Disturbed surround inhibition in preclinical parkinsonism☆
Introduction
Surround inhibition, suppression of excitability in an area surrounding an activated neural network, is a physiological mechanism that focuses neuronal activity and selects an appropriate neuronal response. It is believed to be an essential mechanism in the motor system, where it can aid the selective execution of desired movements (Mink, 1996). Functional existence of surround inhibition is demonstrated in the human motor system, using transcranial magnetic stimulation (TMS) (Sohn and Hallett, 2004b). Motor evoked potential (MEP) amplitude of the little finger muscle was significantly suppressed during voluntary flexion of the index finger, despite an increase in spinal excitability (Sohn and Hallett, 2004b). Modulation of intracortical inhibition could assist the selection of desired movements (with reduced inhibition) as well as the prevention of unwanted movements (with increased inhibition) (Stinear and Byblow, 2003, Zoghi et al., 2003). A disturbance in surround inhibition with impaired modulation of intracortical inhibition was demonstrated in dystonia (Sohn and Hallett, 2004a, Stinear and Byblow, 2004), where co-contraction of surrounding muscles acts as a key mechanism (Vitek, 2002).
The basal ganglia play a major role in the selective performance of desired movements, presumably via the surround inhibition mechanism (Mink, 1996). During voluntary movements, enhanced corticosubthalamopallidal activity inhibits thalamic excitatory output to the motor cortex, providing tonic suppression of the motor cortex. Simultaneously other pallidal neurons projecting to the thalamus act to generate desired movements by decreasing their discharge through focused striatal output via the direct pathway, thereby removing tonic inhibition to the thalamus and releasing the ‘brake’ from the desired cortical generators (Mink, 1996). Therefore, lesions in the basal ganglia circuit often cause disturbances in the control of voluntary movement (Lee and Marsden, 1994). Parkinson disease (PD), which is caused by selective nigrostriatal dysfunction, could provide a good model for investigating the influence of basal ganglia dysfunction on surround inhibition in the motor system. Using an experimental setting similar to previous studies (Sohn and Hallett, 2004a, Sohn and Hallett, 2004b), we evaluated the functional operation of surround inhibition in the asymptomatic hands of hemiparkinsonism patients.
Section snippets
Subjects
Eleven patients with unilateral PD (4 men and 7 women; mean age 57 ± 2.4; range 46–67 yrs) and 8 age-matched right-handed healthy controls (5 men and 3 women; mean age 52 ± 3.8; range 39–67 yrs) participated in this study after giving their written informed consent. This study was approved by the Local Ethics Committee. All patients had never taken antiparkinson medications prior to this study. The diagnosis of PD was made according to the British Brain Bank criteria, and the severity of PD was
Results
The patients’ clinical characteristics are shown in Table 1. The mean symptom duration was 16 ± 3.1 (range 3–36) months. Mean UPDRS motor scale was 11 ± 1.0 (range 6–15). The tested asymptomatic hand was dominant in 8 patients and non-dominant in 3 patients.
All subjects performed index finger flexion selectively and briefly. Accordingly, off-line analysis of EMG recordings demonstrated that ADM was usually quiet or with low-level EMG during voluntary flexion of the index finger in patients
Discussion
As expected, during index finger flexion, MEPs of ADM were significantly enhanced in the patients’ asymptomatic hand, suggesting disturbed surround inhibition. Rigidity could be a main limitation of TMS studies performed on PD patients, since increased muscle tone often produces an enhancement of MEPs. Thus we performed this study on the patients’ asymptomatic hands, where the muscle tone was normal. Comparable background EMG activity of ADM excludes this kind of influence on the present
Acknowledgements
This work was supported by a faculty research grant of Yonsei University College of Medicine for 2003, and the Brain Korea 21 Project for Medical Science, Yonsei University.
References (16)
- et al.
Impairment of motor cortex activation and deactivation in Parkinson’s disease
Clin Neurophysiol
(2001) - et al.
Altered force release control in Parkinson’s disease
Behav Brain Res
(1995) The basal ganglia: focused selection and inhibition of competing motor programs
Prog Neurobiol
(1996)TMS and drugs
Clin Neurophysiol
(2004)- et al.
Strength in Parkinson’s disease: relationship to rate of force generation and clinical status
Ann Neurol
(1996) - et al.
Parkinsonian bradykinesia is due to depression in the rate of rise of muscle activity
Ann Neurol
(1992) - et al.
Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease
Neurology
(2006) - et al.
A physiological mechanism of bradykinesia
Brain
(1980)
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2018, Journal of the Neurological SciencesSafety of transcranial magnetic stimulation in Parkinson's disease: A review of the literature
2013, Parkinsonism and Related DisordersCitation Excerpt :We identified 84 studies utilizing single or paired-pulse techniques in PD patients. This included 71 single-pulse protocols and 24 paired-pulse protocols including 1091 patients with PD [10,17–97] Of these studies, 2 reported adverse events and 1 reported a transient change in motor performance. No seizures were reported, thus the crude risk of seizures is 0 (95% CI: 0.0000–0.0034).
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The authors report no conflict of interest.