This study investigates the use of patterned repetitive transcranial magnetic stimulation (prTMS) as an intervention for bradykinesia in Parkinson's Disease (PD). More specifically, the study aims to determine whether prTMS over the supplementary motor area (SMA) can reduce severity of bradykinesia in PD patients. This approach may open for more targeted and effective treatment of bradykinesia in PD.
Bradykinesia is one of the core symptoms of Parkinson's Disease (PD) and has multiple facets. Movements become slower and decrease in amplitude. Speed and amplitude of movements decline gradually during repetitive movements, referred to as sequence effect. Spontaneous movements are also reduced, and movement initiation is impaired. These symptoms arise from dysfunction within the brain's motor network, particularly involving the basal ganglia-thalamo-cortical loop. The consequences of bradykinesia are far-reaching, severely affecting the patient's daily life and well-being. Bradykinesia is primarily treated successfully with pharmacologically dopamine precursor levodopa and/or dopamine agonists. However, not all facets of bradykinesia response to dopamine such as the sequence effect and in addition as disease progresses adverse side effects emerge from medication such as dyskinesia which is involuntary choreiform or dystonic movements. These adverse effects require advanced therapies such as invasive treatment with deep brain stimulation (DBS). However, DBS is highly invasive, expensive, and may come with serious side effects. Transcranial magnetic stimulation (TMS) has emerged as a promising non-invasive and cost-effective intervention for alleviating bradykinesia. In particular, patterned repetitive TMS (prTMS) over several brain regions including the supplementary motor area (SMA) has shown potential in modulating dysfunctional neural circuits and improving motor symptoms in patients with PD. Recent evidence suggests that the efficacy of prTMS may be enhanced by aligning stimulation with specific brain states, as the brain is most responsive to plasticity-inducing protocols right before a movement. The current study aims to develop and validate a novel burst-based prTMS protocol called quadri-pulse stimulation (QPS), which consist of high-frequency burst with four pulses in each burst. An excitatory 200 hertz (Hz) QPS protocol has already shown to induce long-lasting plasticity changes and by incorporating the state of the brain the study aim to further enhance the effect of this QPS protocol. Through a cross-over study design the study will apply active QPS right before a movement, active QPS between movement and sham condition before a movement in patients with PD to determine which produces a meaningful reduction in bradykinesia severity measured by Movement Disorder Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) and Modified Bradykinesia Rating Scale (MBRS).
Transcranial magnetic stimulation (TMS) using Axilum Robotics TMS-Cobot using active side of MagVenture Cool-B65 coil
Sham transcranial magnetic stimulation (TMS) using Axilum Robotics TMS-Cobot, flipping the active side of the MagVenture Cool-B65 coil.
DRCMR
Hvidovre, Denmark
RECRUITINGMovement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (3.4-3.8) (MDS-UPDRS-III)
Measure the changes of scores of United Parkinson's Disease Rating Scale Part III in active stimulation compared to sham stimulation. More specifically the bradykinesia scores in 3.4 to 3.8. The total scores range from 0 (good health) to 132 (poor health).
Time frame: Immediately before and after each session of patterned repetitive transcranial magnetic stimulation (prTMS)
Modified Bradykinesia Rating Scale (MBRS)
Measure the changes of scores of MBRS in active stimulation compared to sham stimulation. A score from 0 (normale) to 4 (barely perform the excercise) will be given for speed, amplitude and rhythmed in differnet task relating the bradykinesia,
Time frame: Immediately before and after each session of patterned repetitive transcranial magnetic stimulation (prTMS)
Transcranial evoked potentials (TEPs)
Change in cortical excitability pre-post stimulation over the SMA
Time frame: Immediately before and after each session of patterned repetitive transcranial magnetic stimulation (prTMS)
Change from pre- to post patterned repetitive transcranial stimulation (prTMS) in resting-state EEG spectral power in predefined frequency bands
Spectral power will be quantified in a priori defined frequency bands (e.g., delta, theta, alpha, beta).
Time frame: Immediately before and after each session of patterned repetitive transcranial magnetic stimulation (prTMS)
Hand Grip Test Battery
By using grip force devices we will measure: * Single grip force both cued and non-cued to test rate of force development and yank * Repetitive grip to test sequence effect and fatiguability
Time frame: Immediately before and after each session of patterned repetitive transcranial magnetic stimulation (prTMS)
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
27
Motor Evoked Potentials (MEPs)
Change in cortical excitability pre-post stimulation measured bilateral from the first dorsal interosseous and tibialis anterior
Time frame: Immediately before and after each session of patterned repetitive transcranial magnetic stimulation (prTMS)