Resting State Functional Magnetic Resonance and Diffusion Tensor Imaging of Hemiplegic Cerebral Palsy Patients Treated with Constraint-Induced Movement Therapy: Predictors and Clinically Correlated Evidence of Neuroplasticity

Hemiplegic cerebral palsy is characterized by unilateral upper limb impairment and patients often compensate by performing most tasks with their unaffected arm. Constraint-induced movement therapy (CIMT) directly combats this learned non-use by casting the unaffected arm and forcing the patient to repetitively practice skills with the hemiplegic limb. Subjects with hemiplegic cerebral palsy were recruited from Holland Bloorview Kids Rehabilitation Hospital, Thames Valley Children’s Centre and McMaster Children’s Hospital. MRI acquisitions and clinical evaluations were collected at baseline, 1 and 6-months later. The case group participated in a CIMT camp after baseline evaluations and was compared to an untreated control group. Resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) acquisitions quantify global network organization and neural integrity, respectively, and found alterations in multiple resting state network connectivity patterns and significantly different fractional anisotropy and mean diffusivity in the affected corticospinal tract. Asymmetric baseline sensorimotor network organization was predictive of a positive and continuous functional response to CIMT. Clinically correlated network reorganization provides further evidence of neuroplastic mechanisms related to CIMT

Diffusion and Functional MRI of the Brain Following Sports-Related Impacts and Concussion

Concussion is a prevalent injury associated with contact sports, however the underlying brain changes associated with concussion remain poorly understood. Therefore it is critical to (a) understand the complex sequelae that underlie concussion, (b) when or if the brain recovers, and (c) if there are brain changes associated with contact sports in general. Advanced imaging techniques may be sensitive to changes that persist beyond relatively prompt symptom recovery and clearance to return to play. Resting state functional MRI (RS-fMRI) and diffusion tensor imaging (DTI) data was acquired on the 3T at Robarts Research Institute from healthy and concussed athletes from three separate cohorts. Healthy male hockey players were compared to longitudinal data acquired from concussed peers participating in Bantam-level hockey at 24-72 hours and 3 months after the injury. There were alterations in diffusion measures along multiple tracts with the largest significant decreases located along the superior longitudinal fasciculus at both times post-concussion. DTI tractography was used to relate diffusion changes with acute changes in functional connectivity. At 3 months post-concussion, network and regional connectivity analysis revealed compensatory functional hyperconnectivity patterns based on correlations with clinical symptoms and diffusion data. Longitudinal imaging data was acquired from concussed female rugby players post-concussion (at 24-72 hours, 3 and 6 months after injury) and compared to non-concussed teammates throughout the in- and off-season. Using a data-driven linked independent component analysis we observed acute disruptions in diffusion metrics inferiorly along the brainstem that recovered by 3 months post-concussion. However, we also observed long-lasting signatures that reflect co-varying alterations in brain microstructure and functional connectivity that related to the number of self-reported concussions. Based on these findings it appears that concussion initiates both acute and persistent changes to central white matter structures with subtle changes in functional connectivity. Given these findings, we acquired data from varsity-level female swimmers and rowers that were also scanned during the in- and off-season in order to directly compare with healthy rugby players and rule out the effects of high-level competitive exercise. We used accelerometers to quantify head rotational accelerations in a subset of the rowers and rugby players to confirm the number and magnitude of subclinical impacts. We quantified DTI alterations along major white matter tracts in contact compared to non-contact athletes that were in the opposite direction of our concussion findings. Diffusion changes within the genu and splenium of the corpus callosum were related to a history of concussion. Fluctuations in brainstem diffusion parameters between the in- and off-season as well as functional hyperconnectivity patterns within the default mode and medial visual networks were observed in contact athletes only. Together, these studies suggest that concussions result in an acute set of symptoms and microstructural brain changes. Despite quick resolution of symptoms, evidence of persistent axonal disruption exists at 3 and 6 months post-concussion and well-beyond symptomatic recovery. While functional hyperconnectivity may be one mechanism that allows the brain to function despite these disruptions, concussion may also compromise neuroprotective microstructural changes that protect the young, healthy brain throughout years of contact play. It remains to be seen if the brain changes associated with contact play and concussions are directly related to later risks of neurodegenerative processes

Resting State and Diffusion Neuroimaging Predictors of Clinical Improvements Following Constraint-Induced Movement Therapy in Children With Hemiplegic Cerebral Palsy.

