Browsing by Author "Kirton, Adam"

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    A Multimodal Approach to Understanding Motor Impairment in Developmental Coordination Disorder
    (2020-07-13) Grohs, Melody N.; Dewey, Deborah, M.; Dukelow, Sean; Lebel, Catherine; Kirton, Adam; Graham, Susan; Hands, Beth
    AbstractThe ability to learn, execute and adapt motor skills is fundamental to childhood development and promotes independence in daily living. Yet children with developmental coordination disorder (DCD), demonstrate difficulties acquiring and executing motor skills. DCD is a motor disorder that occurs in 5-6% of school-aged children. Motor impairment manifests as clumsy, slow and inaccurate motor performance adversely affecting the physical, academic and social outcomes of affected children. The pervasive negative impact of motor impairment on daily life in children with DCD, highlights the importance of early diagnosis and intervention. However, the motor deficits common among children with DCD remain unclear, making both screening and intervention difficult. There is a need for research with a priority focus on characterizing the motor deficits present in children with DCD. Evidence is growing, which suggests that poor motor performance in DCD is associated with motor control and motor learning deficits, however, findings are inconsistent across published studies. The current thesis used a three-pronged approach to investigate motor control and motor learning in children with diagnosed DCD, between the ages of 8 to 12 years: (1) two robotic behavioral tasks were employed to objectively quantify motor control abilities, (2) motor learning over five consecutive days of skill training and the potential of non-invasive brain stimulation to modulate rates of motor learning were explored, and (3) neuroimaging was used to investigate brain morphology of regions pertinent to motor control and motor learning. Spatial-temporal differences in reaching performance were observed in children with DCD, supporting the presence of motor control deficits. Preserved motor learning was also seen in the same sample of children. Non-invasive brain stimulation was unsuccessful in modulating the rate of motor learning. Finally, limited brain structural differences were observed in our DCD group compared to healthy controls. However, preliminary findings of reduced subcortical thalamic and pallidal volumes in our DCD group warrants further study, particularly given that these brain structures play critical roles in motor control and motor learning. Taken together, these findings suggest that the motor difficulties observed in children with DCD may be associated with compromised motor control systems.
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    An Innovative Ergometer For Measuring Neuromuscular Fatigue During And Immediately After Cycling Exercise
    (2017) Doyle-Baker, Douglas; Millet, Guillaume; MacIntosh, Brian; Murias, Juan; Temesi, John; Kirton, Adam
    During exercise, progressive changes in the central nervous system and muscles result in a contractile output that is less than anticipated, which is called neuromuscular fatigue. Many studies assessing fatigue from dynamic exercise in large muscle mass (e.g. cycling), have tended to delay measurements for 1-4 min after exercise cessation. This is problematic because recovery from exercise begins immediately after the activity has finished. This study aimed to determine the reliability of an innovative cycling ergometer that permits the start of measurement of fatigue within 1 s after exercise cessation, and compare these results to a traditional isometric chair ergometer. Twelve subjects participated in two data collection sessions, performing an incremental cycling test with intermittent isometric assessment of fatigue in the knee extensors with electrical nerve and transcranial magnetic stimulation. The innovative ergometer was found to be a reliable tool to assess neuromuscular fatigue during and immediately after cycling exercise.
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    Assessing Motor Adaptation Following Adolescent Sport-Related Concussion
    (2024-07-03) Stuart, Devon Walter; Dukelow, Sean; Cluff, Tyler; Kirton, Adam; Emery, Carolyn
    Concussion is a mild traumatic brain injury that is common for adolescents participating in sports. Sport-related concussion can be acquired through biomechanically diverse mechanisms of injury, leading to diverse damage to the brain that can result in cognitive, sensorimotor, and/or vestibular impairments. Currently there are no gold standard tools for clinicians to use when diagnosing, managing, and making clearance to play decisions following sport-related concussion. When examining individuals following suspected concussion and when making clearance decisions to play, we postulated that an assessment task that engages distributed, global brain networks to capture concussion-related neurological impairments would be useful. Motor adaptation is a brain function important for sport participation that requires engagement of sensory, motor, cognitive, and association regions of the brain, leading us test this brain function. This thesis examined motor adaptation impairments in adolescents at two timepoints: within 10 days postinjury (Experiment 1), and after obtaining medical clearance to return to sports (Experiment 2). Group level differences in all tested task parameters were seen within 10 days of sport-related concussion, with approximately one-in-four participants exhibiting overall impairments in motor adaptation. When medical clearance to return to play was granted, group level differences were no longer seen compared to healthy controls. However, approximately one-in-four participants who were medically cleared exhibited overall impairments in motor adaptation. Taken together, our results suggest that motor adaptation may be a valuable brain function to assess during the clinical management of sport-related concussion, especially given the relevance of motor adaptation within sport. Further, robotic tools were shown to be capable of detecting subtle neurological deficits after sport-related concussion.
