Krembil Neuroscience Center

Toronto, Canada

Krembil Neuroscience Center

Toronto, Canada
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Esopenko C.,Rotman Research Institute | Esopenko C.,Rutgers University | Chow T.W.,University of Southern California | Tartaglia M.C.,University of Toronto | And 12 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2017

Background and Objective The relationship between repeated concussions and neurodegenerative disease has received significant attention, particularly research in postmortem samples. Our objective was to characterise retired professional ice hockey players' cognitive and psychosocial functioning in relation to concussion exposure and apolipoprotein μ 4 status. Methods Alumni athletes (N=33, aged 34-71â €..years) and an age-matched sample of comparison participants (N=18) were administered measures of cognitive function and questionnaires concerning psychosocial and psychiatric functioning. Results No significant group differences were found on neuropsychological measures of speeded attention, verbal memory or visuospatial functions, nor were significant differences observed on computerised measures of response speed, inhibitory control and visuospatial problem solving. Reliable group differences in cognitive performance were observed on tests of executive and intellectual function; performance on these measures was associated with concussion exposure. Group differences were observed for cognitive, affective and behavioural impairment on psychosocial questionnaires and psychiatric diagnoses. There was no evidence of differential effects associated with age in the alumni athletes. Possession of an apolipoprotein 4 allele was associated with increased endorsement of psychiatric complaints, but not with objective cognitive performance. Conclusions We found only subtle objective cognitive impairment in alumni athletes in the context of high subjective complaints and psychiatric impairment. Apolipoprotein 4 status related to psychiatric, but not cognitive status. These findings provide benchmarks for the degree of cognitive and behavioural impairment in retired professional athletes and a point of comparison for future neuroimaging and longitudinal studies. © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-And-licensing/.


Kidane B.,University of Western Ontario | Gandhi R.,Toronto Western Hospital | Gandhi R.,University of Toronto | Sarro A.,Toronto Western Hospital | And 5 more authors.
Canadian Family Physician | Year: 2011

Objective: To assess the concerns of adult patients with spine-related complaints during the period between referral to and consultation with a spine surgeon. Design: Prospective survey. Setting: Toronto, Ont. Participants: A total of 338 consecutive, nonemergent patients before consultation with a single spine surgeon over a 5-month period. Main outcome measures: Patient concerns, effect of referral to a spine surgeon, and effect of waiting to see a spine surgeon. Results: The issues patients reported to be most concerning were ongoing pain (45.6% rated this as most concerning), loss of function (23.4%), need for surgery (12.1%), and permanence of the condition (9.6%). Regression analysis demonstrated that older age was an independent predictor of increased level of concern regarding pain (P = .01) and disability (P = .04). Forty-seven percent of all patients listed the need for surgery among their top 3 concerns. Mere referral to a spine surgeon (P = .03) was an independent predictor of increased concern regarding the need for surgery. Sex, diagnosis, surgical candidacy, and actual wait time were not predictive of increased concerns. Patients reported family physicians to be their most influential information source regarding spinal conditions. Conclusion: Timely provision of more specific information regarding the benign and non-surgical nature of most degenerative spinal conditions might substantially reduce patients' exaggerated concerns regarding the probability of surgery for a considerable number of patients referred to spine surgeons.


McGinn R.J.,Western Research Institute | McGinn R.J.,University of Toronto | Valiante T.A.,Western Research Institute | Valiante T.A.,Krembil Neuroscience Center | Valiante T.A.,University of Toronto
Journal of Neuroscience | Year: 2014

One of the striking manifestations of neuronal population activity is that of rhythmic oscillations in the local field potential. It is thought that such oscillatory patterns, including phase-amplitude coupling (PAC) and inter-regional synchrony, may represent forms of local and long-range cortical computations, respectively. Although it has been speculated that these two oscillatory patterns are functionally related, and bind disparate cortical assemblies to one another at different timescales, there is little direct evidence to support this hypothesis. We have demonstrated recently that theta to high-gamma PAC and interlaminar phase coherence at theta frequencies can be generated in human cortical slices maintained in vitro. Here we show that not only do such oscillatory patterns exist within human temporal neocortex, but that the strength of one is related to the strength of the other. We demonstrate that at theta frequencies, metrics of temporal synchrony between superficial and deep cortical laminae (phase-dependent power correlations, and phase coherence) are correlated to the magnitude of intralaminar PAC between theta and high-gamma. Specifically, our results suggest that interlaminar communication within human temporal neocortex and local laminar excitability are linked to one another through a dependence mediated by theta oscillations. More generally, our results provide evidence for the hypothesis that theta oscillations may coordinate inter-areal excitability in the human brain. © 2014 the authors.


