Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease.
Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life.
Department of Bioengineering, University of Utah, Salt Lake City, Utah.|Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
Nathaniel O
NO
King
Department of Bioengineering, University of Utah, Salt Lake City, Utah.
Collin J
CJ
Anderson
Department of Bioengineering, University of Utah, Salt Lake City, Utah.
Alan D
AD
Dorval
D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D004195:Disease Models, Animal; D004401:Dysarthria / Q000209:etiology* / Q000628:therapy*; D005260:Female; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology; D011571:Psychoacoustics; D051381:Rats; D020318:Rats, Long-Evans; D014828:Vocalization, Animal / Q000187:drug effects
D018663:Adrenergic Agents; D016627:Oxidopamine
Parkinson's disease; deep brain stimulation; dysarthria; hypokinesia