Elsevier

Brain Research

Volume 1260, 13 March 2009, Pages 15-23
Brain Research

Research Report
Subthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient

https://doi.org/10.1016/j.brainres.2008.12.062Get rights and content

Abstract

The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD were compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated — most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity.

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)

  • BeurrierC. et al.

    Subthalamic nucleus neurons switch from single-spike activity to burst-firing mode

    J. Neurosci.

    (1999)
  • BevanM.D. et al.

    Equilibrium potential of GABAA current and implications for rebound burst firing in rat subthalamic neurons in vitro

    J. Neurophysiol.

    (2000)
  • BrownP.

    Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson's disease

    Mov. Disord.

    (2002)
  • CourtemancheR. et al.

    Synchronous, focally modulated β-band oscillations characterize local field potential activity in the striatum of awake behaving monkeys

    J. Neurosci.

    (2003)
  • FilionM. et al.

    Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism

    Brain Res.

    (1991)
  • Cited by (0)

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