Prescott I.A.,University of Toronto | Liu L.D.,University of Toronto | Dostrovsky J.O.,University of Toronto | Hodaie M.,Western Research Institute | And 6 more authors.
Neurobiology of Disease | Year: 2014

Parkinson's disease (PD), characterized by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease which produces bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (L-Dopa) is the most effective treatment for the amelioration of PD signs and symptoms, but long-term administration can lead to disabling motor fluctuations and L-Dopa-induced dyskinesias. In animal models of PD, a form of plasticity called depotentiation, or the reversal of previous potentiation, is selectively lost after the development of dyskinetic movements following L-Dopa treatment. We investigated whether low frequency stimulation (LFS) in the globus pallidus internus (GPi) and substantia nigra pars reticulata (SNr) could induce depotentiation at synapses that had already undergone high frequency stimulation (HFS)-induced potentiation. To do so, we measured the field potentials (fEPs) evoked by stimulation from a nearby microelectrode in 28 patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN) or GPi. We found that GPi and SNr synapses in patients with less severe dyskinesia underwent greater depotentiation following LFS than in patients with more severe dyskinesia. This demonstration of impaired depotentiation in basal ganglia output nuclei in PD patients with dyskinesia is an important validation of animal models of levodopa-induced dyskinesia. The ability of a synapse to reverse previous potentiation may be crucial to the normal function of the BG, perhaps by preventing saturation of the storage capacity required in motor learning and optimal motor function. Loss of this ability at the output nuclei may underlie, or contribute to the cellular basis of dyskinetic movements. © 2014 Elsevier Inc.


Roberts J.L.,Bangor University | Anderson N.D.,University of Toronto | Anderson N.D.,Rotman Research Institute | Guild E.,Krembil Neuroscience Center | And 3 more authors.
Neuropsychological Rehabilitation | Year: 2016

The aim of this study was to explore whether errorless learning leads to better outcomes than errorful learning in people with amnestic mild cognitive impairment (MCI), and to examine whether accuracy in error recognition relates to any observed benefit of errorless over errorful learning. Nineteen participants with a clinical diagnosis of amnestic MCI were recruited. A word-list learning task was used and learning was assessed by free recall, cued recall and recognition tasks. Errorless learning was significantly superior to errorful learning for both free recall and cued recall. The benefits of errorless learning were less marked in participants with better error recognition ability. Errorless learning methods are likely to prove more effective than errorful methods for those people with MCI whose ability to monitor and detect their own errors is impaired. © 2016 Informa UK Limited, trading as Taylor & Francis Group


Fehlings M.G.,Krembil Neuroscience Center | Nater A.,Toronto Western Hospital
Neurosurgery Clinics of North America | Year: 2015

Although it is intuitive that any neurosurgeon would seek to consistently apply the best available evidence to patient management, the application of evidence-based medicine (EBM) principles and clinical practice guidelines (CPGs) remains variable. This article reviews the origin and process of EBM, and the development, assessment, and applicability of EBM and CPGs in neurosurgical care, aiming to demonstrate that CPGs are one of the valid available options that exist to improve quality of care. CPGs are not intended to define the standard of care but to compile dynamic advisory statements, which need to be updated as new evidence emerges. © 2015 Elsevier Inc.


Ni Z.,Krembil Neuroscience Center | Ni Z.,University of Toronto | Muller-Dahlhaus F.,Goethe University Frankfurt | Chen R.,Krembil Neuroscience Center | And 2 more authors.
Brain Stimulation | Year: 2011

Transcranial magnetic stimulation (TMS) is a widely used brain stimulation technique that allows noninvasive examination of different excitatory and inhibitory circuits at the systems level in the intact human brain. In recent years, considerable knowledge has been accumulated about the physiology of several of these facilitatory and inhibitory processes individually. However, activity in the corresponding neural circuits is not independent of each other. This paper reviews the experiments using triple-pulse TMS that are specifically designed to study interactions between intracortical circuits. These studies have provided evidence for a complex network of interconnected neural circuits within and across cerebral hemispheres. The current knowledge about the functional organization of this network, its pharmacology and functional implications for human motor control are discussed in detail. These findings have clinical relevance because specific interactions between neural circuits may be impaired in neurologic and psychiatric disorders. We conclude that triple-pulse TMS studies will help to integrate and better understand the physiologic processes involved in human motor behavior. © 2011 Elsevier Inc. All rights reserved.


PubMed | Krembil Neuroscience Center
Type: Journal Article | Journal: The European journal of neuroscience | Year: 2011

Changes in intracellular Ca(2+) play a key role in regulating gene expression and developmental changes in oligodendroglial precursor cells (OPCs). However, the mechanisms by which Ca(2+) influx in OPCs is controlled remains incompletely understood. Although there are several mechanisms that modulate Ca(2+) influx, in many systems the large-conductance, voltage- and Ca(2+) -activated K(+) channel (BK channel) plays an important role in regulating both membrane excitability and intracellular Ca(2+) levels. To date, the role of the BK channel in the regulation of intracellular Ca(2+) in oligodendroglial lineage cells is unknown. Here we investigated whether cells of the oligodendroglial lineage express BK channels and what potential role they play in regulation of Ca(2+) influx in these cells. In oligodendrocytes derived from differentiated adult neural precursor cells (NPCs, obtained from C57bl6 mice) we observed outward currents that were sensitive to the BK channel blocker iberiotoxin (IbTx). Further confirmation of the expression of the BK channel was obtained utilizing other blockers of the BK channel and by confocal immunofluoresence labelling of the BK channel on oligodendroglia. Using Fura-2AM to monitor intracellular Ca(2+) , it was observed that inhibition of the BK channel during glutamate-induced depolarization led to an additive increase in intracellular Ca(2+) levels. Electrophysiological difference currents demonstrated that the expression levels of the BK channel decrease with developmental age. This latter finding was further corroborated via RT-PCR and Western blot analysis. We conclude that the BK channel is involved in regulating Ca(2+) influx in OPCs, and may potentially play a role during differentiation of oligodendroglial lineage cells.


