Breu Maria-Sophie, Schneider Marlieke, Klemt Johannes, Cebi Idil, Gharabaghi Alireza, Weiss Daniel
Centre of Neurology, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany.
Hertie Institute for Clinical Brain Research, Tübingen, Germany.
Front Hum Neurosci. 2022 Jan 26;15:733067. doi: 10.3389/fnhum.2021.733067. eCollection 2021.
Freezing of gait is detrimental to patients with idiopathic Parkinson's disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity.
We analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBS or the substantia nigra pars reticulate (SNr-DBS), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in 'regular gait' and during the 'freezing' episodes.
In stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing.
We found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.
步态冻结对特发性帕金森病(PD)患者有害。其病理生理学表现为皮质、皮质下和脑干回路中运动处理的多级故障,最终导致脊髓模式发生器的运动输出无效。电生理研究指出,步态冻结患者的振荡活动异常,涵盖了包括θ、α和β频段在内的广泛频率范围。我们探讨了与步态冻结相关的肌肉频域活动,并使用深部脑刺激来调节这些节律,从而评估脊髓上对脊髓运动神经元活动的贡献。
我们分析了9名PD步态冻结患者和16名健康对照者(HC)。我们在患者夜间停用多巴胺能药物后,分别在关闭刺激、刺激丘脑底核(STN-DBS)或黑质网状部(SNr-DBS)的情况下对患者进行研究。患者执行通过狭窄障碍物的步行范式。我们分析了胫骨前肌(TA)和腓肠肌(GA)在“正常步态”和“冻结”发作期间的频域谱。
在关闭刺激时,与HC相比,PD步态冻结患者在TA和GA中均表现出α和低β频段的肌肉活动增加。这种活动增加在直行和冻结期间的程度相似。STN-DBS而非SNr-DBS降低了这种活动,并与步态冻结的临床改善情况平行。
我们发现与HC相比,PD步态冻结患者的α和较低β频段的肌肉激活增加,而STN-DBS可使其减弱。未来的研究可能会使用局部场电位、脑电图(EEG)和肌电图(EMG)的联合记录来探究脊髓模式发生器病理激活模式的脊髓上回路机制。