ReviewTranscranial magnetic stimulation and Parkinson’s disease
Introduction
The pathophysiology of Parkinson’s disease (PD) has long fascinated generations of neurologists, who undertook multiple study approaches [66]. In the past decade, many researchers have focussed their attention on the physiological changes affecting motor cortical areas in PD. While these are the main targets of the integrative activity of basal ganglia, their main output pathway consists of the corticospinal system [80]. On this apparently simple basis, soon after transcranial electrical stimulation (TES) appeared, making studies of corticospinal physiology feasible in intact man [68], the technique was applied to PD patients. The aim was to trace the effects of the disrupted function of basal ganglia on the cortico-motoneuron connection. In fact, the classical TES study of Dick et al. [32] in three patients concluded that the cortico-motoneuron connection was normal in PD, as did the subsequent contribution of Caramia et al. [17] in five parkinsonians. However, these studies merely referred to conduction along corticospinal axons. Indeed, later, TES pulses were shown to largely bypass the cortical gray matter, which precluded information on the ‘upstream’ intracortical modulation of corticifugal activities [28], [31]. The opposite applied to the technique discovered shortly after, i.e. transcranial (electro-) magnetic stimulation (TMS) [5]. Indeed, the use of TMS in PD investigations began about 10 years ago. Then, it had become clear that TMS could provide information not only on the conductivity of corticospinal neurons, but also on other properties of the primary motor cortex, such as excitability [12]. In turn, basic evidence strongly suggested that excitability was under the influence of multiple afferences to the motor cortex itself, among which those arising from the basal ganglia [80]. Hence, a new insight arose into the pathophysiology of PD as well as of other movement disorders. In the present review, we examine separately the findings provided by single-, paired-, and repetitive-pulse TMS investigations. There are many recent reviews and monographs on the basic mechanisms, features and applications of these various forms of TMS, for instance those of Hallett [45] or Mills [69]. Yet, we shall briefly provide the unfamiliar reader with background information covering each TMS variety.
Section snippets
Single pulse-TMS (s-TMS)
s-TMS was originally developed by Barker et al. [5]. Serial capacitors discharge through a wire coil a high peak (∼5000 A) and a very brief (∼100 μs) electrical pulse. This generates a magnetic field that, by changing rapidly, can induce weak electrical currents in conductive structures neighboring (1.5–2 cm) the coil, such as the cerebral cortex. Activation of corticospinal neurons occurs, which finally leads to a muscle twitch in one or more adjacent muscles (the ‘target’ muscles), depending
Paired pulse TMS (p-TMS)
Table 4 details the main p-TMS studies in PD. The methodology of p-TMS dates back to the early 1990s. It is capable of studying a number of physiological phenomena, such as ipsilateral intracortical excitability [58], transcallosal inhibition [38] or cerebellar inhibition [105]. With respect to PD, most studies have dealt with ipsilateral intracortical excitability, at short and sometimes long interstimulus intervals (ISIs). Two stimuli are delivered to the motor cortex through the same coil,
Repetitive TMS (r-TMS)
Table 5 provides details about the main r-TMS studies in PD. Magnetic pulses can be delivered to brain structures in a repetitive fashion through specific devices. The rate of repetition is of fundamental importance as to the physiologic effect. Slow r-TMS is below a frequency of 1 Hz, while rapid-rate r-TMS is above 1 Hz. Other important variables are the number of pulses, the duration of the trains, their repetitions, and the stimulus intensity. Contrary to s- and p-TMS, r-TMS, especially in
Patients
To date, s-TMS analyses have been carried out in about 430 PD patients. d-TMS studies have involved about 70 PD sufferers, while about 125 have been subject to r-TMS procedures, the vast majority of whom for therapeutic purposes. Overall, the mean patient age was 65 years (range 40–75). Homogeneously throughout the studies, patients prevailed of the akineto-rigid type, and their Hohen and Yahr stage [49] was generally II–III. On the contrary, the diagnostic procedures were seldom specified.
Conclusions
Overall, the most consistent results obtained by TMS studies in PD were of the pathophysiological type. Multiple alterations of the motor cortical function, as tested by TMS, emerged. Particularly, excess excitability or reduced inhibition, especially when at ‘rest’, or in response to somesthetic afference. In turn, cortical activation proved defective, or inadequately modulated, when a voluntary output was to be produced. Motor cortical hypoexcitability emerged when studies focussed on
Acknowledgements
We are very grateful to Cristoforo Comi, MD, and Marilena Poletto MD, for their help in collecting references for an early draft of the present paper.
References (123)
- et al.
Abnormal EPSPs evoked by magnetic brain stimulation in hand muscle motoneurons of patients with amyotrophic lateral sclerosis
Electroencephalogr. Clin. Neurophysiol.
(1993) - et al.
Non-invasive magnetic stimulation of human motor cortex (letter)
Lancet
(1985) - et al.
Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson’s disease
Clin. Neurophysiol.
(2001) - et al.
Parkinson’s disease rigidity: EMG in a small hand muscle at ‘rest’
Electroencephalogr. Clin. Neurophysiol.