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    Assessment of bilateral motor skills and visuospatial attention in children with perinatal stroke using a robotic object hitting task
    (2020-02-13) Hawe, Rachel L; Kuczynski, Andrea M; Kirton, Adam; Dukelow, Sean P
    Abstract Background While motor deficits are the hallmark of hemiparetic cerebral palsy, children may also experience impairments in visuospatial attention that interfere with participation in complex activities, including sports or driving. In this study, we used a robotic object hitting task to assess bilateral sensorimotor control and visuospatial skills in children with hemiparesis due to perinatal arterial ischemic stroke (AIS) or periventricular venous infarct (PVI). We hypothesized that performance would be impaired bilaterally and be related to motor behavior and clinical assessment of visuospatial attention. Methods Forty-nine children with perinatal stroke and hemiparetic cerebral palsy and 155 typically developing (TD) children participated in the study. Participants performed a bilateral object hitting task using the KINARM Exoskeleton Robot, in which they used virtual paddles at their fingertips to hit balls that fell from the top of the screen with increasing speed and frequency over 2.3 min. We quantified performance across 13 parameters including number of balls hit with each hand, movement speed and area, biases between hands, and spatial biases. We determined normative ranges of performance accounting for age by fitting 95% prediction bands to the TD children. We compared parameters between TD, AIS, and PVI groups using ANCOVAs accounting for age effects. Lastly, we performed regression analysis between robotic and clinical measures. Results The majority of children with perinatal stroke hit fewer balls with their affected arm compared to their typically developing peers. We also found deficits with the ipsilesional (“unaffected”) arm. Children with AIS had greater impairments than PVI. Despite hitting fewer balls, we only identified 18% of children as impaired in hand speed or movement area. Performance on the Behavioral Inattention Test accounted for 21–32% of the variance in number of balls hit with the unaffected hand. Conclusions Children with perinatal stroke-induced hemiparetic cerebral palsy may have complex bilateral deficits reflecting a combination of impairments in motor skill and visuospatial attention. Clinical assessments and interventions should address the interplay between motor and visuospatial skills.
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    Bilateral actigraphic quantification of upper extremity movement in hemiparetic children with perinatal stroke: a case control study
    (2021-12-16) Hollis, Asha; Cole, Lauran; Zewdie, Ephrem; Metzler, Megan J.; Kirton, Adam
    Abstract Background Hemiparetic cerebral palsy impacts millions of people worldwide. Assessment of bilateral motor function in real life remains a major challenge. We evaluated quantification of upper extremity movement in hemiparetic children using bilateral actigraphy. We hypothesized that movement asymmetry correlates with standard motor outcome measures. Methods Hemiparetic and control participants wore bilateral wrist Actiwatch2 (Philips) for 48 h with movement counts recorded in 15-s intervals. The primary outcome was a novel statistic of movement asymmetry, the Actigraphic Movement Asymmetry Index (AMAI). Relationships between AMAI and standard motor outcomes (Assisting Hand Assessment, Melbourne Assessment, and Box and Block Test [BB]) were explored with Pearson or Spearman correlation. Results 30 stroke (mean 11 years 2 months (3 years 10 months); 13 female, 17 male) and 23 control (mean 11 years 1 month (4 years 5 months); 8 female, 15 male) were enrolled. Stroke participants demonstrated higher asymmetry. Correlations between AMAI and standard tests were moderate and strongest during sleep (BB: r = 0.68, p < 0.01). Conclusions Standard tests may not reflect the extent of movement asymmetry during daily life in hemiparetic children. Bilateral actigraphy may be a valuable complementary tool for measuring arm movement, potentially enabling improved evaluation of therapies with a focus on child participation.
