Research ReportSubthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient
Introduction
Basal ganglia (BG) structures are involved in multiple, partially segregated parallel loops that modulate cortical activity (Alexander et al., 1986, Alexander and Crutcher, 1990, Alexander, 1994, Hoover and Strick, 1999). Various circuits have been characterized including oculomotor, prefrontal, limbic, and motor loops (Alexander and Crutcher, 1990). These circuits include convergent inputs from the cortex to the striatum before proceeding through different pathways to the output nuclei, the globus pallidus internus (GPi) or substantia nigra pars reticularis (SNpr), which project to the thalamus or other brainstem nuclei. Specific motor loop nuclei include the striatum, globus pallidus externus, Gpi, substantia nigra, subthalamic nucleus (STN), and thalamic motor nuclei.
The primary models of BG physiology include the rate (Albin et al., 1989, DeLong, 1990), selectivity (Mink, 1996), oscillatory (Brown, 2003) and pattern models (Bergman et al., 1994, Soares et al., 2004, Beurrier et al., 1999, Bevan et al., 2000). The rate and selectivity models posit that the BG encode information based on neuronal firing rates, while the oscillatory model suggests information is encoded in specific frequency bands. The pattern model suggests that burst patterns of BG neurons interrupt information transfer in Parkinson disease (PD). Each of these models is supported by a specific derangement in neuronal activity (i.e., discharge rates, oscillatory activities and bursting pattern) in various BG pathologies; however, the nature of these processes during volitional movements in the normal and pathologic conditions is poorly understood.
The primary goal of this study was to contrast neuronal firing rates, oscillatory activity, and bursting patterns of STN neurons during the performance of volitional movements in normal monkeys and Parkinsonian humans. The results demonstrate STN neurons in PD humans have less response variability across multiple dimensions, and suggest that the aggregate effect of PD is a reduction in the information carrying capacity of BG neurons.
Section snippets
Neuronal discharge rates
One-hundred Parkinsonian human and 101 normal monkey STN neurons were isolated. Examination of peri-movement histograms demonstrates considerable differences between PD humans and normal monkeys. Fig. 1 illustrates the peri-movement neuronal rates for neurons classified as either excited, inhibited, or unresponsive for both the PD human (left panel) and the normal monkey (right panel). Peri-movement rates were aligned to the peak velocity in the joystick voltage (grey lines), and the median
Discussion
Abnormal activity patterns of STN neurons play an important role in the pathophysiology of PD. As these patterns change with different phases of movement, it is important that they be assessed using active, reproducible tasks as described above. However, discerning which patterns are pathological is limited by the inability to record STN activity in normal humans. In addition to normal monkeys, STN activity can be evaluated in primates rendered Parkinsonian by the administration of
Patient selection
Human Research conducted in this study was performed in accordance with a protocol approved by the Massachusetts General Hospital Institutional Review Board and was in accordance with appropriate NIH guidelines. The research purpose and potential risks associated with participation in the clinical studies were explained to the human subjects by study personnel other than the operating surgeon, and signed consents for participation were obtained before surgery. Surgical decisions in human
Acknowledgments
The authors would like to acknowledge the efforts of Jane Roberts for her help in preparing the experimental data. Funding was provided by the American Parkinson's Disease Association (JTG), Doris Duke Charitable Foundation (FAJ), and Parkinson Disease Foundation (ENE).
References (31)
- et al.
The functional anatomy of basal ganglia disorders
Trends Neurosci.
(1989) - et al.
Functional architecture of basal ganglia circuits: neural substrates of parallel processing
Trends Neurosci.
(1990) Primate models of movement disorders of basal ganglia origin
Trends Neurosci.
(1990)- et al.
From symphony to cacophony: pathophysiology of the human basal ganglia in Parkinson's disease
Neurosci. Behav. Rev.
(2008) The basal ganglia: focused selection and inhibition of competing motor programs
Prog. Neurobiol.
(1996)- et al.
Basal ganglia oscillations and pathophysiology of movement disorders
Curr. Opin. Neurobiol.
(2006) Basal ganglia-thalamocortical circuits: their role in control of movements
J. Clin. Neurophys.
(1994)- et al.
Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Annual Rev. Neurosci.
(1986) - et al.
Visually guided movements suppress subthalamic oscillations in Parkinson's disease patients
J. Neurosci.
(2004) - et al.
The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism
J. Neurophysiol.
(1994)