HD Brain-Train: Neuroplasticity as a Target to Improve Function in Huntington's Disease
Stand-By Time
Thursday, June 29, 2017: 12:45 PM - 2:45 PMSubmission No:
3733
Submission Type:
Abstract Submission
On Display:
Wednesday, June 28 & Thursday, June 29
Authors:
Marina Papoutsi1, Joerg Magerkurth2,3, Oliver Josephs3, Sophia Pepes1, Temitope Ibitoye1, Ralf Reilmann4, Douglas Langbehn5, Nikolaus Weiskopf6,3, Geraint Rees3,7, Sarah Tabrizi1
Institutions:
1Huntington's Disease Centre, University College London, London, United Kingdom, 2Birkbeck-UCL Centre for Neuroimaging, University College London, London, United Kingdom, 3Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom, 4George Huntington Institute & Dept. of Radiology, University of Muenster, Muenster, Germany, 5Carver College of Medicine, University of Iowa, Iowa, United States, 6Department of Neurophysics, Max Planck Institute for Human Cognition and Brain Sciences, Leipzig, Germany, 7Institute of Cognitive Neuroscience, University College London, London, United Kingdom
First Author:
Marina Papoutsi
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Lecture Information
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Huntington's Disease Centre, University College London
London, United Kingdom
Huntington's Disease Centre, University College London
London, United Kingdom
Introduction:
Real-time fMRI neurofeedback training is a novel approach that induces training-related neuroplasticity[10]. By providing participants with feedback of their own neural activity in a closed-loop experimental design, participants gradually learn to control their own brain activity, thereby inducing neural changes to target regions and their associated networks[1-3,5,7]. Neurological diseases or symptoms are associated with neuronal dysfunction. Therefore, methods to normalize neuronal function by inducing plasticity may improve symptoms or delay disease progression. For Huntington's disease (HD), an autosomal-dominant neurodegenerative disease affecting motor and cognitive function, regions affected by the disease show reduction of activity, loss of connectivity and atrophy that correlates with impairment[4,6,8,9]. An important question is therefore whether HD patients can learn to volitionally control the activity of affected regions, and what effect that would have on their cognitive and motor function.
Methods:
To answer this question, ten HD patients at early and pre-manifest (asymptomatic) stages of HD were recruited and completed an intensive real-time fMRI neurofeedback training paradigm. Patients were trained to volitionally increase BOLD fMRI signals from the Supplementary Motor Area (SMA; including pre-SMA) by receiving continuous visual feedback in the form of a thermometer bar (Figure 1A). To evaluate the effects of training, we examined changes in their brain function during and after training, as well as changes in their cognitive and motor performance using untrained, independently validated biomarkers of HD progression[8,9].
·Figure 1
Results:
Our patients learned to regulate their brain activity during training and showed a progressive increase of the target ROI activation from the first to the last training visit (t(120) = 2.2, p = 0.03; Figure 1B). To evaluate the effects of training on behavior, we compared performance before and after training using a composite score comprising of a-priori selected measures from the Track-HD battery[8,9]. The composite score after training was higher (better) than the baseline measure in 8 out 10 patients, although not significantly so (group mean (SD) = 0.70 (0.68) and 0.76 (0.65) for baseline and post-training respectively; paired t-test t(9) = 2.18, p = 0.057; Figure 2A). Therefore, although all patients successfully learnt to upregulate activity within the target ROI, not all improved in performance. To establish what underlies the improvement, we examined the neural changes during training that correlated with the change in composite score. Contrary to our expectation, improvement in the composite score did not predict increasing activation in the target ROI, but instead in the left putamen (Small-volume-corrected results within the striatum bilaterally; cluster size = 111 voxels, cluster FWE-corrected p < 0.001; Figure 2B). Although the left putamen was not directly targeted during neurofeedback training, its activation during upregulation could have been modulated indirectly via afferent connections to the target ROI. Indeed, improvement in the composite score after training predicted increased functional connectivity from the first to the last training visit between the left putamen and the target ROI (Small-volume-corrected results within the target ROI; cluster size = 41 voxels, cluster FWE-corrected p = 0.010; Figure 2B).
·Figure 2
Conclusions:
We have shown for the first time that HD patients can learn to regulate their own brain activity using neurofeedback training. Crucially, we identified a link between training-related plasticity and improvement in performance. Our results can inform the design of randomized and controlled studies, which could provide stronger evidence on the effectiveness of this approach. Because it is non-invasive, neurofeedback training could be used preventatively or as adjunct treatment to other disease-modifying therapies and restore function in HD and other neurodegenerative diseases.
Disorders of the Nervous System:
Parkinson's Disease and Movement Disorders 2
Imaging Methods:
BOLD fMRI
Multi-Modal Imaging
Learning and Memory:
Neural Plasticity and Recovery of Function 1
Keywords:
Degenerative Disease
Movement Disorder
Plasticity
Other - Neurofeedback training; real-time fMRI; Huntington's disease
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