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    Bilateral reaching deficits after unilateral perinatal ischemic stroke: a population-based case-control study
    (2018-08-17) Kuczynski, Andrea M; Kirton, Adam; Semrau, Jennifer A; Dukelow, Sean P
    Abstract Background Detailed kinematics of motor impairment of the contralesional (“affected”) and ipsilesional (“unaffected”) limbs in children with hemiparetic cerebral palsy are not well understood. We aimed to 1) quantify the kinematics of reaching in both arms of hemiparetic children with perinatal stroke using a robotic exoskeleton, and 2) assess the correlation of kinematic reaching parameters with clinical motor assessments. Methods This prospective, case-control study involved the Alberta Perinatal Stroke Project, a population-based research cohort, and the Foothills Medical Center Stroke Robotics Laboratory in Calgary, Alberta over a four year period. Prospective cases were collected through the Calgary Stroke Program and included term-born children with magnetic resonance imaging confirmed perinatal ischemic stroke and upper extremity deficits. Control participants were recruited from the community. Participants completed a visually guided reaching task in the KINARM robot with each arm separately, with 10 parameters quantifying motor function. Kinematic measures were compared to clinical assessments and stroke type. Results Fifty children with perinatal ischemic stroke (28 arterial, mean age: 12.5 ± 3.9 years; 22 venous, mean age: 11.5 ± 3.8 years) and upper extremity deficits were compared to healthy controls (n = 147, mean age: 12.7 ± 3.9 years). Perinatal stroke groups demonstrated contralesional motor impairments compared to controls when reaching out (arterial = 10/10, venous = 8/10), and back (arterial = 10/10, venous = 6/10) with largest errors in reaction time, initial direction error, movement length and time. Ipsilesional impairments were also found when reaching out (arterial = 7/10, venous = 1/10) and back (arterial = 6/10). The arterial group performed worse than venous on both contralesional and ipsilesional parameters. Contralesional reaching parameters showed modest correlations with clinical measures in the arterial group. Conclusions Robotic assessment of reaching behavior can quantify complex, upper limb dysfunction in children with perinatal ischemic stroke. The ipsilesional, “unaffected” limb is often abnormal and may be a target for therapeutic interventions in stroke-induced hemiparetic cerebral palsy.
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    Clinical Prediction of Perinatal Arterial Ischemic Stroke
    (2022-06) Srivastava, Ratika; Kirton, Adam; Hill, Michael D; Richer, Lawrence; Samuel, Susan; Hagel, Brent
    Perinatal stroke is a well-defined but heterogenous group of disorders involving a focal disruption of cerebral blood flow between 20 weeks gestation and 28 days of life. At a combined incidence of 1:1000 live births, stroke in the perinatal period is more common than at any other time in childhood. Morbidity of perinatal stroke is high, and it is the most common cause of hemiparetic cerebral palsy. Years living with disability are amplified with deficits lasting a lifetime. Perinatal arterial ischemic stroke (PAIS) is the most common type of perinatal stroke. Advances in neuroimaging have allowed for exceptional growth in stroke diagnosis. However, etiology is poorly understood. Many pregnancy, delivery, and fetal risk factors have been considered, but targeted treatment and prevention efforts are still not possible. This thesis reviewed perinatal stroke and developed a diagnostic risk prediction model for PAIS. Pathophysiology, strategies for diagnosis, investigations, management, and outcomes were broken down by perinatal stroke disease, with an additional focus on family mental health and active trials for acute intervention. A diagnostic prediction model was then developed using novel, multisource data and multivariable logistic regression. Clinical pregnancy, delivery, and neonatal risk factors were collected from four registries including the Alberta Perinatal Stroke Project, Canadian Cerebral Palsy Registry, International Pediatric Stroke Study, and Alberta Pregnancy Outcomes and Nutrition study. Variable selection was based on peer-reviewed literature. The final model included nine clinical factors – maternal age, tobacco exposure, substance exposure, pre-eclampsia, chorioamnionitis, intrapartum maternal fever, emergency c-section, low 5-minute Apgar score, and male sex – to predict the risk of PAIS in a term neonate with good discrimination between cases and controls (C-statistic 0.73). This work highlights the lifelong effects of perinatal stroke on patients and families, and the potential for early perinatal stroke diagnosis. Findings suggest that clinical prediction and early, accurate diagnosis of PAIS may be possible using common clinical variables. Future research is needed to optimize risk prediction by better understanding perinatal stroke pathophysiology, including the role of the placenta, and identifying high-risk groups.
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    Clinician awareness of brain computer interfaces: a Canadian national survey
    (2020-01-06) Letourneau, Sasha; Zewdie, Ephrem T; Jadavji, Zeanna; Andersen, John; Burkholder, Lee M; Kirton, Adam
    Abstract Background Individuals with severe neurological disabilities but preserved cognition, including children, are often precluded from connecting with their environments. Brain computer interfaces (BCI) are a potential solution where advancing technologies create new clinical opportunities. We evaluated clinician awareness as a modifiable barrier to progress and identified eligible populations. Methods We executed a national, population-based, cross-sectional survey of physician specialists caring for persons with severe disability. An evidence- and experience-based survey had three themes: clinician BCI knowledge, eligible populations, and potential impact. A BCI knowledge index was created and scored. Canadian adult and pediatric neurologists, physiatrists and a subset of developmental pediatricians were contacted. Secure, web-based software administered the survey via email with online data collection. Results Of 922 valid emails (664 neurologists, 253 physiatrists), 137 (15%) responded. One third estimated that ≥10% of their patients had severe neurological disability with cognitive capacity. BCI knowledge scores were low with > 40% identifying as less than “vaguely aware” and only 15% as “somewhat familiar” or better. Knowledge did not differ across specialties. Only 6 physicians (4%) had patients using BCI. Communication and wheelchair control rated highest for potentially improving quality of life. Most (81%) felt BCI had high potential to improve quality of life. Estimates suggested that > 13,000 Canadians (36 M population) might benefit from BCI technologies. Conclusions Despite high potential and thousands of patients who might benefit, BCI awareness among clinicians caring for disabled persons is poor. Further, functional priorities for BCI applications may differ between medical professionals and potential BCI users, perhaps reflecting that clinicians possess a less accurate understanding of the desires and needs of potential end-users. Improving knowledge and engaging both clinicians and patients could facilitate BCI program development to improve patient outcomes.
