Research project The overall purpose of this research is to bridge the knowledge gaps regarding how deep brain stimulation (DBS) changes pathological brain activity and how this treatment can be optimized for persons who suffer from essential tremor (ET).
By developing new, unique methodology combining motion analysis and neuroimaging, our multidisciplinary research team will be able to establish relationships between lead location, stimulation settings, treatment outcomes and the patient’s specific motor dysfunction on brain and body level.
Essential tremor (ET), the most common movement disorder, causes tremor (high frequent shakings) mainly in hands and arms with a large impact on daily life. DBS effectively reduces tremor by delivering current into specific brain areas through electrodes implanted with stereotactic surgery. Currently, it is poorly understood why some patients develop habituation to stimulation and stimulation-induced movement problems, and we lack precise tools to identify the patients at risk of exhibiting these disabling effects.
To address these knowledge gaps, we will apply and further develop novel multimodal analysis techniques to quantify and explain DBS effects in relation to both body and brain dysfunction.
Project description
Essential tremor (ET), the most common movement disorder, causes tremor in the arms and occasionally in the head, voice, and legs. Also, ataxia (giving unsteady movements with low precision), gait dysfunction and/or balance deficits may occur. The exact mechanisms remain unclear, but involves a tremor-related brain network, causing cerebellar overactivity. ET can be very disabling, and the pharmacological treatment is often insufficient. DBS effectively reduces tremor by delivering current into specific brain areas through electrodes implanted with stereotactic surgery. Currently, it is poorly understood why some patients develop habituation to stimulation and stimulation-induced ataxia, which may lead to an unwanted need to interrupt the DBS. It’s debated whether ET in fact is a group of neurological diseases (subtypes), with different underlying causes and distinct clinical features, which could be one clue to such failures. Furthermore, we lack the tools to identify the patients at risk of exhibiting these disabling effects. Today, the patient is assessed with subjective clinical scales, which do not allow precise quantification of the dysfunction. Also, even if not scientifically demonstrated, a common conception is that stimulation-induced ataxia can be mistaken for a loss of tremor reduction, resulting in erroneous stimulation settings that further deteriorates negative effects.
To address these knowledge gaps, we will apply and further develop novel multimodal analysis techniques to quantify and explain DBS effects in relation to both body and brain dysfunction.
The specific aims are to:
1. Identify ET subtypes by quantifying motor function based on levels of tremor, ataxia, gait dysfunction and balance deficits based on movement features and time series classification from whole-body motion analysis using wearable motion sensors. Further, establish if ET subtype predict treatment outcome by comparing motor function in relation to different DBS settings in ET-patients undergoing DBS treatment (no stimulation, optimal settings and non-optimal settings). This will be done in a cross-sectional experimental design in ET patients in relation to healthy controls.
2. Determine the relationship between motor function and underlying neural activity in healthy persons and ET subtypes in a cross-sectional design. This will be done by new combined time series analysis of multimodal data based on functional Magnetic Resonance Imaging, fMRI, with simultaneous registration of three-dimensional arm and leg movement using special optical cameras. This is a unique technology only available in few labs globally and has not yet been applied in relation to ET.
3. Identify long-term effects from DBS treatment by quantifying motor function and neural correlates in a longitudinal design, following ET from pre-surgery to one-year post-surgery and in comparison to healthy age-matched controls.
