altered mobility seen in youth with CP.

Gamma somatosensory cortical oscillations are attenuated during the stance phase of human walking.

It is well appreciated that processing of peripheral feedback by the somatosensory cortices plays a prominent role in the control of human motor actions like walking. However, very few studies have actually quantified the somatosensory cortical activity during walking. In this investigation, we used electroencephalography (EEG) and beamforming source reconstruction methods to quantify the frequency specific neural oscillations that are induced by an electrical stimulation that is applied to the right tibial nerve under the following experimental conditions: 1) sitting, 2) standing in place, and 3) treadmill walking. Our experimental results revealed that the peripheral stimulation induced a transient increase in theta-alpha (4-12 Hz; 50-350 ms) and gamma (40-80 Hz; 40-100 ms) activity in the leg region of the contralateral somatosensory cortices. The strength of the gamma oscillations were similar while sitting and standing, but were markedly attenuated while walking. Conversely, the strength of the theta-alpha oscillations were not different across the respective experimental conditions. Prior research suggests the afferent feedback from the Ia sensory fibers are likely attenuated during walking, while afferent feedback from the ß polysynaptic sensory fibers are not. We suggest that the attenuated gamma oscillations seen during walking reflect the gating of the Ia afferents, while the similarity of theta-alpha oscillations across the experimental conditions is associated with the afferent information from the type II (Aα and ß) polysynaptic sensory fibers.