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    Cortical Excitability after Mild Traumatic Brain Injury in Children
    (2015-12-04) Seeger, Trevor; Barlow, Karen; Kirton, Adam; Dunn, Jeff; Gallagher, Clare; Esser, Michael
    Introduction: Mild traumatic brain injury is frequently complicated by post-concussive syndrome. It is unknown why these symptoms persist, but recent research suggests that cortical excitability may play a role. Objectives: To determine if cortical excitability is different in pediatric mTBI, and if it correlates with symptom persistence. Methods:This was a cross-sectional controlled cohort study. Cortical excitability was measured using a variety of TMS paradigms in children with (symptomatic) and without (asymptomatic) persistent symptoms at one month post injury. The primary outcome measure was the corticalsilent period (cSP) (thought to represent GABAergic inhibition). Results: 57 children with mTBI (44% male; age 14.23 (SD:2.49)) and 28 controls were compared. cSP was similar between groups (F(2, 70)=0.53, p=0.591). There were no other significant group differences in cortical excitability. Conclusions: TMS was well tolerated in children with mTBI. Cortical excitability is similar to normal children at one-month following the injury.
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    Cortical excitability after pediatric mild traumatic brain injury
    (Elsevier, 2016-11-19) Seeger, Trevor A.; Kirton, Adam; Esser, Michael J.; Gallagher, Clare; Dunn, Jeff F.; Zewdie, Ephrem Takele; Damji, Omar; Ciechanski, Patrick; Barlow, Karen M.
    Introduction: Mild traumatic brain injury (mTBI) outcomes are variable, and 10e15% may suffer from prolonged symptoms beyond 3 months that impair the child's return to normal activities. Neurophysiological mechanisms of mTBI are incompletely understood, particularly in children, but alterations in cortical excitability have been proposed to underlie post-concussion syndrome. Improved understanding is required to advance interventions and improve outcomes. Objective/Hypothesis: To determine if cortical excitability is altered in children with mTBI, and its association with clinical symptoms. Methods: This was a cross-sectional controlled cohort study. School-aged children (8e18 years) with mTBI were compared to healthy controls. Cortical excitability was measured using multiple TMS paradigms in children with (symptomatic) and without (recovered) persistent symptoms one-month post-injury. Primary outcome was the cortical silent period (cSP), a potential neurophysiological biomarker of GABAergic inhibition. Secondary outcomes included additional TMS neurophysiology, safety and tolerability. Associations between neurophysiology parameters and clinical symptoms were evaluated. Results: Fifty-three children with mTBI (55% male; mean age 14.1 SD: 2.4 years; 35 symptomatic and 27 asymptomatic participants) and 28 controls (46% male; mean age 14.3 SD: 3.1 years) were enrolled. cSP duration was similar between groups (F (2, 73) ¼ 0.55, p ¼ 0.582). Log10 long interval intracortical inhibition (LICI) was reduced in symptomatic participants compared to healthy controls (F (2, 59) ¼ 3.83, p ¼ 0.027). Procedures were well tolerated with no serious adverse events. Conclusions: TMS measures of cortical excitability are altered at one month in children with mTBI. Long interval cortical inhibition is decreased in children who remain symptomatic at one month post-injury.
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    Corticospinal Tract Diffusion Tensor Imaging and Motor Function in Children following Perinatal Stroke
    (2013-01-08) Hodge, Jacquelyn; Kirton, Adam; Goodyear, Bradley
    Perinatal stroke causes most hemiplegic cerebral palsy. Understanding developmental motor plasticity after perinatal injury is key to developing new therapies. Diffusion tensor imaging (DTI) facilitates this by interrogating functional white matter tracts (e.g. corticospinal tract, CST) but is not well studied in perinatal stroke. Our aim was to quantify CST integrity following perinatal stroke with DTI, evaluating different methodologies and correlations to motor outcome. Twenty-six children (Alberta Perinatal Stroke Project) underwent standardized DTI. Fiber tracking across different CST sections and ROI analysis compared CST diffusion variable (FA/AD/RD/MD) ratios (lesioned/non-lesioned). Correlations with validated motor outcome measures (AHA, MA, PSOM) were sought. DTI quantified differences in all CST diffusion parameters. Decreased FA and increased RD in the lesioned CST demonstrated the most robust correlations with motor outcomes. Analysis of defined CST subtracts may offer advantages over traditional DTI techniques. CST DTI carries both clinical and research utility in perinatal stroke.
