A Translational, Multimodal Approach to Implementing Non-invasive Paradigms for the Treatment of Oscillopathies
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Pain reduction, measured with a specific scale (NPQ-Neuropathic Pain Questionnaire), as a reduction of at least 4 points
研究概览
简要总结
The need for non-invasive, non-pharmacological and cost-effective therapeutic options has revived the use of transcranial current stimulation, either direct (tDCS) or alternating (tACS), in a wide range of pathologies and cognitive disturbances. Results, although often promising, are not unequivocal, possibly due to different stimulation parameters and sites, or non-homogenous patient selection. tDCS has been widely applied but few studies have focused on tACS which has the advantage of potentially entraining brain oscillations at the same frequency of stimulation. This overcomes the basic mechanism of tDCS which deploys anodal or cathodal currents to broadly excite or inhibit supposedly dysfunctional underlying cortex.
Whether a stimulation paradigm based on sound neurophysiological markers could provide a better and longer-lasting clinical outcome has not yet been ascertained.
The investigators aim to establish, with a trans-disease approach, categories characterized by defective EEG oscillatory activity and related dysfunctional networks. This classification, expected as the result of the first stage of this project, will guide the stimulation paradigm: categories with a pathologically low-band EEG prevalence will be treated with high-frequency tACS, and vice-versa, while the stimulation site will correspond to the defective sites of pathological EEG band maps. Parkinson's disease (PD), the EEG marker of which is a shift towards fast frequencies, and neuropathic pain (NP), with an EEG prevalence of slow bands, will be considered.
In order to categorize pathologies on the basis of their EEG frequencies, EEG power spectrums will be derived from resting EEG, and cortical oscillatory reactivity will be assessed by EEG-TMS (electroencephalographic-Transcranial Magnetic Stimulation) co-registration. This method appears to elicit state-dependent brain oscillatory response and is expected to support power spectrum data. The identified prevailing EEG band will be used subsequently to reconstruct scalp EEG band distribution. tACS paradigms will be tailored according to these findings: the anode will be placed over the scalp area corresponding to the dysfunctional rhythm and frequency will be set in order to correct the prevailing EEG band (slow stimulation if fast frequencies prevail, and vice-versa).
The translational element of this research proposal will consist of its clinical application in day-to-day practice for the benefit of people with the target conditions. The patient-groups, after undergoing the neurophysiology studies, will be tested with disease-specific scales and a neuropsychological battery. A 2-weeks tACS, either real or active sham, protocol will then be performed (30 minutes/day, 5 days/week), associated with an ad hoc rehabilitation protocol (60 minutes/day 5 days/week). During the last day of stimulation, patients will be tested again with the disease specific scales, neuropsychological battery and standard EEG to detect EEG frequencies modifications. At 4-weeks follow up, the same tests and EEG recording will be carried out, to assess the persistence of after-effects.
The expected result is a valid, non-invasive and cost-effective stimulation paradigm based on sound neurophysiologic markers which transcend traditional disease classifications.
详细描述
tDCS has been applied to a spectrum of diseases, including depression, Parkinson's disease (PD), dementia and others, on the basis of the concept of dysfunctional brain areas: modulating the hypo-or hyper-function of the indicated brain regions via anodal or cathodal tDCS has shown evidence of clinical symptom improvement, although generally short lasting and often with discordant results among studies. Conversely, tACS has only rarely been applied to people with disease, with discordant results. Its application to healthy individuals to boost sleep and sleep-related memory formation and working memory has, however, been shown to be effective. If consensus on stimulation patterns (continuous vs. alternating) is, however, lacking, the same holds true for frequencies, although evidence from computational and animal studies demonstrates that tACS is very effective at entraining the network at the frequency of the applied stimulation, with theta noticeably efficacious at improving cognitive performances in memory tasks.
Whether a different paradigm, tailored to specific neurophysiological signatures, and not to the phenotype of the underlying dysfunction (i.e. applying inhibitory tDCS on the hyperfunctioning cortical area of a given disease or vice-versa), could lead to better and long-lasting clinical results is not yet defined.
Therefore, this proposed study has two fundamental questions: 1) is a re-categorization of pathologies based on their oscillatory activities and related scalp distribution. Indeed, the answer the investigators are seeking is whether the investigators could identify clear neurophysiological markers that could lead to a new diagnostic classification. From a translational perspective the question is: 2) could these markers eventually guide therapeutic options? If these points are proved, the investigators expect to expand the results to other oscillopathies (i.e. schizophrenia or insomnia).
The objective of this project is thus two-staged: a first stage will define neurophysiologic markers of diverse diseases, overcoming the traditional symptom-based classification of pathologies. In the second stage, these features will be translated into a tailored non-invasive brain stimulation (NIBS) protocol. Indeed, focusing on oscillatory rhythms dysfunctions, tACS, that entrains specific EEG frequencies, instead of tDCS, that hypo-hyperpolarizes indiscriminately vast brain regions, will be applied.
In the first stage, selected pathologies among the broader spectrum of thalamo-cortical-dysrhythmias (TCDs) will be categorized on the basis of their prevalent EEG rhythm; in addition, oscillatory brain response to external perturbation (frequency bands synchronization or desynchronization in response to TMS stimulation as defined by EEG-TMS co-registration) will be obtained. The identified EEG frequency will subsequently be extracted from EEG to visualize scalp defective areas. The investigators will identify:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PD: diagnosis of idiopathic PD within the last 5 years (UK Brain Bank criteria); stable dose of antiparkinson therapy for at least 4 weeks; total off-medication motor Hoen and Yahr 1-
- •NP: stable chronic pain for at least the preceding six months; score greater than or equal to 3 (0 no pain, 10 worst pain) on the visual analog scale (VAS) for pain perception during the last month before start of stimulation; refractoriness to drugs for pain relief (pain resistance to at least two of these drugs supplied in adequate dosages for 6 months).
排除标准
- •PD: concomitant psychiatric disorder; benzodiazepine treatment; Mini Mental State Examination (MMSE) <26
- •NP: clinically significant or unstable medical or psychiatric disorder, history of substance abuse
结局指标
主要结局
Pain reduction, measured with a specific scale (NPQ-Neuropathic Pain Questionnaire), as a reduction of at least 4 points
时间窗: 1 to 2 years (2nd year)
NPQ (Neuropathic Pain Questionnaire) is a scale measures pain
Proportion of people displaying fast brain oscillatory activity [measured as electroencephalographic (EEG) beta band prevalence]
时间窗: 1 year (first)
EEG power spectral maps will identify this category
Proportion of people dispalying slow brain oscillatory activity [measured as electroencephalographic (EEG) theta band prevalence]
时间窗: 1 year (first)
EEG power spectral maps will identify this category
Improvement ≥ 30% of the total off-medication on a motor performance scale (Unified Parkinson's Disease Rating Scale,part III)
时间窗: 1 to 2 years (2nd year)
UPDRS III is a scale measures motor preformance specifically in Parkinson's Disease
次要结局
- Mean change in Short Form (36) Health Survey for NP(1 to 2 years (2nd year))
- Modifications of frequencies of oscillatory brain activity, measured as spectral power modifications (prevalence of electroencefalographic frequencies) between T0 and T1 and T1 and T2(1 to 2 years (2nd year))
- Mean change in visual analogue scale (VAS) for pain(1 to 2 years (2nd year))
- Neuropsychological testing: improvement between T0 and T1 and T1 and T2.(1 to 2 years (2nd year))