Kelm-Nelson Cynthia A, Yang Katie M, Ciucci Michelle R
Department of Surgery, Division of Otolaryngology, University of Wisconsin-Madison, Madison, WI, USA.
Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.
J Parkinsons Dis. 2015;5(4):749-63. doi: 10.3233/JPD-150688.
Parkinson's disease (PD) is a complex neurodegenerative disease with vocal communication deficits that manifest early, progress, and are largely resistant to medical interventions; however, they do respond to exercise-based speech and voice therapies.
To study how exercise-based vocal treatment can affect the progression of communication deficits related to PD, we studied ultrasonic vocalizations (USVs) in rats with homozygous knockout (-/-) of PINK1, a gene mutation known to cause PD, under the manipulation of a behavioral vocal exercise paradigm that allows us to precisely control dose and timing of exercise in the prodromal (prior to diagnosis) stages.
We show that intensive vocal-training rescues frequency range and intensity deficits as well as leads to an increase in call complexity and duration of calls compared to sham-training; however, over time this training regime loses significant effect as the disease progresses. We also show effects of frequent handling and conspecific (male-female) interaction in the sham-training group as they demonstrated significantly higher call rate, intensity, frequency range, and call complexity compared to rats without any form of training and consequently less handling/interaction. Further, we confirm that this model exhibits progressive gross motor deficits that indicate neurodegeneration.
This study suggests that the evolving nature of vocal communication deficits requires an adjustment of therapy targets and more intensive training over the course of this progressive disease and demonstrates the importance of frequent social experiences.
帕金森病（PD）是一种复杂的神经退行性疾病，伴有早期出现、逐渐进展且在很大程度上对医学干预有抵抗性的言语交流缺陷；然而，它们确实对基于运动的言语和嗓音治疗有反应。
为了研究基于运动的嗓音治疗如何影响与PD相关的交流缺陷的进展，我们在一种行为嗓音运动范式的操控下，研究了携带已知会导致PD的基因突变PINK1纯合敲除（-/-）的大鼠的超声发声（USV），这种范式使我们能够在疾病前驱期（诊断前）精确控制运动的剂量和时间。
我们发现，与假训练相比，强化嗓音训练可挽救频率范围和强度缺陷，并导致叫声复杂性增加和叫声持续时间延长；然而，随着疾病进展，这种训练方式会逐渐失去显著效果。我们还显示了假训练组中频繁处理和同种（雌雄）互动的影响，因为与没有任何形式训练且因此处理/互动较少的大鼠相比，它们表现出显著更高的叫声率、强度、频率范围和叫声复杂性。此外，我们证实该模型表现出渐进性的粗大运动缺陷，表明存在神经退行性变。
本研究表明，言语交流缺陷的不断演变的性质需要在这种进行性疾病过程中调整治疗目标并进行更强化的训练，并证明了频繁社交体验的重要性。