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    Designing strategies to support Implementation of iNtensive Therapy for Early Reach through PLAY (INTERPLAY) for young children with cerebral palsy: a study protocol
    (2024-06-18) Hilderley, Alicia; Cassidy, Christine; Reist-Asencio, Sandra; Tao, Chelsea; Tao, Stephen; McCoy, Susan; Vurrabindi, Divya; O’Grady, Kathleen; Herrero, Mia; Cambridge, Liz; Leverington, Eleanor; Micek, Victoria; Andersen, John; Fehlings, Darcy; Kirton, Adam
    Abstract Background Intensive manual therapy is important for improving lifelong upper limb motor outcomes for infants and toddlers with cerebral palsy. This play-based therapy is delivered by caregivers who are coached by occupational therapists. However, access to this therapy is very limited for Canadian children with cerebral palsy younger than two years old. This project aims to first identify barriers and facilitators and then design implementation strategies to support early intensive manual therapy delivery for infants and toddlers with cerebral palsy across Canada. Methods A mixed-methods sequential explanatory design will be used with four consecutive phases. The updated Consolidated Framework for Implementation Research will guide the study. Quantitative data will be collected from a survey in Phase One. Participants will be recruited from three groups: (1) Caregivers of children with cerebral palsy six years old and younger who are eligible for manual therapy; (2) occupational therapists who treat children with cerebral palsy; and (3) healthcare administrators or people responsible for managing pediatric occupational therapy programs. In Phase Two, quantitative data from the survey will be used to map to implementation strategies known to be effective at addressing the identified modifiable barriers and facilitators. Phase Three will collect qualitative data from semi-structured interviews for the purpose of explaining Phase One quantitative findings in greater depth, and for understanding the appropriateness of strategies identified in Phase Two. The participant recruitment strategy and interview guide content for Phase Three will be informed by results of Phase One. Phase Four will use a modified nominal group technique to refine and prioritize an implementation strategy toolbox. Results will be widely disseminated to knowledge users to provide them with tailorable strategies to increase delivery of early intensive manual interventions. Discussion This study will provide a comprehensive understanding of the barriers and facilitators to implementation of early intensive manual therapy for young children with cerebral palsy in Canada. A toolbox of evidence-based and tailorable implementation strategies will be disseminated nationally to support uptake of early intensive manual therapy into clinical practice for young children with cerebral palsy.
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    The Effect of Transcranial Direct Current Stimulation on GABA and Glx in Children During Motor Learning
    (2019-06-07) Nwaroh, Chidera; Harris, Ashley D.; Kirton, Adam; Bray, Signe L.; Condliffe, Elizabeth G.; Dunn, Jeffrey F.
    Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain activity. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity but there is little information about the underlying mechanisms. Additionally, studies have shown that tDCS can affect local levels of GABA and glutamate both of which are associated with skill acquisition and plasticity. This study aimed to quantify changes in GABA and Glx in response to 5 consecutive days of anodal tDCS or high definition tDCS targeting the M1 in children. Our results suggest HD-tDCS elicits a neurochemical response that is different from anodal tDCS despite resulting in similar motor enhancements. Additionally, we identified a relationship between left sensorimotor cortex GABA and improvements in motor performance. Overall, our results suggest that the developing brain responds differently to tDCS when compared to adult literature.
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    Effects of Transcranial Direct Current Stimulation on GABA and Glx in Children: A pilot study
    (Public Library of Science (PLoS), 2020-01-07) Nwaroh, Chidera; Giuffre, Adrianna; Cole, Lauran; Bell, Tiffany; Carlson, Helen L.; MacMaster, Frank P.; Kirton, Adam; Harris, Ashley D.
    Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS), it has been shown that tDCS can affect local levels of gamma-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right-handed children ages 12-18 years participated in five consecutive days of tDCS intervention (sham, a-tDCS or HD-tDCS) targeting the right M1 while training in a fine motor task (Purdue Pegboard Task) with their left hand. Glx and GABA were measured before and after the protocol (at day 5 and 6 weeks) using a PRESS and GABA-edited MEGA-PRESS MRS sequence in the sensorimotor cortices. Glx measured in the left sensorimotor cortex was higher in the HD-tDCS group compared to a-tDCS and sham at 6 weeks (p = 0.001). No changes in GABA were observed in either sensorimotor cortex at any time. These results suggest that neither a-tDCS or HD-tDCS locally affect GABA and Glx in the developing brain and therefore it may demonstrate different responses in adults.
