A diagnosis of ALS is followed by relentless muscular weakness as the cortical motor system fails. This life limiting condition has no current effective therapy despite improved understanding of the genetic substrate.
The study investigates whether the pathophysiology of ALS is manifested in cortical activity during movement preparation and execution. Movement preparation, timing, and execution are associated with characteristic changes in on-going brain rhythms. We believe that these direct measures of cortical motor activity will be highly sensitive to neurodegeneration of motor circuits, and may provide very early markers of the condition, perhaps extending even into a pre-symptomatic phase of the illness. The inclusion of mutation carriers heavily predisposed to developing ALS in the medium term is a unique facet of our biomarker discovery project.
The search for more effective therapies against ALS will be hugely facilitated once we are better equipped to characterise the activity of the illness. MEG-based measures of cortical excitability and synaptic health should greatly contribute to existing neuroimaging and fluid based biomarkers in measuring the efficacy of novel interventions. The need for valid biomarkers is particularly pertinent in ALS given the vast inter-individual variation in rates of disease progression that complicates clinical trial design. Including an investigation of the neural basis for the cognitive deficits common to ALS is much needed given the pathological and genetic overlap between ALS and fronto-temporal dementia. Tests in development at the lab will be easily applicable to other disease groups and as such could add to the diagnostic framework for various neurodegerative disorders.
Malcolm Proudfoot’s doctoral research is funded by a Wellcome Trust Clinical Research Training Fellowship. The aim of his project is to improve detection of cortical dysfunction using non-invasive in-vivo techniques during tasks designed to explore vulnerable motor and cognitive domains. Malcolm is jointly supervised by Kia Nobre and Martin Turner, a pioneer in brain imaging of ALS and based at the Nuffield Department of Clinical Neurosciences.
Investigators and Collaborators
Clinical Research Fellow & Doctoral Student: Malcolm Proudfoot
Principal Investigators: Martin Turner (MRC Senior Clinician Scientist) and Kia Nobre.
Collaborators: Kevin Talbot (NDCN, Oxford), Michael Benatar (University of Miami), Gustavo Rohenkohl (ESI Frankfurt)
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