Background

Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise.

Objectives

To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation.

Methods

Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I² tests.

Results

For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32–0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (−0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33–0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09–0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect.

Conclusions

The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of studies as yet with tDCS. More research is needed to establish moderator variables that may affect response to neurostimulation and to optimize treatment parameters in order to achieve stable and durable (and thus clinically relevant) effects.

中文翻译：

---

额叶无创脑刺激对改善精神分裂症阴性症状的中度作用：对照试验的荟萃分析

背景

精神分裂症的阴性症状涉及临床上针对目标的行为的减少，该行为强烈和消极地影响日常功能。现有的治疗方法几乎没有效果，需要新颖的方法。通过重复性经颅磁刺激（rTMS）和经颅直流电刺激（tDCS）进行的非侵入性神经刺激是可能有望实现的新方法。

目标

为了提供有关rTMS和tDCS在额叶皮层上对阴性症状的影响的已发表证据的定量整合，包括对假刺激的影响进行分析。

方法

使用随机效应模型进行荟萃分析，以计算平均加权效应量（Cohen d）。异质性通过使用Cochrans Q和I ²检验进行评估。

结果

对于rTMS治疗，与假刺激相比，加权平均效应大小为0.64（0.32-0.96； k = 22，总N = 827）。与较年轻参与者的研究相比，较年轻参与者的研究显示出更强的效果。对于tDCS研究，发现平均加权效应大小为0.50（-0.07至1.07； k = 5，总N = 134）。对于所有额叶非侵入性神经刺激研究（即TMS和tDCS研究相结合），主动刺激均优于假手术，平均加权效应大小为0.61（24个研究，27个比较，95％置信区间0.33–0.89；总N = 961） 。Sham rTMS（基线-治疗后比较）显示阴性症状显着改善，d = 0.31（0.09–0.52； k = 16，总N = 333）。尽管以前的荟萃分析的功能不足，但我们的荟萃分析的功效只有0.87，可以检测出很小的影响。

结论

现有证据表明，无创前额神经刺激可以改善不良症状。这一发现表明，外侧额叶皮层在自我启动的目标导向行为中起因果作用。rTMS的证据比tDCS的证据更强，尽管这可能是由于tDCS的研究数量很少。需要进行更多的研究来建立可能影响神经刺激反应的调节剂变量，并优化治疗参数，以达到稳定和持久（从而具有临床相关性）的作用。