(1995) - et al.
Neurophysiological evaluation of the central nervous impulse propagation in patients with sensorimotor disturbances
Electroencephalogr. Clin. Neurophysiol.
(1988) - et al.
Impairment of motor cortex activation and deactivation in Parkinson’s disease
Clin. Neurophysiol.
(2001) - et al.
Corticospinal conduction studied with magnetic double stimulation in the intact human
J. Neurol. Sci.
(1992) - et al.
Apomorphine can increase cutaneous inhibition of motor activity in Parkinson’s disease
Electroencephalogr. Clin. Neurophysiol.
(1996) - et al.
Comparison of descending volleys evoked by transcranial magnetic and electric stimulation in conscious humans
Electroencephalogr. Clin. Neurophysiol.
(1998) - et al.
Age-dependent decline in motor evoked potential (MEP) amplitude: with a comment on changes in Parkinson’s disease
Electroencephalogr. Clin. Neurophysiol.
(1991)
The relation between bradykinesia and excitability of the motor cortex assessed using transcranial magnetic stimulation in normal and parkinsonian subjects
Electroencephalogr. Clin. Neurophysiol.
Spinal motor neuron excitability during the silent period after cortical stimulation
Electroencephalogr. Clin. Neurophysiol.
Ipsilateral cortico-cortical inhibition of the motor cortex in various neurological disorders
J. Neurol. Sci.
Silent period revives as a valuable diagnostic tool with transcranial magnetic stimulation
Electroencephalogr. Clin. Neurophysiol.
Abnormalities of central motor conduction in Parkinson’s disease
J. Neurol. Sci.
Improvement in Parkinsonian symptoms after repetitive transcranial magnetic stimulation
J. Neurol. Sci.
Increased cortical inhibition induced by apomorphine in patients with Parkinson’s disease
Neurophysiol. Clin.
The basal ganglia: focused selection and inhibition of competing activity
Prog. Neurobiol.
Shortened silent period produced by magnetic cortical stimulation in patients with Parkinson’s disease
J. Neurol. Sci.
Pathophysiology of the basal ganglia in Parkinson’s disease
Trends Neurosci.
Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression
Lancet
Pre-movement facilitation of motor-evoked potentials in man during transcranial stimulation of the central motor pathways
Brain Res.
Brain excitability and long latency muscular arm responses: non-invasive evaluation in healthy and parkinsonian subjects
Electroencephalogr. Clin. Neurophysiol.
Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee
Electroencephalogr. Clin. Neurophysiol.
Repetitive transcranial magnetic stimulation causes a short-term increase in the duration of the cortical silent period in patients with Parkinson’s disease
Neurosci. Lett.
Short-term motor improvement after sub-threshold 5-Hz repetitive transcranial magnetic stimulation of the primary motor hand area in Parkinson’s disease
J. Neurol. Sci.
Effects of chronic levodopa and pergolide treatment on cortical excitability in Parkinson’s disease: a transcranial magnetic stimulation study
Clin. Neurophysiol.
Assessment of motor neuron excitability in parkinsonian rigidity by the F wave
J. Neurol.
Sensory and motor evoked potentials in multiple system atrophy: a comparative study with Parkinson’s disease
Mov. Disord.
Neurophysiological effects of stimulation through electrodes in the human subthalamic nucleus
Brain
Cortical inhibition in Parkinson’s disease. A study with paired magnetic stimulation
Brain
Effects of repetitive cortical stimulation on the silent period evoked by magnetic stimulation
Exp. Brain Res.
Reaction times and attention in Parkinson’s disease
J. Neurol. Neurosurg. Psychiatry
Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson’s disease or essential tremor and in normal subjects mimicking tremor
Ann. Neurol.
Sensorimotor disinhibition in Parkinson’s disease: effects of levodopa
Ann. Neurol.
Parkinson’s disease rigidity: magnetic motor evoked potentials in a small hand muscle
Neurology
Magnetic brain stimulation: the silent period after the motor evoked potential
Neurology
Pathophysiology of Parkinson’s disease rigidity. Role of corticospinal motor projections
Cortical excitability in cryptogenic localization-related epilepsy: interictal transcranial magnetic stimulation studies
Epilepsia
Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation
Neurology
Time course of corticospinal excitability in reaction time and self-paced movements
Ann. Neurol.
Effects of internal globus pallidus stimulation on motor cortex excitability
Neurology
Effects of magnetic stimulation over supplementary motor area on movement in Parkinson’s disease
Brain
Effects of antipsychotic medication on electromyographic responses to transcranial magnetic stimulation of the motor cortex in schizophrenia
J. Neurol. Neurosurg. Psychiatry
Motor cortex stimulation in intact man. II. Multiple descending volleys
Brain
Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses
J. Physiol. (London)
Conditioning transcranial cortical stimulation (TCCS) by exteroceptive stimulation in parkinsonian patients
Projections from basal ganglia to tegmentum: a subcortical route for explaining the pathophysiology of Parkinson’s disease signs?
J. Neurol.
The corticomotoneurone connection is normal in Parkinson disease
Nature
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