Elsevier

Clinical Neurophysiology

Volume 118, Issue 1, January 2007, Pages 155-163
Clinical Neurophysiology

Saccade-related potentials recorded from human subthalamic nucleus

https://doi.org/10.1016/j.clinph.2006.09.016Get rights and content

Abstract

Objective

To investigate an ocular motor role for the STN in Parkinson’s disease (PD) patients.

Methods

Potentials were recorded from deep brain stimulation (DBS) electrodes implanted in the vicinity of STN in five PD patients, while patients simultaneously performed visually cued saccades, self-paced saccades and in two patients self-paced wrist extensions.

Results

Premovement potentials related to visually cued saccades were found in 4/5 patients and 56% (5/9) of potentials showed phase reversal indicating a local generator. Onsets of these potentials began closer to saccade initiation from STN contacts (0.88 ± 0.30 s) than thalamic ones (1.39 ± 0.28 s). Self-paced saccade-related potentials were found in 4/4 patients. Self-paced saccade potential onsets (1.82 ± 0.88 s) were not different from self-paced wrist extension onsets (1.27 ± 0.98 s), suggesting a non-specific mechanism could be responsible for both potentials. 50% (3/6) of potentials to self-paced saccades and 66% (2/3) of potentials to self-paced wrist extensions showed phase reversal. Potentials could be found either ipsilaterally or contralaterally with respect to saccade direction.

Conclusions

These subcortical premovement potentials to saccades are similar to Bereitschaftspotentials and contingent negative variations to limb movements recorded in cortical and subcortical regions.

Significance

These studies further support a role of STN in ocular motor control and suggest a common mechanism of motor preparation for both eye and limb movements in the basal ganglia.

Introduction

Deep brain stimulation (DBS) is a neurosurgical procedure for the implantation of chronic stimulating electrodes in the subthalamic nucleus (STN) of Parkinson’s disease (PD) patients. Before the internalization of the leads and connection to the subdermal battery, it possible to record deep brain potentials from the region of the subthalamic nucleus while the patient performs a motor task (Paradiso et al., 2003, Paradiso et al., 2004).

The average change in electroencephalogram (EEG) potentials relative to an event such as movement initiation or stimulus presentation can be recorded and these event-related potential (ERP) changes are thought to reflect cortical processing. Readiness or Bereitschaftspotentials (BP) can be recorded from scalp electrodes prior to self-paced movement initiation (Kornhuber and Deecke, 1965) in the absence of any cues to move. The contingent negative variation (CNV) is a potential that precedes visually cued movements that begins between a warning/ready cue (S1) and an imperative (S2) cue (Walter et al., 1964). Both potentials can begin 2–3 s prior to movement onset.

Becker and colleagues were the first to investigate self-paced saccade-related potentials (SRPs) and remarked that the presaccadic negativity resembled the BP that preceded self-paced limb movements (Becker et al., 1972). Subsequent studies documented BP and CNV like scalp potentials preceding self-paced and visually cued saccades (Kurtzberg and Vaughan, 1982, Thickbroom and Mastaglia, 1985, Evdokimidis et al., 1997). The premovement potentials to self-paced finger movements are similar in timecourse (and magnitude) to those occurring before saccades, suggesting that the ocular and somatomotor systems may have similar motor preparation mechanisms (Thickbroom and Mastaglia, 1990).

The motor abnormalities observed in PD (bradykinesia/akinesia, tremor and rigidity) stem from a loss of dopaminergic brainstem neurons that disrupts basal ganglia function. This indicates that the basal ganglia normally plays an important motor role in movement initiation or preparation (Denny-Brown and Yanagisawa, 1976, Graybiel, 1990, Hauber, 1998). This is supported by recent studies from our group investigating ERP recordings from thalamus (Paradiso et al., 2004) and subthalamic nucleus (STN) (Paradiso et al., 2003) demonstrating preparatory or premovement potentials that are similar to BPs recorded from scalp electrodes during self-paced motor tasks.

Ocular motor deficits in PD resemble somatomotor symptoms, such as increased reaction time and decreased saccade amplitude (White et al., 1983, Rascol et al., 1989) and the anatomy of BG ocular motor and somatomotor circuits is very similar (Alexander et al., 1986, Parent and Hazrati, 1995), suggesting that the motor role of BG in ocular and somatomotor movements may be similar.

