Objective:Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.Participants and Methods:We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.Results:At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).Conclusions:Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.

中文翻译：

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6 单侧右半球底丘脑核深部脑刺激治疗帕金森病后语言流畅性提高：植入半球是否是认知能力下降的可改变危险因素？

目的：非运动症状，如轻度认知障碍和痴呆，是帕金森病（PD）致残的主要原因。虽然丘脑底核深部脑刺激 (STN DBS) 对运动症状安全有效，但双侧 DBS 手术后语言流畅性下降的情况已被广泛复制。然而，人们对单侧手术后的认知结果知之甚少。 参与者和方法：我们在一项随机、交叉、双盲研究（SUNDIAL 试验）中招募了 31 名接受单侧 STN-DBS 的 PD 患者。根据症状最严重一侧的治疗选择目标（n = 17 名左半球和 14 名右半球）。所有参与者均在基线、术后 2、4 和 6 个月完成了神经心理学测试（FAS/CFL、AVLT、DKEFS 色词测试）。结果包括语言流畅性、即时和延迟回忆的原始分数，以及 DKEFS 颜色词抑制试验（试验 3）的完成时间。在第 2、4 和 6 个月时，每个参与者的神经刺激类型（定向模式与环形模式）是随机的。我们使用韦尔奇的两样本 t 检验比较了所有认知结果测量的基线分数，并使用线性混合效应模型来检查半球和刺激对认知的纵向影响。由于 COVID-19 研究中期，该测试组被转换为远程神经心理学管理，并且这作为协变量包含在所有统计模型中，以及每个时间点的受教育年限、基线认知评分和左旋多巴等效药物剂量。结果：在基线时，接受左半球植入的患者在语言流畅性方面的得分低于右半球植入的患者 (t(20.66) = -2.49，p = 0.02）。大脑半球之间在立即回忆（p = 0.57）、延迟回忆（p = 0.22）或反应抑制（p = 0.51）方面没有显着差异。术后，左侧 STN DBS 患者在研究期间言语流畅度显着下降 (p = 0.02)，而接受右侧刺激的患者则表现出改善 (p < .001)。刺激参数（方向与环）对言语流畅性、记忆或抑制没有主要影响，但时间、刺激参数和半球对抑制之间存在三向相互作用，使得 STN DBS 患者接受环刺激更快地完成抑制试验（p = 0.035）。手术后，右侧 STN DBS 患者比左侧种植体患者表现出更快的抑制时间 (p = 0.015)。结论：双侧刺激后言语流畅性下降是 DBS 运动障碍最常见的认知后遗症。在这里，我们发现在术后 6 个月内，单侧左侧 STN 植入后，群体语言流畅性水平下降，但右侧 STN DBS 并未出现下降。植入右半球的患者言语流畅度有所提高。与双侧 DBS 手术相比，单侧 DBS 手术，