Neuropsychiatric symptoms are common and disabling in Parkinson’s disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD is challenging, hampered by insufficient insight into underlying mechanisms, lack of objective anxiety measurements, and largely ineffective treatments. In this study, we assessed the intracranial neurophysiological correlates of anxiety in PD patients treated with deep brain stimulation (DBS) in the laboratory and at home. We hypothesized that low-frequency (theta-alpha) activity would be associated with anxiety. We recorded local field potentials (LFP) from the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi) DBS implants in three PD cohorts: 1) patients with recordings (STN) performed in hospital at rest via perioperatively externalized leads, without active stimulation, both ON or OFF dopaminergic medication; 2) patients with recordings (STN or GPi) performed at home while resting, via a chronically implanted commercially available sensing-enabled neurostimulator (Medtronic PerceptTM device), ON dopaminergic medication, with stimulation both on or off; 3) patients with recordings performed at home while engaging in a behavioral task via STN and GPi leads and electrocorticography paddles over premotor cortex connected to an investigational sensing-enabled neurostimulator, ON dopaminergic medication, with stimulation both on or off. Trait anxiety was measured with validated clinical scales in all participants, and state anxiety was measured with momentary assessment scales at multiple time points in the two at-home cohorts. Power in theta (4-8 Hz) and alpha (8-12 Hz) ranges were extracted from the LFP recordings, and their relation with anxiety ratings was assessed using linear mixed-effects models. In total, 33 PD patients (59 hemispheres) were included. Across three independent cohorts, with stimulation off, basal ganglia theta power was positively related to trait anxiety (all p<0.05). Also in a naturalistic setting, with individuals at home at rest with stimulation and medication ON, basal ganglia theta power was positively related to trait anxiety (p<0.05). This relationship held regardless of the hemisphere and DBS target. There was no correlation between trait anxiety and premotor cortical theta-alpha power. There was no within-patient association between basal ganglia theta-alpha power and state anxiety. We showed that basal ganglia theta activity indexes trait anxiety in PD. Our data suggest that theta could be a possible physiomarker of neuropsychiatric symptoms and specifically of anxiety in PD, potentially suitable for guiding advanced DBS treatment tailored to the individual patient’s needs, including non-motor symptoms.

中文翻译：

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帕金森病患者的基底神经节 θ 功率指数 性状焦虑


神经精神症状在帕金森病 （PD） 中很常见且致残，三分之一的患者会出现令人烦恼的焦虑。PD 焦虑的管理具有挑战性，受到对潜在机制的了解不足、缺乏客观的焦虑测量以及基本上无效的治疗所阻碍。在这项研究中，我们评估了在实验室和家中接受深部脑刺激 （DBS） 治疗的 PD 患者焦虑的颅内神经生理学相关性。我们假设低频 （theta-alpha） 活动与焦虑有关。我们在三个 PD 队列中记录了来自丘脑底核 （STN） 或苍白球内部部 （GPi） DBS 植入物的局部场电位 （LFP）：1） 在医院静息时通过围手术期外化导联进行记录 （STN） 的患者，没有主动刺激，开启或关闭多巴胺能药物;2） 在家中休息时通过长期植入的市售传感神经刺激器（美敦力 PerceptTM 设备）进行记录（STN 或 GPi）的患者，服用多巴胺能药物，刺激打开或关闭;3） 在家中进行录音的患者，同时通过 STN 和 GPi 导联和皮层电图桨在连接到研究性传感神经刺激器（ON 多巴胺能药物）的运动前皮层上进行行为任务，刺激打开或关闭。在两个家庭队列中，使用经过验证的临床量表测量所有参与者的特质焦虑，并在多个时间点使用瞬时评估量表测量状态焦虑。 从 LFP 录音中提取 theta （4-8 Hz） 和 alpha （8-12 Hz） 范围内的功率，并使用线性混合效应模型评估它们与焦虑评分的关系。总共纳入 33 例 PD 患者 （59 个半球）。在 3 个独立的队列中，在刺激关闭的情况下，基底神经节 θ 功率与特质焦虑呈正相关 （均 p<0.05）。同样在自然主义环境中，个体在家中休息并接受刺激和药物治疗，基底神经节 θ 功率与特质焦虑呈正相关 （p<0.05）。无论半球和 DBS 靶标如何，这种关系都成立。特质焦虑与运动前皮层 theta-alpha 功率之间没有相关性。基底神经节 θ-α 力量与状态焦虑之间没有患者内部关联。我们发现基底神经节 θ 活性指数 PD 中的性状焦虑。我们的数据表明，θ 可能是神经精神症状的可能物理标志物，特别是 PD 焦虑的生理标志物，可能适合指导根据个体患者的需求（包括非运动症状）量身定制的高级 DBS 治疗。