Effect of High Intensity Interval Training on Mechanisms of Neuroplasticity and Psychomotor Behaviours in Parkinson's Disease Patients: a Randomized Study With 1-year Follow up
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Electroencephalography (EEG) - EEG power in the beta-band recorded from scalp using surface electrodes.
研究概览
简要总结
There are experimental evidences of the important role of high intensity physical exercise in Parkinson's disease (PD) treatment, that induces similar effects to pharmacotherapy. So far, the mechanisms of the impact of these changes on the brain subcortical and cortical regions functioning, motor activities and cognitive functions are still not clear.
The aim of this longitudinal (prospective) human experiment is to examine the effects of two cycles of 12-weeks high-intensity interval training (HIIT) on: (i) the level of dopamine (DA) in putamen in striatum, (ii) neurophysiological function of subcortical and cortical motor structures and skeletal muscle activity, (iii) psychomotor behaviors critically associated with dopamine dependent neural structures functioning and (iv) neurotrophic factors' secretion level in blood.
The investigators will recruit 40 PD individuals, who will be divided into two groups: one of them will perform two 12-weeks cycles of HIIT (PD-TR), and the other will not be trained (PD-NTR) with HIIT. The investigators will also recruit 20 age-matched healthy controls (H-CO) as additional control group who will not perform the HIIT. The PD-TR group will perform the two 12-weeks cycles of the HIIT, that induces beneficial, neuroplastic changes and alleviates the PD symptoms, what was found in earlier studies. All PD subjects (PD-TR and PD-NTR) will be examined during their medication "OFF-phase" (it means after dopaminergic drugs withdrawal) before (Pre) and after (Post) training cycles (first training cycle - HIIT 1; second training cycle - HIIT 2), and namely: Pre HIIT 1, 1 week-, 1.5 month- and 3 months-Post HIIT 1; and then similarly 1 week-, 1.5 month- and 3 months-Post HIIT 2. The subject from H-CO will be tested only once.
To examine the assumed HIIT-induced changes in brain functioning the investigators will apply: (i) the positron emission tomography (PET), (ii) the functional magnetic resonance imaging (fMRI), (iii) electroencephalography (EEG) and (iv) an analysis of neurotrophic factors secretion level in blood. The investigators will also assess motor and non-motor symptoms of PD and psychomotor behaviors based on neuropsychological tests of cognitive functions and manual dexterity.
The results of this project will help to answer the fundamental questions about HIIT induced mechanisms of neuroplasticity in PD patients, what is important from scientific and treatment-strategy point of view.
详细描述
I. Research Project Objectives
Aim 1. To examine the effect of two HIIT cycles on presynaptic striatal DA availability (in dorsal putamen) in the tested PD patients using PET imaging method with the 18F-dopa - [18F]fluorodopa uptake, which provides in this case a very good index of restored striatal presynaptic dopaminergic function (Brooks and Pavese, 2011).
Hypothesis 1. The presynaptic striatal dopaminergic function will improve (18F-dopa uptake increase) after the first and second bout of HIIT cycle compared to baseline in the PD-TR group, and will sustain in 1 year follow up time frame (3 months after the second HIIT cycle cessation). In the PD-NTR group, the presynaptic striatal dopaminergic function will not improve or even will be worsened (18F-dopa uptake decrease) in the same time interval. Importantly for this hypothesis the annual decrease of putaminal 18F-dopa is about 10% in early PD (Morrish et al., 1995).
Aim 2. To characterize an influence of two HIIT cycles on neurophysiological functions (NPFs) of: (i) motor and cognitive subcortical and cortical structures, (that are critically dependant on the presynaptic DA availability), using fMRI and EEG, and (ii) skeletal muscles engaged in motor task, using surface EMG. The following neurophysiological functions of central nervous system (CNS) will be tested during performance of the DA availability-dependant self initiated index finger motor task and during mental imagery of this motor task (cognitive task): (i) a level of activation of subcortical and cortical structures, and (ii) strength of functional coupling (functional connectivity) between neural structures. For skeletal muscles NPFs', the investigators will study a strategy of motor units activation. Also, since the investigators will record EEG and EMG simultaneously, the investigators will assess strength of cortico-muscular coupling.