In a recent intraoperative microelectrode study, we reported on single units in the mid-ventral portion of STN responding just before, during and after eye movements (Fawcett et al., 2005). We therefore sought to record SRPs from the DBS contacts that were externalized through the scalp before the internal pulse generator was implanted, and hypothesized that the potentials would be localized to the STN.

Section snippets

Patients

We studied five PD subjects (3 M, 2 F, mean age 57.0 ± 13.1, range 38–72 years, disease duration 11.0 ± 7.1 years, range 6–23), who had implanted STN DBS electrodes (4 bilateral, 1 left-side only). The main features of the patients are shown in Table 1. The patients provided written informed consent and the University Health Network Research Ethics Board approved the study. DBS electrodes were inserted into STN using MRI-guided stereotaxy and intraoperative microelectrode recordings as described

Results

Visually cued and self-paced saccade-related potentials (SRP) were recorded from DBS electrodes in a majority of subjects for each task. Table 2, Table 3 show SRP onset, maximum amplitudes, contact localization and fixation and target light illumination with respect to mean saccade onset. Examples of significant MRP to visually cued (Fig. 2) and self-paced saccades (Fig. 3) from several patients are shown. Values reported here are means ± SD.

Visually cued SRPs were recorded in 4 of 9 contacts

Discussion

In this study, PD patients performed visually cued and self-paced saccades, while simultaneous bilateral recordings were taken via external leads of quadripolar DBS electrodes in the region of STN. DBS recordings showed premovement potentials to visually cued (4 of 5 patients) and self-paced (4 of 4 patients) saccades. These saccade-related potentials (SRPs) were ipsilateral, contralateral or bilateral with respect to saccade direction. In two patients where self-paced wrist movements were also

Acknowledgements

APF is supported by NSERC Canada and the Vision Science Research Program (VSRP) at the University of Toronto. AML is a clinician-scientist supported by CIHR. WDH is supported by Parkinson Society Canada and CIHR. The authors would like to thank Yu-Yan Poon RN for help in recruiting subjects and the subjects themselves for participating in the study.

References (52)

  • N.E. Loveless et al.

    The impact of warning signal intensity on reaction time and components of the contingent negative variation

    Biol Psychol

    (1975)
  • J.W. Mink

    The basal ganglia: focused selection and inhibition of competing motor programs

    Prog Neurobiol

    (1996)
  • Y. Nagai et al.

    Brain activity relating to the contingent negative variation: an fMRI investigation

    Neuroimage

    (2004)
  • A. Parent et al.

    Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry

    Brain Res Brain Res Rev

    (1995)
  • S. Raeva et al.

    Analysis of evoked activity patterns of human thalamic ventrolateral neurons during verbally ordered voluntary movements

    Neuroscience

    (1999)
  • C.S. Rebert

    Cortical and subcortical slow potentials in the monkey’s brain during a preparatory interval

    Electroencephalogr Clin Neurophysiol

    (1972)
  • I. Rektor et al.

    Movement-related potentials in the basal ganglia: a SEEG readiness potential study

    Clin Neurophysiol

    (2001)
  • B. Rouzaire-Dubois et al.

    Bilateral corticosubthalamic nucleus projections: an electrophysiological study in rats with chronic cerebral lesions

    Neuroscience

    (1985)
  • G.W. Thickbroom et al.

    Cerebral events preceding self-paced and visually triggered saccades. A study of presaccadic potentials

    Electroencephalogr Clin Neurophysiol

    (1985)
  • G.W. Thickbroom et al.

    Premotor negativity associated with saccadic eye movement and finger movement: a comparative study

    Brain Res

    (1990)
  • G.E. Alexander et al.

    Parallel organization of functionally segregated circuits linking basal ganglia and cortex

    Annu Rev Neurosci

    (1986)
  • M. Cassidy et al.

    Movement-related changes in synchronization in the human basal ganglia

    Brain

    (2002)
  • A.R. Crossman et al.

    Experimental hemichorea/hemiballismus in the monkey. Studies on the intracerebral site of action in a drug-induced dyskinesia

    Brain

    (1984)
  • L. Deecke et al.

    Distribution of readiness potential, pre-motion positivity, and motor potential of the human cerebral cortex preceding voluntary finger movements

    Exp Brain Res

    (1969)
  • L. Deecke et al.

    Bereitschaftspotential in patients with unilateral lesions of the supplementary motor area

    J Neurol Neurosurg Psychiatry

    (1987)
  • D. Denny-Brown et al.

    The role of the basal ganglia in the initiation of movement

    Res Publ Assoc Res Nerv Ment Dis

    (1976)
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