Balance, gait, speech, and swallowing deficits are major causes of disability in patients with Parkinson's disease (PD). In many patients, these """"""""axial symptoms"""""""" are resistant to levodopa therapy. A potential advantage of deep brain stimulation (DBS) of globus pallidus internal (GPi) and the subthalamic nucleus (STN) could be improvement of these axial motor symptoms. Our long-term goal is to determine the effects off DBS on axial motor control in order to understand the role of the basal ganglia in centrally (voluntarily) and peripherally (automatically) initiated axial movements. We hypothesize that there are multiple motor outputs from the basal ganglia with differing sensitivity to dopamine and DBS. The goal of this project is to distinguish functionally different basal ganglia control mechanisms for the axial motor system by their unique patterns of response to DBS and levodopa when used separately and when used in combination. We hypothesize that DBS will he more effective than levodopa and that STN stimulation will be more effective than GPi stimulation for axial parkinsonian symptoms. This project will take advantage of a unique opportunity to rigorously quantify the effects of chronic DBS in radiologically-identified human basal ganglia in a randomized, double-blind study. These studies will quantify forces and movements in two types of postural and oromotor tasks: peripherally triggered, automatic responses to external cues and centrally-initiated voluntary movements.
The specific aims are: (1) To determine how DBS affects centrally-initiated and peripherally-triggered postural control. (2) To determine how DBS affects centrally-initiated and peripherally-triggered oromotor control. (3) To investigate the interactions of DBS and levodopa treatment on postural and oromotor control. (4) To determine effects of the site (GPi versus STN) of DBS on postural and oromotor control. These experiments will quantify the efficacy of DBS and levodopa both separately and when combined for balance and oromotor deficits in patients with PD. Quantifying two types of postural and oromotor control in the same subjects will also substantially increase our understanding of the role of the basal ganglia in axial motor control.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG019706-03
Application #
6626445
Study Section
Special Emphasis Panel (ZNS1-SRB-K (01))
Program Officer
Finkelstein, Judith A
Project Start
2001-03-01
Project End
2005-12-31
Budget Start
2003-01-15
Budget End
2003-12-31
Support Year
3
Fiscal Year
2003
Total Cost
$226,500
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
St George, R J; Carlson-Kuhta, P; King, L A et al. (2015) Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi. J Neurophysiol 114:1417-23
St George, Rebecca J; Carlson-Kuhta, Patricia; Nutt, John G et al. (2014) The effect of deep brain stimulation randomized by site on balance in Parkinson's disease. Mov Disord 29:949-53
St George, Rebecca J; Carlson-Kuhta, Patricia; Burchiel, Kim J et al. (2012) The effects of subthalamic and pallidal deep brain stimulation on postural responses in patients with Parkinson disease. J Neurosurg 116:1347-56
Rocchi, Laura; Carlson-Kuhta, Patricia; Chiari, Lorenzo et al. (2012) Effects of deep brain stimulation in the subthalamic nucleus or globus pallidus internus on step initiation in Parkinson disease: laboratory investigation. J Neurosurg 117:1141-9
Robertson, Lee T; St George, Rebecca J; Carlson-Kuhta, Patricia et al. (2011) Site of deep brain stimulation and jaw velocity in Parkinson disease. J Neurosurg 115:985-94
Zampieri, Cris; Salarian, Arash; Carlson-Kuhta, Patricia et al. (2011) Assessing mobility at home in people with early Parkinson's disease using an instrumented Timed Up and Go test. Parkinsonism Relat Disord 17:277-80
King, Laurie A; St George, Rebecca J; Carlson-Kuhta, Patricia et al. (2010) Preparation for compensatory forward stepping in Parkinson's disease. Arch Phys Med Rehabil 91:1332-8
Horak, Fay B (2006) Postural orientation and equilibrium: what do we need to know about neural control of balance to prevent falls? Age Ageing 35 Suppl 2:ii7-ii11
Rocchi, Laura; Chiari, Lorenzo; Mancini, Martina et al. (2006) Step initiation in Parkinson's disease: influence of initial stance conditions. Neurosci Lett 406:128-32
Robertson, Lee T; Levy, Jay H; Petrisor, Daniel et al. (2003) Vibration perception thresholds of human maxillary and mandibular central incisors. Arch Oral Biol 48:309-16