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    Effects of Transcranial Direct-Current Stimulation on Motor Learning in the Developing Brain
    (2017) Ciechanski, Patrick; Kirton, Adam; Cheng, Adam; Johnston, Jamie; Teskey, Cam
    Transcranial direct-current stimulation (tDCS) is a form of non-invasive brain stimulation applied in both healthy and clinical populations. Application of weak current induces electric fields at the neuronal level, and may lead to behavioral effects such as enhanced motor learning when paired with training. Nearly all investigations to date have been completed in the adult brain, and fundamental studies are lacking in pediatrics, yet are required to advance and optimize tDCS application in this population. Additionally, given the ability of tDCS to enhance motor learning, translation to complex motor skill acquisition is necessary to define the full potential of tDCS. Here we investigated the effects of tDCS on motor learning in healthy children, with subsequent probing of neurophysiological changes underlying these behavioral changes using transcranial magnetic stimulation. Next, we compared tDCS-induced electric fields in the child, adolescent, and adult brain, using computational current modeling. Given the therapeutic potential of tDCS in pediatrics, we examined the safety and feasibility of tDCS application in childhood stroke. Finally, we examined the effects of tDCS on complex motor skill acquisition, including laparoscopic surgical and neurosurgical skills in medical trainees. Our findings suggest that tDCS can safely enhance motor learning in healthy children and young adults. Neurophysiological mechanisms underlying these changes appear to be variable. Current modeling suggests that children are exposed to substantially stronger electric fields compared to adults, possibly contributing to the complex neurophysiological changes seen with tDCS application in children. Despite inducing stronger electric fields, application of tDCS appears to be safe in children and adolescents. tDCS-enhanced motor learning may not be restricted to basic motor skills, but complex laparoscopic surgical skills, and neurosurgical tumor resection skills may be sensitive to enhancement as well. In summary, our findings suggest that tDCS application is safe in the developing brain, and capable of producing robust behavioral changes. These findings support the translation of tDCS to pediatric therapeutic investigations. Neurophysiological mechanisms of these changes require further investigation. Establishing the ability of tDCS to enhance surgical skill acquisition may counteract the current short-comings of surgical training, revolutionizing the field of medical education.
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    The Effects of Transcranial Direct-Current Stimulation on Motor Learning, Motor Maps, and Functional Networks in Children
    (2022-08) Giuffre, Adrianna; Kirton, Adam; Carlson, Helen; Kiss, Zelma; Cluff, Tyler
    Mapping the structure and function of the motor system in children informs our understanding of brain development, health, and disease. Neuronavigated robotic transcranial magnetic stimulation (TMS) is a state-of-the-art tool that can non-invasively explore primary motor cortex (M1) excitability and generate high-resolution motor maps of upper extremity muscles. However, fundamental studies are lacking in the developing brain. We propose a safe protocol, integrating methods capable of simultaneously exploring M1 modulation and TMS motor maps in typically developing children. Next, we investigated whether behavioural performance corresponds to TMS motor map outcomes and M1-excitability. We generated detailed bilateral motor maps of multiple hand muscles and observed hemispheric-specific relationships between M1-excitability, map outcomes, and motor performance. As most TMS mapping studies have reported variable results, we also determined the reliability of robotic TMS motor maps and specific outcomes across short- and long-term sessions. Our findings suggest that careful interpretation of mapping protocols and outcomes is required to interrogate M1 plasticity. M1 has become a central target to modulate plasticity for its critical role in motor control and learning. Transcranial direct current stimulation (tDCS) can non-invasively modulate M1-excitability in healthy and clinical populations. Primarily studied in adults, tDCS can enhance motor learning when paired with a motor task. However, the effects of tDCS may differ in the developing brain due to anatomical and maturational idiosyncrasies. High-definition tDCS (HD-tDCS) provides more focal targeting of cortical areas, leading to enhanced motor learning in adults, but is yet to be investigated in a pediatric population. Therefore, we aimed to determine the effects of tDCS and HD-tDCS on upper limb motor learning in typically developing children. We demonstrated that both forms of stimulation safely enhanced motor learning with long-term retention of effects. With a pressing need to determine the underlying mechanisms of such neuromodulation, we then applied our TMS mapping methods and advanced functional magnetic resonance imaging (fMRI) techniques to characterize the effects of tDCS-enhanced motor learning on motor network physiology. Alterations in motor maps and both inter-and intra-hemispheric functional motor networks were identified. We have advanced the understanding of motor system developmental and interventional plasticity in children.