PubMed | Krembil Neuroscience Center and Toronto Western Hospital
Type: Journal Article | Journal: Neurosurgery clinics of North America | Year: 2015

Although it is intuitive that any neurosurgeon would seek to consistently apply the best available evidence to patient management, the application of evidence-based medicine (EBM) principles and clinical practice guidelines (CPGs) remains variable. This article reviews the origin and process of EBM, and the development, assessment, and applicability of EBM and CPGs in neurosurgical care, aiming to demonstrate that CPGs are one of the valid available options that exist to improve quality of care. CPGs are not intended to define the standard of care but to compile dynamic advisory statements, which need to be updated as new evidence emerges.


News Article | March 2, 2017
Site: www.eurekalert.org

Toronto - Researchers at Toronto Western Hospital's Canadian Concussion Centre (CCC) have discovered the presence of chronic traumatic encephalopathy (CTE) in the brain of a deceased patient with no known history of traumatic brain injury or concussion, the first known case of its kind. The case study, published in the International Journal of Pathology and Research and presented at the CCC's 5th annual symposium on Research on the Concussion Spectrum of Disorders, discusses the unexpected finding which resulted from an autopsy examining the brain of a patient with a seven-year history of clinically diagnosed amyotrophic lateral sclerosis (ALS) and motor neuron disease (MND), yet no history of head trauma or any participation in activities associated with risk of concussion, according to his family. "The finding of CTE in an individual who not only had no known head trauma, but also showed no signs of dementia or cognitive impairment and was high functioning mentally until his death, highlights that the cause of CTE might be more complex than we assume," says Dr. Lili-Naz Hazrati, neuropathologist with the CCC research team who conducted the autopsy. "So far, we have only seen this neurodegenerative disease in the brains of people with history of brain injury or multiple concussions, and we are not questioning that a relationship may exist between repetitive head trauma and brain degeneration," she continues. "But, at this point in time, we have more questions than answers about the definitive causes of CTE, and findings like these give us new directions to pursue and investigate." "Finding CTE in a patient without a history of concussion is an interesting development that opens up our understanding of this disease," says Dr. Charles Tator, Director of the CCC and a co-author of the case study. "As researchers, we need to go where the evidence takes us, and it now seems possible that CTE affects a wider range of people. The more we know about this disease, the more likely we'll be able to figure out how to treat it and perhaps eventually prevent it." To date, brain autopsies of cases where individuals reported suffering multiple concussions have yielded a wide range of results, including: no neuropathological changes in the brain, presence of CTE alone, presence of CTE and another neurodegenerative disease, or a non-CTE neurodegenerative disease only. The majority of brains studied by the CCC and other centres have come from donations made as a result of concern over symptoms -- usually of unexplained cognitive impairment -- displayed while the individual was alive, though not all of these cases resulted in findings of the CTE tauopathy in the brain. However, the referral of brains of symptomatic individuals who have a history of concussions increases the chances that some form of brain degeneration -- whether CTE or other -- would be present, which has potential to create a sample that isn't representative of the overall population. "Obviously brain trauma and repetitive brain trauma can result in cognitive impairment and possibly contribute to a neurodegenerative disease," says Dr. Hazrati. "But since we've seen cases of brains that experienced multiple concussions but don't have CTE, and now a brain with CTE but absence of any head trauma, there is indication that we should be cautious about labelling trauma as the only possible cause of CTE because it looks to be more complicated than that." The CCC comprises a group of 23 clinician and basic scientists, and is one of few research groups in the world to examine the entire spectrum of concussion disorders from acute injury to chronic illness including brain degeneration. The team harnesses the expertise of scientists and clinicians in brain injuries, imaging, genetics, neuropsychology, neurology, neurosurgery, neuropathology and clinical care at the KNC and other brain research facilities to further understanding of this common brain injury that can cause lasting disability. For more information please visit the CCC website The Krembil Neuroscience Centre (KNC), located at Toronto Western Hospital, is home to one of the largest combined clinical and research neurological facilities in North America. Since opening in 2001, KNC has been recognized as a world leader through its research achievements, education and exemplary patient care. The centre focuses on the advancement, detection and treatment of neurological diseases and specializes in movement disorders, dementias, stroke, spinal cord injury, blinding eye diseases, epilepsy and cancer-related conditions.

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