ABSTRACT

Background

Primary progressive aphasia (PPA) is associated with progressive loss of language functions in the context of irreversible neurodegeneration, for which there is no cure. Speech-language therapy can help preserve language abilities, and most promisingly, interventions like transcranial direct current stimulation (tDCS) have been shown to augment the effectiveness of therapy. However, the underlying mechanism for this enhancement is unknown.

Objectives

We evaluated the behavioural and physiological (using resting-state magnetoencephalography [rsMEG]) effects of contemporary naming treatment provided with tDCS in a patient with an advanced case of nonfluent variant PPA (P01; 67 year old male). P01 was mute but had preserved written abilities, which we aimed to enhance with written naming therapy and excitatory or anodal-tDCS. We hypothesized greater improvement in written performance, particularly immediate gains, maintenance, and generalization, after anodal- than sham-tDCS. Additionally, reductions in oscillatory abnormal activity, as indicated by rsMEG, were expected after repeated sessions of anodal-tDCS with the naming treatment.

Methods

A written picture naming therapy was paired with five sessions of anodal and five sessions of sham high-definition tDCS over two weeks. Anatomical and neurophysiological abnormalities were mapped with structural-MRI and rsMEG, respectively. TDCS was targeted towards an anatomically intact left supramarginal gyrus. The therapy-induced changes in written performance were evaluated on both trained and untrained pictures using Levenshtein Distances (LD). The neurophysiological changes were evaluated by comparing spectral relative power estimates in frequency bands ranging from delta to low-gamma (1–50 Hz), before and after therapy. All evaluations were completed immediately after therapy with sham- and anodal-tDCS, and at a 3-month follow-up.

Results

Compared to sham-tDCS, anodal-tDCS augmented the immediate therapy-induced gains on trained items, as indicated by reductions in LD scores, reflecting improvement in written performance, particularly for more difficult target words. Neural activity at the stimulation spot and in surrounding and remote regions exhibited reduced oscillatory slowing, both immediately after one session (short-term) and after completion of five sessions (long-term) of anodal-tDCS compared to sham-tDCS. This is manifested as decreased theta (1–4 Hz) and increased beta and low-gamma (15–50 Hz) power. No additional gains with anodal-tDCS were found on untrained items (generalization) or at 3-month follow-up (maintenance).

Conclusions

Our findings suggest that five sessions of anodal-tDCS can improve written performance by partially reversing abnormal neural activity and thus boosting the functional capacity of the structurally intact cortex. Longer duration of treatment may be needed for additional gains in maintenance and generalization with anodal-tDCS.

中文翻译：

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对书面命名治疗和高清 tDCS 的行为和神经生理反应：晚期原发性进行性失语症的案例研究

摘要

背景

原发性进行性失语症 (PPA) 与在不可逆的神经退行性变的情况下进行性语言功能丧失有关，对此无法治愈。语言治疗可以帮助保持语言能力，最有希望的是，经颅直流电刺激 (tDCS) 等干预措施已被证明可以增强治疗的有效性。然而，这种增强的潜在机制尚不清楚。

目标

我们评估了 tDCS 提供的当代命名治疗的行为和生理（使用静息态脑磁图 [rsMEG]）对一名晚期非流利变异 PPA 患者（P01；67 岁男性）的影响。P01 是静音的，但保留了书面能力，我们旨在通过书面命名疗法和兴奋性或阳极-tDCS 来增强这种能力。我们假设在 anodal-tDCS 之后，书面表现会有更大的改善，特别是直接收益、维护和泛化。此外，如 rsMEG 所示，在反复使用命名处理的阳极-tDCS 后，预计振荡异常活动会减少。

方法

在两周内，书面图片命名疗法与五次阳极和五次假高清 tDCS 相结合。解剖学和神经生理学异常分别用结构 MRI 和 rsMEG 绘制。TDCS 的目标是解剖上完整的左侧缘上回。使用 Levenshtein 距离 (LD) 在经过训练和未经训练的图片上评估治疗引起的书面表现变化。通过比较治疗前后从 delta 到低伽马（1-50 Hz）的频带中的光谱相对功率估计值来评估神经生理学变化。所有评估均在假和阳极 tDCS 治疗后立即完成，并在 3 个月的随访中完成。

结果

与 sham-tDCS 相比，anodal-tDCS 增加了训练项目的直接治疗诱导收益，如 LD 分数的降低所示，反映了书面表现的改善，特别是对于更难的目标词。与假-tDCS 相比，在阳极-tDCS 的一个会话（短期）之后和五个会话（长期）完成后，刺激点以及周围和偏远区域的神经活动都表现出减少的振荡减慢。这表现为降低的 theta (1-4 Hz) 和增加的 beta 和低伽马 (15-50 Hz) 功率。在未经训练的项目（泛化）或 3 个月的随访（维护）中未发现使用 anodal-tDCS 的额外收益。

结论

我们的研究结果表明，五次阳极-tDCS 可以通过部分逆转异常神经活动来提高书面表现，从而提高结构完整皮层的功能能力。使用 anodal-tDCS 可能需要更长的治疗时间才能获得额外的维持和泛化效果。