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    Epidemiology of Perinatal Stroke
    (2021-06-18) Dunbar, Mary Jansen; Kirton, Adam; Hill, Michael; Coutts, Shelagh; Samuel, Susan
    Perinatal stroke is a collection of distinct clinicoradiographic syndromes resulting in injury to the developing brain between 20 weeks gestation and 28 days post-natal age. Perinatal stroke is the leading cause of hemiparetic cerebral palsy and also causes other adverse outcomes such as epilepsy and neurodevelopmental challenges, as well as significant economic burden and emotional burden for families. The birth prevalence was estimated to be between 1/1600 births and 1/3000 births depending on definitions and study methodology; however, no published study to date had evaluated all six subtypes of perinatal stroke birth prevalence to define their relative prevalence and other characteristics such as sex ratios and changes over time. Each subtype of perinatal stroke requires individual characterization of birth prevalence, risk factors and outcomes to better inform early diagnosis, treatment and prevention. Some subtypes of perinatal stroke such as neonatal arterial ischemic stroke have been well studied, while for others such as periventricular venous infarction (PVI), birth prevalence and risk factors remain unknown. In this thesis the birth prevalence of all six types of perinatal stroke was estimated using the Alberta Perinatal Stroke Project (APSP), a population-based registry of all types of perinatal stroke in Southern Alberta, Canada. We also compared retrospective methods using administrative data, and prospective methods using the APSP registry. Poisson regression was used to assess changes in annual birth prevalence over time. To further characterize PVI, a systematic review and individual patient data meta-analysis was conducted to consolidate data about antenatally-diagnosed germinal matrix intraventricular hemorrhage, which is believed to be the pathophysiology for PVI. Logistic regression was used to evaluate outcomes and co-occurring conditions. We found the highest estimated birth prevalence of perinatal stroke to date of 1/1100 births, which is a rate of one per day in Canada. In addition, novel insights were determined regarding the relative proportions and sex proportions of the stroke subtypes, including the finding that males with arterial ischemic stroke are more likely than females to present in the perinatal period. Periventricular venous infarction was found to be the second most common subtype of perinatal stroke, and systematic review and individual patient data meta-analysis demonstrated that the grading system developed for delivered preterm infants is relevant to fetuses and that outcome may be additionally influenced by gestational age at birth. In addition, a variety of co-occurring conditions were identified. This thesis presents an estimated birth prevalence of perinatal stroke that is higher than previously thought and posits that it must be calculated as a sum of the perinatal stroke subtypes. Our results set the stage for exciting new studies to better understand the role of sex in neonatal seizures as a presentation of brain injury, as well as established the groundwork for case-control studies of risk factors in periventricular venous infarction. Increased knowledge of epidemiology and understanding of risk factors is crucial to develop strategies for early diagnosis, treatment and ideally prevention of perinatal stroke.
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    Examining Chronic Post-Stroke Aphasia Recovery Using Non-Invasive Brain Stimulation and Neuroimaging
    (2024-06-24) Low, Trevor A; Dukelow, Sean; Goodyear, Bradley; Kirton, Adam
    Aphasia, an impairment in language processing, affects approximately one-third of stroke survivors immediately after stroke and up to 50% will have long-term impairments. Rehabilitation of aphasia at the chronic phase is possible, though outcomes are variable and often minimal. Novel therapeutic approaches and an increased understanding of the neurobiology supporting recovery are needed. Chapter Two assessed the safety and feasibility of combining repetitive transcranial magnetic stimulation (rTMS) with high-intensity Multi-Modality Aphasia Therapy (M-MAT) in chronic post-stroke aphasia (n=20). This novel combination therapy was determined to be feasible and safe in chronic post-stroke aphasia. On the basis of all participants benefiting from M-MAT regardless of rTMS allocation, we used resting-state fMRI (Chapter Three) and diffusion-weighted MRI (Chapter Four) to examine functional and structural connectivity associated with changes in speech production. In individuals that made positive, significant changes in naming, pre-treatment functional and structural connectivity of left hemisphere temporal and parietal language regions were associated with greater treatment-related improvement in naming. Additionally, naming improvements were associated with decreases in functional connectivity of bilateral posterior temporoparietal regions with frontoparietal, sensorimotor and visual networks at post-treatment. In Chapter Five, we conducted a randomized controlled trial investigating the efficacy of rTMS plus M-MAT on aphasia severity in a larger cohort of chronic stroke participants (n=43). Delivery of rTMS combined with M-MAT resulted in significant supplemental improvements in aphasia severity compared to sham plus M-MAT at follow-up. This demonstrates that rTMS is a promising adjuvant therapy for M-MAT in chronic stroke. Chapter Six investigated the neural basis of adjuvant rTMS effects using overt naming fMRI. Participants who received rTMS with M-MAT demonstrated dynamic functional reorganization over time, resulting in increased recruitment of left hemisphere perisylvian and temporoparietal regions at 15 weeks compared to sham. These data demonstrate potential mechanisms for the behavioural improvements observed following rTMS plus M-MAT. This thesis provides evidence to support the efficacy of rTMS plus M-MAT for improving chronic post-stroke aphasia. In addition, this thesis advances our understanding of the structural and functional brain architecture that supports aphasia recovery. These behavioural and neuroimaging results are important for the advancement of post-stroke aphasia rehabilitation.
