Somatosensory Plasticity in Hemiplegic Cerebral Palsy Following Constraint Induced Movement Therapy.

BACKGROUND: Children with hemiplegic cerebral palsy (HCP) experience upper limb somatosensory and motor deficits. Although constraint-induced movement therapy (CIMT) improves motor function, its impact on somatosensory function remains underinvestigated. OBJECTIVE: The objective of this study was to evaluate somatosensory perception and related brain responses in children with HCP, before and after a somatosensory enhanced CIMT protocol, as measured using clinical sensory and motor assessments and magnetoencephalography. METHODS: Children with HCP attended a somatosensory enhanced CIMT camp. Clinical somatosensory (tactile registration, 2-point discrimination, stereognosis, proprioception, kinesthesia) and motor outcomes (Quality of Upper Extremity Skills [QUEST] Total/Grasp, Jebsen-Taylor Hand Function Test, grip strength, Assisting Hand Assessment), as well as latency and amplitude of magnetoencephalography somatosensory evoked fields (SEF), were assessed before and after the CIMT camp with paired sample t-tests or Wilcoxon signed-rank tests. RESULTS: Twelve children with HCP (mean age: 7.5 years, standard deviation: 2.4) participated. Significant improvements in tactile registration for the affected (hemiplegic) hand (Z = 2.39, P = 0.02) were observed in addition to statistically and clinically significant improvements in QUEST total (t = 3.24, P = 0.007), QUEST grasp (t = 3.24, P = 0.007), Assisting Hand Assessment (Z = 2.25, P = 0.03), and Jebsen-Taylor Hand Function Test (t = -2.62, P = 0.03). A significant increase in the SEF peak amplitude was also found in the affected hand 100 ms after stimulus onset (t = -2.22, P = 0.04). CONCLUSIONS: Improvements in somatosensory clinical function and neural processing in the affected primary somatosensory cortex in children with HCP were observed after a somatosensory enhanced CIMT program. Further investigation is warranted to continue to evaluate the effectiveness of a sensory enhanced CIMT program in larger samples and controlled study designs.

Complexity-Dependent Modulations of Beta Oscillations for Verbal and Nonverbal Movements.

Purpose The planning and execution of motor behaviors require coordination of neurons that are established through synchronization of neural activity. Movements are typically preceded by event-related desynchronization (ERD) in the beta range (15-30 Hz) primarily localized in the motor cortex, while movement onset is associated with event-related synchronization (ERS). It is hypothesized that ERD is important for movement preparation and execution, and ERS serves to inhibit movement and update the motor plan. The primary objective of this study was to determine to what extent movement-related oscillatory brain patterns (ERD and ERS) during verbal and nonverbal tasks may be affected differentially by variations in task complexity. Method Seventeen right-handed adult participants (nine women, eight men; M age = 25.8 years, SD = 5.13) completed a sequential button press and verbal task. The final analyses included data for 15 participants for the nonverbal task and 13 for the verbal task. Both tasks consisted of two complexity levels: simple and complex sequences. Magnetoencephalography was used to record modulations in beta band brain oscillations during task performance. Results Both the verbal and button press tasks were characterized by significant premovement ERD and postmovement ERS. However, only simple sequences showed a distinct transient synchronization during the premovement phase of the task. Differences between the two tasks were reflected in both latency and peak amplitude of ERD and ERS, as well as in lateralization of oscillations. Conclusions Both verbal and nonverbal movements showed a significant desynchronization of beta oscillations during the movement preparation and holding phase and a resynchronization upon movement termination. Importantly, the premovement phase for simple but not complex tasks was characterized by a transient partial synchronization. In addition, the data revealed significant differences between the two tasks in terms of lateralization of oscillatory modulations. Our findings suggest that, while data from the general motor control research can inform our understanding of speech motor control, significant differences exist between the two motor systems that caution against overgeneralization of underlying neural control processes.

White matter microstructural differences underlying beta oscillations during speech in adults who stutter.

The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen.

Individual differences in motor development during early childhood: An MEG study.

In a previous study, we reported the first measurements of pre-movement and sensorimotor cortex activity in preschool age children (ages 3-5 years) using a customized pediatric magnetoencephalographic system. Movement-related activity in the sensorimotor cortex differed from that typically observed in adults, suggesting that maturation of cortical motor networks was still incomplete by late preschool age. Here we compare these earlier results to a group of school age children (ages 6-8 years) including seven children from the original study measured again two years later, and a group of adults (mean age 31.1 years) performing the same task. Differences in movement-related brain activity were observed both longitudinally within children in which repeated measurements were made, and cross-sectionally between preschool age children, school age children, and adults. Movement-related mu (8-12 Hz) and beta (15-30 Hz) oscillations demonstrated linear increases in amplitude and mean frequency with age. In contrast, movement-evoked gamma synchronization demonstrated a step-like transition from low (30-50 Hz) to high (70-90 Hz) narrow-band oscillations, and this occurred at different ages in different children. Notably, pre-movement activity ('readiness fields') observed in adults was absent in even the oldest children. These are the first direct observations of brain activity accompanying motor responses throughout early childhood, confirming that maturation of this activity is still incomplete by mid-childhood. In addition, individual children demonstrated markedly different developmental trajectories in movement-related brain activity, suggesting that individual differences need to be taken into account when studying motor development across age groups.

Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation.

AIM: To report clinical outcomes and evidence of corneal innervation in patients with neurotrophic keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory nerves from the face. METHODS: Patients undergoing MICN at The Hospital for Sick Children, Toronto, Canada were prospectively recruited. Data on central corneal sensation (CCS, measured with Cochet-Bonnet aesthesiometer), best-corrected visual acuity (BCVA) and corneal epithelial integrity were collected. In four patients who subsequently underwent keratoplasty, immunohistochemical analysis was performed on the corneal explants. One patient underwent magnetoencephalography (MEG) after MICN to characterise the neurophysiological pathways involved. RESULTS: Between November 2012 and February 2017, 19 eyes of 16 patients underwent MICN. Mean follow-up was 24.0±16.1 months (range, 6-53). Mean CCS significantly improved from 0.8±2.5 mm to 49.7±15.5 mm at final follow-up (p<0.001). Mean BCVA remained stable, and the number of episodes of corneal epithelial defects after MICN was significantly reduced compared with the year leading up to the procedure (21% vs 89%, respectively; p<0.0001). In the four eyes that underwent keratoplasties after MICN, all transplants fully re-epithelialised and regained sensation subsequently. Immunohistochemistry of the corneal explants demonstrated evidence of corneal reinnervation. In one patient who was 8 months after MICN, novel neuroactivity was detected on MEG in the ipsilateral somatosensory cortex on mechanical stimulation of the reinnervated cornea. CONCLUSIONS: By providing an alternative source of innervation, MICN improves corneal sensation and stabilises the corneal epithelium, permitting optical keratoplasty for patients with NK-related corneal opacity.

BrainWave: A Matlab Toolbox for Beamformer Source Analysis of MEG Data.

BrainWave is an easy-to-use Matlab toolbox for the analysis of magnetoencephalography data. It provides a graphical user interface for performing minimum-variance beamforming analysis with rapid and interactive visualization of evoked and induced brain activity. This article provides an overview of the main features of BrainWave with a step-by-step demonstration of how to proceed from raw experimental data to group source images and time series analyses. This includes data selection and pre-processing, magnetic resonance image co-registration and normalization procedures, and the generation of volumetric (whole-brain) or cortical surface based source images, and corresponding source time series as virtual sensor waveforms and their time-frequency representations. We illustrate these steps using example data from a recently published study on response inhibition (Isabella et al., 2015) using the sustained attention to response task paradigm in 12 healthy adult participants. In this task participants were required to press a button with their right index finger to a rapidly presented series of numerical digits and withhold their response to an infrequently presented target digit. This paradigm elicited movement-locked brain responses, as well as task-related modulation of brain rhythmic activity in different frequency bands (e.g., theta, beta, and gamma), and is used to illustrate two different types of source reconstruction implemented in the BrainWave toolbox: (1) event-related beamforming of averaged brain responses and (2) beamformer analysis of modulation of rhythmic brain activity using the synthetic aperture magnetometry algorithm. We also demonstrate the ability to generate group contrast images between different response types, using the example of frontal theta activation patterns during error responses (failure to withhold on target trials). BrainWave is free academic software available for download at http://cheynelab.utoronto.ca/brainwave along with supporting software and documentation. The development of the BrainWave toolbox was supported by grants from the Canadian Institutes of Health Research, the National Research and Engineering Research Council of Canada, and the Ontario Brain Institute.

A preliminary study on the neural oscillatory characteristics of motor preparation prior to dysfluent and fluent utterances in adults who stutter.

PURPOSE: Recent literature on speech production in adults who stutter (AWS) has begun to investigate the neural mechanisms characterizing speech-motor preparation prior to speech onset. Compelling evidence has suggested that stuttering is associated with atypical processing within cortical and sub-cortical motor networks, particularly in the beta frequency range, that is effective before speech production even begins. Due to low stuttering frequency in experimental settings, however, the literature has so far predominantly reported on fluent speech production in AWS. Consequently, we have limited understanding of the way in which fluent speech processing in AWS is disturbed leading to a dysfluency. This preliminary study aims to characterize neural motor preparation prior to stuttered utterances in AWS. METHODS: Eight AWS participated in the study. A total of 336 stuttered utterances were compared to the participants' own fluent utterance productions. Beta oscillatory activity was analyzed with magnetoencephalography (MEG) and localized using minimum-variance beamforming. RESULTS: Preparation for speech production induced beta suppression in the bilateral premotor and motor cortex prior to speech onset. Although the data revealed some interesting trends, no significant differences between fluent and stuttered utterances were present. This may be due to a relatively low and variable number of stuttered trials analyzed in individual subjects. CONCLUSION: While the lack of significant differences may have resulted from the relatively low numbers of stuttered utterances across subjects, the observed trends demonstrated that the proposed methodology and experimental paradigm is a promising approach for future studies aiming to characterize differences between stuttered and fluent speech.

