Funded Studies
Objective/Rationale:
Freezing of Gait (FOG) in Parkinson’s disease occurs when a person’s feet become suddenly ‘frozen’ while walking or turning. FOG is a leading cause of falls, and responds poorly to current treatments. While the mechanisms underlying FOG are unknown, recent theories suggest that it is not merely a physical problem. Instead, it may reflect an overload of activity in the brain while performing cognitive (i.e. thinking) tasks. Researchers are now able to test these mechanisms using modern brain scanning techniques that capture brain activity.
Project Description:
Using functional magnetic resonance imaging (fMRI), this project will utilize a novel ‘virtual’ environment to elicit FOG. Whilst lying in the brain scanner, patients with PD will use foot pedals to ‘walk’ through a realistic three-dimensional environment that they will see on a small screen. The innovative virtual environment task has been developed by Dr. Simon Lewis and colleagues and will probe the cognitive processes that often provoke (e.g. sliding doors) or alleviate (e.g. striped floors) freezing episodes. It will also require patients to perform other tasks simultaneously which will trigger freezing while walking through the virtual environment. This project will evaluate a range of patients with PD both ‘on’ and ‘off’ their usual dopaminergic medications.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The results will enable researchers to determine the abnormal pattern of brain activation that relate to freezing and whether this differs in association with dopaminergic treatment. This is important since current treatments offer only limited symptom relief for freezing and there is an urgent need to develop better therapies. The results of this study will inform therapeutic approaches which target non-dopaminergic systems as well as those that target cognition specifically.
Anticipated Outcome:
This project will hopefully identify the abnormal pattern of brain activation that is responsible for FOG in PD. It is hypothesised that rather than simply reflecting a process that is related to gait, freezing episodes are in fact related to a breakdown in the circuitry that coordinates differing functional domains such as movement and thinking. Identifying the nature of these relationships will hopefully advance our understanding about freezing and lead to new directions for targeting therapy.
Progress Report
We are delighted to report that our study is making very good progress and is also leading to a number of interesting developments. Preliminary imaging work identified that we are able to show very distinct patterns of brain activity associated with different aspects of our virtual gait paradigm. Specifically, our initial results suggest that freezing is associated with both increased activity and deactivation occurring across differing regions of the brain. We suspect that these appearances reflect competing activity between the circuits that control various functions such as walking and thinking. When ‘overstretched’ this competition for brain resources results in a freezing episode. Although we still require more data collection and analysis, we are hopeful that the results of this study will lead to novel approaches in the treatment of patients suffering with freezing of gait. Our work has generated media interest and for those wanting more information there is an online vodcast at http://www.abc.net.au/catalyst/stories/2974717.htm.
Final Outcome
We are delighted to report that we have concluded all imaging studies that were proposed for this project. We are now busily analyzing the results of our data. We have already published the pattern of activation and deactivation seen in the brain of a single patient whilst performing our virtual reality task in the fMRI scanner. We are now preparing group data, which appears to confirm our initial findings where freezing episodes are associated with a distinct pattern of deactivation in the parts of the brain controlling movement of the lower limbs. We have also found a pattern of recruitment across regions of the brain that are not normally involved in movement but seem to be trying to find a ‘workaround’ to kick-start the feet back into action.
In addition to these findings, we believe that we have found different patterns of activation between patients with and without freezing as they are navigating narrow doorways in the virtual environment and when having to walk and think (dual-tasking). It is hoped that the results of this study will lead to novel approaches in the treatment of patients suffering with freezing of gait.
For those wanting more information http://www.abc.net.au/catalyst/stories/2974717.htm.
Presentations & Publications
Shine JM, Ward PB, Naismith SL, Pearson M, Lewis SJG. Utilising fMRI to identify the neural correlates of the freezing phenomenon in Parkinson’s Disease. J Clin Neurosci 2011; 18: 807-810.
Shine JM, Moore ST, Bolitho SJ, Morris TR, Dilda V, Naismith SL, Lewis SJG. Assessing the utility of Freezing of Gait Questionnaires in Parkinson's Disease. Parkinsonism Relat Disord 2011; 18: 25-9
Invited Speaker (full funding). Movement Disorders Research & Rehabilitation Centre. Waterloo, Canada June 2011. Virtual Reality: The Real Deal.
Plenary Session (no funding). Parkinson’s NSW ‘Stepping ahead with Parkinson’s Disease’. State Parliament, Sydney September 2010. Defrosting Parkinson’s Disease.
2010. A novel pathophysiological model of Freezing of Gait in Parkinson’s Disease.
Invited Speaker (full funding). Australasian Faculty of Rehabilitation Medicine (NSW). Sydney August 2010. Targeting gait disorder in Parkinson’s Disease.
Invited Speaker (full funding). Annual Sydney Neurology Movement Disorder Meeting. Sydney June 2010. Utilising functional MRI to identify the neural correlate of freezing.
Plenary Session (full funding). International Workshop on Freezing of Gait. Washington DC February 2010. A novel pathophysiological model of Freezing of Gait in Parkinson’s Disease.