Hypothesis 2. NPFs will improve after the first and second bout of HIIT cycle compared to baseline in the PD-TR group, and will sustain in 1 year follow up time frame. Namely, the investigators speculate that for the motor task and mental imagery task in CNS activity, it will be: (1) an increase of activation in substantia nigra (SN), putamen (PUT), primary motor cortex (M1), supplementary motor area (SMA); (2) decrease of activation of lateral premotor cortex (PMC) and cerebellum; with simultaneous (3) increase of functional coupling of: SN with PUT; PUT with M1, PMC, SMA and dorsolateral prefrontal cortex (DLPFC); and DLPFC with M1, PMC, SMA and cerebellum; (4) decrease of functional coupling between M1, PMC, SMA, cerebellum and parietal cortex; and (5) for the mental imagery task the investigators additionally assume an increase of parietal and decrease of occipital cortex activation. For the skeletal muscle function it will be an improvement in recruitment strategy of motor units. Taking into the data from the simultaneous recording of electrical activity of brain cortex and skeletal muscles engaged in motor tasks, the investigators assume strengthening of corticomuscular coupling. In the PD-NTR group NPFs will not improve or even will be worsened in the same time interval and especially after the 1 year from the baseline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for PD patients: age 45-65 years-old; diagnosis of idiopathic PD; and modified Hoehn and Yahr stages between 1.5 and 3
- •for healthy controls: age-matched to PD patients, lack of neurological disorders
- •all participants will also satisfy the following eligibility criteria: (i) proficient in Polish; (ii) no significant cognitive impairments (dementia), as assessed by the MMSE test (Folstein et al., 1975) score ≥ 27; (iii) no prior history of neurological, psychiatric, or other disorders that may influence CNS structure and function; (iv) no current medication to affect cognitive psychomotor functioning (opioid analgesics, anxiolytics or antidepressants) and (v) signed informed consent.
排除标准
- •for PD patients: (1) presence of other neurological disorders, (2) any cardiovascular and respiratory system restrictions and/or motor deficits that could limit performance in high-speed pedaling on a cycle ergometer or in the conventional physical therapy and (3) practicing any regular intensive physical activity except for physical therapy for PD
- •for healthy controls: presence of neurological disorders
- •for all tested subjects, an additional exclusion criterion for the PET and fMRI experiments will be a claustrophobia.
结局指标
主要结局
Electroencephalography (EEG) - EEG power in the beta-band recorded from scalp using surface electrodes.
时间窗: 3-months Post-HIIT 2
To evaluate neurophysiological functions of brain cortical structures, electroencephalography (EEG - electrical activity of brain cortex) will be recorded from scalp using 128-chanel system. The recordings will be conducted at rest and during self initiated index finger motor task and during mental imagery of this motor task. The recordings will be analyzed as the EEG power in the beta-band (≈13-35 Hz) and expressed in decibels \[dB\].
Electromyography (EMG) - recordings of electrical activity of skeletal muscles using surface electrodes.
时间窗: 3-months Post-HIIT 2
To evaluate neurophysiological functions of muscles engaged in an activity (hand muscles), electromyography (EMG - recordings of electrical activity of skeletal muscles) will be collected using surface electrodes, during index finger motor tasks and at rest. The recordings will be expressed in millivolts \[mV\].
Positron Emission Tomography (PET) with 18F-dopa - PET imaging with [18F]fluorodopa uptake.
时间窗: 3-months Post-HIIT 2
To examine presynaptic striatal DA availability (in dorsal putamen) using PET imaging method with the 18F-dopa - \[18F\]fluorodopa uptake. The recordings will be expressed in Ki ref values \[Ki ref\] and Standard Uptake Values \[SUV\].
functional Magnetic Resonance Imaging (fMRI) - metabolic activity of brain recorded with MRI scanner.
时间窗: 3-months Post-HIIT 2
To evaluate neurophysiological functions of brain subcortical and cortical structures using MRI scanner. The recordings will be conducted at rest and during self initiated index finger motor task and during mental imagery of this motor task. The image recordings will express metabolic brain activity as expressed in fMRI response \[% BOLD signal\].
Electroencephalography (EEG) - amplitude of EEG event related potentials of brain cortex recorded from scalp using surface electrodes.