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    Examining the Rate of Recovery Across Movement Parameters Post-Stroke
    (2023-06) Cowan-Nelson, Emilee; Dukelow, Sean; Kirton, Adam; Demchuk, Andrew
    Stroke is one of the leading causes of disability worldwide. Following a stroke, many individuals suffer from upper limb motor impairment which can hinder their ability to complete daily tasks. It has been suggested that recovery of the upper limb is greatest within the first three months post-stroke, as measured by clinical scores, after which recovery reaches a plateau. Kinematic measures of motor recovery however suggest that recovery is not only greatest within the first six weeks post-stroke, but continues well beyond the suggested three month plateau. Further, data from our lab suggests that certain spatial and temporal movement parameters may show different patterns of recovery. The purpose of this thesis was to examine patterns of spatial and temporal motor recovery in subacute stroke survivors using a Kinarm robotic exoskeleton. Chapter Two of this thesis is comprised of a manuscript which details this project. Our results suggest that the greatest recovery in spatial and temporal parameters of movement occurs within 1- to 6-weeks post-stroke. Additionally, spatial and temporal movement parameters appear to follow similar patterns of motor recovery overall. With a better understanding of motor recovery post-stroke, therapists can tailor rehabilitation practices to ensure movement parameters are targeted at the appropriate time, allowing patients to achieve better recovery outcomes.
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    Exploring Functional Connectivity Among Adults with Persistent Post-Concussion Syndrome Using Functional Near Infrared Spectroscopy
    (2022-12-01) du Plessis, Sané; Debert, Chantel; Kirton, Adam; Dunn, Jeffrey
    Approximately one third of all concussions lead to persistent post concussion syndrome (PPCS). Functional near infrared spectroscopy (fNIRS) is a non-invasive imaging technique that measures the differences in the absorption of local oxy- and deoxyhemoglobin in the brain. The changes in cerebral tissue oxygenation are then used to monitor brain activity. fNIRS has demonstrated comparability to fMRI for reliably detecting changes in cerebral vascular reactivity and may provide insight into the pathophysiology of PPCS. The aim of this study was to compare the hemodynamic response of participants with PPCS to symptom burden using fNIRS in frontal and motor brain regions. Thirty-four adults (18-65) with PPCS (>3 months - 5 years) were asked to complete a series of clinical questionnaires including the Rivermead Post-Concussion Symptom Questionnaire (RPQ) to assess symptom burden and complete a resting task, motor task, and working memory task during fNIRS assessments. Demographic information including age, sex, education level and employment status, and participant characteristics including concussion history, past medical history, medication use, and family medical history were also collected. A multiple regression analysis was conducted to assess the relationship between functional connectivity measures and symptom severity scores after consideration for age, sex, and time since injury. RPQ scores were not found to be significantly related to connectivity measures for oxy- (β = -0.02, p = 0.90) or deoxyhemoglobin (β = 0.31, p = 0.08) between the right and left dorsolateral prefrontal cortex (DLPFC) during the working memory task. However, increased deoxyhemoglobin functional connectivity measures between the left and right DLPFC during the working memory task were significantly related to higher depression scores (β = 0.44, p < 0.05), anxiety scores (β = 0.54, p < 0.05), somatoform symptom scores (β = 0.43, p < 0.05), and post-traumatic stress injury scores (β = 0.43, p < 0.05). Furthermore, the relationship between working memory fNIRS connectivity values and RPQ was further explored by analyzing the relationship between specific symptoms and fNIRS outcomes. Several RPQ items were significantly related to task-evoked deoxyhemoglobin functional connectivity scores between the left and right DLPFC including “feeling depressed or tearful” (β = 0.41, p < 0.05), “poor memory or forgetting” (β = 0.34, p < 0.05), and “difficulty concentrating” (β = 0.34, p < 0.05). The preliminary data and results from this study may contribute to a better understanding of brain function and specific symptoms in patients with PPCS.