Transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (DLPFC) has shown some potential as an adjunctive intervention for ameliorating negative symptoms of schizophrenia, but its efficacy requires optimization. Recently, ‘functional targeting’ of stimulation holds promise for advancing tDCS efficacy by coupling tDCS with a cognitive task where the target brain regions are activated by that task and further specifically polarized by tDCS.

The study used 48-channel functional near infra-red spectroscopy (fNIRS) aiming to determine a cognitive task that can effectively induce a cortical activation of the left DLPFC in schizophrenia patients with predominant negative symptoms before running a tDCS trial. Sixty schizophrenia patients with predominant negative symptoms completed measures of clinical and psychosocial functioning characteristics and assessments across cognitive domains. Hemodynamic changes during n-back working memory tasks with different cognitive loads (1-back and 2-back) and verbal fluency test (VFT) were measured using fNIRS. For n-back tasks, greater signal changes were found when the task required elevated cognitive load. One sample t-test revealed that only 2-back task elicited significant activation in left DLPFC (t = 4.23, FDR-corrected p = 0.0007). During VFT, patients failed to show significant task-related activity in left DLPFC (one sample t-test, t = −0.25, FDR-corrected p > 0.05). Our study implies that 2-back task can effectively activate left DLPFC in schizophrenia patients with predominant negative symptoms. This neurophysiologically-validated task is considered highly potential to be executed in conjunction with high-definition tDCS for “functional targeting” of the left DLPFC to treat negative symptoms in a double-blind randomized sham-control trial, registered on ClinicalTrials.gov Registry (ID: NCT05582980).

左背外侧前额叶皮层 (DLPFC) 的经颅直流电刺激 (tDCS) 作为改善精神分裂症阴性症状的辅助干预措施具有一定的潜力，但其疗效需要优化。最近，刺激的“功能靶向”有望通过将 tDCS 与认知任务相结合来提高 tDCS 功效，其中目标大脑区域被该任务激活，并进一步被 tDCS 特异性极化。

该研究使用 48 通道功能性近红外光谱 (fNIRS)，旨在确定一项认知任务，该任务可以在进行 tDCS 试验之前有效诱导具有主要阴性症状的精神分裂症患者左侧 DLPFC 的皮质激活。六十名具有主要阴性症状的精神分裂症患者完成了临床和心理社会功能特征的测量以及跨认知领域的评估。使用 fNIRS 测量具有不同认知负荷（1-back 和 2-back）的 n-back 工作记忆任务和言语流畅性测试 (VFT) 期间的血流动力学变化。对于 n-back 任务，当任务需要更高的认知负荷时，会发现更大的信号变化。一项样本 t 检验显示，只有 2-back 任务会引起左侧 DLPFC 的显着激活（t  = 4.23，FDR 校正p  = 0.0007）。在 VFT 期间，患者未能在左侧 DLPFC 中表现出显着的任务相关活动（一个样本t检验，t  = -0.25，FDR 校正p  > 0.05）。我们的研究表明，2-back 任务可以有效激活阴性症状为主的精神分裂症患者的左侧 DLPFC。这项经过神经生理学验证的任务被认为非常有可能与高清 tDCS 结合执行，以对左侧 DLPFC 进行“功能定位”，以在双盲随机假对照试验中治疗阴性症状，该试验已在 ClinicalTrials.gov 注册中心注册（ ID：NCT05582980）。