Sensorimotor Oscillations Prior to Speech Onset Reflect Altered Motor Networks in Adults Who Stutter.

Adults who stutter (AWS) have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG). Twelve AWS and 12 age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset) and speech execution (following speech onset). Compared to controls, AWS showed stronger beta (15-25 Hz) suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population.

An MEG-Compatible Electromagnetic-Tracking System for Monitoring Orofacial Kinematics.

We describe a novel motion-tracking system, called MASK (magnetoarticulography for the assessment of speech kinematics) designed to track detailed orofacial movements during magnetoencephalographic (MEG) measures of human brain activity. A three-dimensional electromagnetic-tracking method was employed using lightweight coils energized with high-frequency sinusoidal currents, creating magnetic dipoles that can be continuously localized by the MEG sensors. In addition to being compatible with commercial MEG devices, this system has advantages over optical or video methods in that it can record nonline-of-sight movements (e.g., tongue movements) and advantages over surface electromyographic recordings, which are prone to movement-related artifacts and signal crosstalk. Static and dynamic tracking accuracy was evaluated using calibration devices with fixed intercoil distances. MEG data were collected in two healthy adult volunteers to test feasibility of tracking movements during tongue and facial movement, and during overt speech. The MASK system was shown to have sufficient static and dynamic accuracy to track orofacial movements within the MEG helmet. We successfully acquired spatially precise kinematic information time-locked to brain activity with high temporal resolution. We demonstrated successful tracking of oromotor and speech movements together with brain activity using the MASK system. This novel technology will provide an innovative tool in support of research and clinical applications for individuals with speech and other oromotor disorders.

Complementary roles of cortical oscillations in automatic and controlled processing during rapid serial tasks.

Cognitive control may involve adjusting behaviour by inhibiting or altering habitual actions, requiring rapid communication between sensory, cognitive, and motor systems of the brain. Cognitive control may be achieved using top-down processing from frontal areas to inhibit prepared responses, likely mediated through frontal theta (4-8 Hz) oscillations. However there is conflicting evidence for mechanisms of response inhibition, where global and selective inhibition are either considered separate processes, or frontal areas maintain and execute goal-directed actions, including inhibition. In the current study we measured neuromagnetic oscillatory brain activity in twelve adults responding to rapidly presented visual cues. We used two tasks in the same subjects that required inhibition of a habitual "go" response. Presentation of infrequent "target" cues required subjects to completely inhibit responding (go/no-go task) or to perform an alternate response (go/switch task). Source analysis of oscillatory brain activity was compared for correct no-go and switch trials as well as error trials ("go" responses to targets). Frontal theta activity was similar in cortical location, amplitude and time course for correct no-go and switch responses reflecting an equivalent role in both global and selective response inhibition. Error-related frontal theta activity was also observed but was different in source location (errors vs correct, both tasks: p<0.005) and power (go/switch>go/no-go error, correct switch power, p=0.01). We additionally observed sensorimotor high gamma (60-90 Hz) activity accompanying motor responses, which was markedly stronger for correct switch and error responses compared with go responses, and was delayed for errors (p<0.01). These results suggest that gamma signals in the motor cortex may function to integrate inhibitory signals with sensorimotor processing, and may represent a mechanism for the overriding of habitual behaviours, as errors were predicted by a delay in gamma onset. This study supports a role for frontal areas in maintaining and executing goal-directed actions, and demonstrates that frontal theta activity and sensorimotor gamma oscillations have distinct yet complementary functional roles in monitoring and modifying habitual motor plans.

Movement-related neuromagnetic fields in preschool age children.

We examined sensorimotor brain activity associated with voluntary movements in preschool children using a customized pediatric magnetoencephalographic system. A videogame-like task was used to generate self-initiated right or left index finger movements in 17 healthy right-handed subjects (8 females, ages 3.2-4.8 years). We successfully identified spatiotemporal patterns of movement-related brain activity in 15/17 children using beamformer source analysis and surrogate MRI spatial normalization. Readiness fields in the contralateral sensorimotor cortex began ∼0.5 s prior to movement onset (motor field, MF), followed by transient movement-evoked fields (MEFs), similar to that observed during self-paced movements in adults, but slightly delayed and with inverted source polarities. We also observed modulation of mu (8-12 Hz) and beta (15-30 Hz) oscillations in sensorimotor cortex with movement, but with different timing and a stronger frequency band coupling compared to that observed in adults. Adult-like high-frequency (70-80 Hz) gamma bursts were detected at movement onset. All children showed activation of the right superior temporal gyrus that was independent of the side of movement, a response that has not been reported in adults. These results provide new insights into the development of movement-related brain function, for an age group in which no previous data exist. The results show that children under 5 years of age have markedly different patterns of movement-related brain activity in comparison to older children and adults, and indicate that significant maturational changes occur in the sensorimotor system between the preschool years and later childhood.