时间窗: 3-months Post-HIIT 2
To evaluate neurophysiological functions of brain cortical structures, electroencephalography (EEG - electrical activity of brain cortex) will be recorded from scalp using 128-chanel system. The recordings will be conducted at rest and during self initiated index finger motor task and during mental imagery of this motor task. The recordings will be analyzed as an amplitude of event related potentials and expressed in microvolts \[µV\].
Electroencephalography (EEG) - latency of EEG event related potentials of brain cortex recorded from scalp using surface electrodes.
时间窗: 3-months Post-HIIT 2
To evaluate neurophysiological functions of brain cortical structures, electroencephalography (EEG - electrical activity of brain cortex) will be recorded from scalp using 128-chanel system. The recordings will be conducted at rest and during self initiated index finger motor task and during mental imagery of this motor task. The recordings will be analyzed as a latency of event related potentials and expressed in milliseconds \[ms\].
Purdue Pegboard Test (PPT) - neuropsychological test
时间窗: 3-months Post-HIIT 2
To evaluate executive function and bimanual dexterity. The Purdue Pegboard consists of a test board, score sheets and elements to work with: pins, collars, washers. Subjects are instructed to insert pins to holes in the board or build the sets with the elements in a fixed time. The final score is the number of pins inserted or built sets \[number of pins or sets\].
ST-II - Stroop Test, part II
时间窗: 3-months Post-HIIT 2
ST-II is used as a psychological measure of selective attention and inhibition, measured as performance time (the shorter the time the better performance), expressed in \[s\].
UPDRS - unified Parkinson's disease rating scale
时间窗: 3-months Post-HIIT 2
Motor and non-motor Parkinson's disease signs/symptoms will be evaluated using UPDRS (sections I - III, that include the items 1 -31). Each item is expressed in \[points\] from 0 to 4 points, with an interpretation that the higher value means the severe accentuation of sign/symptom. The total score will be reported, as the sum of the points of the sections I-III (the score in the range 0 - 176 points) and each section's score will be reported as well, i.e.: the sum of the points of the section I (sum of points for items 1-4 in the range 0 - 16 points), the sum of the points of the section II (sum of points for items 5-17 in the range 0 - 52 points), the sum of the points of the section III (sum of points for items 18-31 in the range 0 - 108 points).
BDNF - brain derived neurotrophic factor
时间窗: 3-months Post-HIIT 2
BDNF secretion level in blood expressed in \[pg/mL\]
TMT-B - trail making test, part B
时间窗: 3-months Post-HIIT 2
TMT-B is a psychological measure of executive function, measured as performance time (the shorter the time the better performance), expressed in \[s\].
IGF 1 - insulin-like growth factor 1
时间窗: 3-months Post-HIIT 2
IGF 1 secretion level in blood expressed in \[pg/mL\]
TMT-A - trail making test, part A
时间窗: 3-months Post-HIIT 2
TMT-A is a psychological measure of cognitive processing speed, measured as performance time (the shorter the time the better performance), expressed in \[s\].
ST-I - Stroop Test, part I
时间窗: 3-months Post-HIIT 2
ST-I is used as a psychological measure of processing speed, measured as performance time (the shorter the time the better performance), expressed in \[s\].
NGF - nerve growth factor
时间窗: 3-months Post-HIIT 2
NGF secretion level in blood expressed in \[pg/mL\]
Val66Met polymorphism of BDNF - genotyping of BDNF polymorphism
时间窗: Pre-HIIT 1 - it means up to 1-week before the HIIT 1 starts
The single nucleotide polymorphism (SNP) BDNF Val66Met variant (rs 6265) will be genotyped by using the TaqMan SNP genotyping assay. Thermal cycling and end-point PCR (polymerase chain reaction) analysis will be performed on the Rotor-Gene Q 5plex real-time PCR Cycler and will be analyzed by Q-Rex-software. Genotype of BDNF polymorphism will be expressed in percentge values \[% of genotype\].
次要结局
- H&Y scale - Hoehn and Yahr scale(3-months Post-HIIT 2)
- S&E DLA scale - Schwab and England Daily Living Activity Scale(3-months Post-HIIT 2)
- MMSE - Mini Mental State Examination(Pre-HIIT 1 - it means up to 1-week before the HIIT 1 starts)
研究者
Jaroslaw Marusiak
Principal Investigator
Wroclaw University of Health and Sport Sciences