The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = -0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with greater improvements in clinical scores. Higher mean diffusivity in the posterior limb of the internal capsule of the affect tract correlated significantly with improvements in the Jebsen-Taylor score (r = -0.83, P = .02). Children with more compromised networks and tracts improved the most following constraint therapy

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease

Previous studies have demonstrated altered brain activity in Alzheimer\u27s disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18 F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from F-18 FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid beta 1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD

Multiparametric MRI changes persist beyond recovery in concussed adolescent hockey players

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes. Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion. Results: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption. Conclusions: Changes persisted well after players’ clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated

Persistent post-concussion brain changes in adolescent hockey players

Changes continue to occur in a concussed brain even after standard clinical tests have returned to normal. Damage in the very long fibre tracks in the brain of concussed players can be detected up to three months after the concussion and after the individuals have been approved for return to athletics. It is also possible to detect ‘hyper-connectivity’ in the brain, suggesting the brain is still trying to compensate for the concussion.https://ir.lib.uwo.ca/brainscanresearchsummaries/1003/thumbnail.jp

Linked MRI signatures of the brain\u27s acute and persistent response to concussion in female varsity rugby players

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of the underlying neurobiology of concussion, but can also provide reliable information at the level of an individual athlete. In this study, we analyzed resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) within a cohort of female varsity rugby players (n = 52) through the in-and off-season, including concussed athletes (n = 21) who were studied longitudinally at three days, three months and six months after a diagnosed concussion. Linked components representing co-varying white matter microstructure and functional network connectivity characterized (a) the brain\u27s acute response to concussion and (b) persistent alterations beyond clinical recovery. Furthermore, we demonstrate that these long-term brain changes related to specific aspects of a concussion history and allowed us to monitor individual athletes before and longitudinally after a diagnosed concussion

Longitudinal changes of brain microstructure and function in nonconcussed female rugby players

ObjectiveTo longitudinally assess brain microstructure and function in female varsity athletes participating in contact and noncontact sports.MethodsConcussion-free female rugby players (n = 73) were compared to age-matched (ages 18-23) female swimmers and rowers (n = 31) during the in- and off-season. Diffusion and resting-state fMRI (rs-fMRI) measures were the primary outcomes. The Sports Concussion Assessment Tool and head impact accelerometers were used to monitor symptoms and impacts, respectively.ResultsWe found cross-sectional (contact vs noncontact) and longitudinal (in- vs off-season) changes in white matter diffusion measures and rs-fMRI network connectivity in concussion-free contact athletes relative to noncontact athletes. In particular, mean, axial, and radial diffusivities were increased with decreased fractional anisotropy in multiple white matter tracts of contact athletes accompanied with default mode and visual network hyperconnectivity (p \u3c 0.001). Longitudinal diffusion changes in the brainstem between the in- and off-season were observed for concussion-free contact athletes only, with progressive changes observed in a subset of athletes over multiple seasons. Axial diffusivity was significantly lower in the genu and splenium of the corpus callosum in those contact athletes with a history of concussion.ConclusionsTogether, these findings demonstrate longitudinal changes in the microstructure and function of the brain in otherwise healthy, asymptomatic athletes participating in contact sport. Further research to understand the long-term brain health and biological implications of these changes is required, in particular to what extent these changes reflect compensatory, reparative, or degenerative processes

Multiparametric MRI Changes Persist Beyond Recovery in Concussed Adolescent Hockey Players

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes. Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion. Results: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption. Conclusions: Changes persisted well after players’ clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated

Malignant hyperthermia

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%