Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, Grenoble Institut Neurosciences, 38000, Grenoble, France.
Adult Psychiatry Department CHU Grenoble Alpes, 38000, Grenoble, France.
Trials. 2023 Feb 24;24(1):141. doi: 10.1186/s13063-023-07160-z.
In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear.
The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.
Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a randomized controlled trial (RCT) with follow-up assessments up to 3 months. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia.
ClinicalTrials.gov NCT05440955. Prospectively registered on July 1, 2022.
除了传统的症状学外，认知缺陷（记忆、注意力、推理、社交功能）也会显著导致精神分裂症患者的残疾和痛苦。认知缺陷与听觉皮层区域中早期听觉过程（EAP）的改变密切相关。初步证据表明，使用一种称为 tDCS（经颅直流电刺激）的可靠且安全的非侵入性脑刺激技术，可以改善精神分裂症的认知缺陷。然而，在 tDCS 治疗后，仍有相当一部分患者没有获得认知益处。此外，tDCS 后认知变化的神经生物学机制在试验中研究甚少，因此仍不清楚。
该研究设计为一项随机、双盲、2 臂平行组、假对照、多中心试验。将 60 名有近期发病和认知障碍的精神分裂症患者随机分为接受真（n=30）或假（n=30）tDCS 组（20 分钟，2 mA，连续 5 天，每天 10 次）。阳极置于左侧背外侧前额叶皮质，阴极置于左侧听觉皮质。在 tDCS 之前（基线）、10 次治疗后以及 1 个月和 3 个月随访时，将评估认知、耐受性、症状、总体结局和 EAP（通过 EEG 和多模态 MRI 测量）。主要结局是在 1 个月随访时，根据 MATRICS 共识认知电池总分，将认知改善≥Z=0.5 的参与者定义为应答者的数量。此外，我们还将测量 EAP 差异如何调节个体从真 tDCS 中获得的认知益处，以及真 tDCS 后应答者的 EAP 测量值是否发生变化。
除了通过针对听觉皮质区域提出新的额颞部 tDCS 方案外，我们还旨在进行一项随机对照试验（RCT），并在 3 个月时进行随访评估。此外，本研究将有助于确定和评估一系列广泛的神经生物学 EAP 测量值，以预测和解释 tDCS 后认知缺陷的改善。该试验的结果将是将 tDCS 作为治疗近期发病精神分裂症认知障碍的治疗工具的一步。
ClinicalTrials.gov NCT05440955. 于 2022 年 7 月 1 日前瞻性注册。
