Reduced short-interval intracortical inhibition (SICI) is reported in Parkinson's disease (PD) and is considered to reflect abnormal GABAergic inhibitory system of the primary motor cortex in PD. We have recently shown, however, that SICI using anterior-posterior directed currents in the brain was normal in focal dystonia even though that using posterior-anterior currents was abnormal, indicating that the GABAergic system of the primary motor cortex is largely normal in dystonia. Here, we studied SICI in PD to clarify whether the GABAergic system is completely impaired in PD. We used paired-pulse transcranial magnetic stimulation to study SICI at interstimulus intervals of 3 and 4 ms with anterior-posterior or posterior-anterior directed currents in eight PD patients and ten healthy volunteers. The amount of SICI with posterior-anterior directed currents was reduced in PD patients compared with healthy volunteers; in contrast, SICI studied with anterior-posterior directed currents was normal in PD patients. These observations may be due to the difference in I-wave composition generated by the two directed currents and/or the difference in responsible inhibitory interneurons for the inhibition between the two current directions. We suggest that some or a part of inhibitory interneurons are not involved in PD. This discrepancy between SICI using posterior-anterior and anterior-posterior directed currents experiments may provide additional information about the circuits of the motor cortex.
"Kujirai and co-workers concluded that the observed effects are due to the fact that AP-oriented monophasic TMS more readily activates I3 inputs to corticospinal neurons and that these in turn are an important component of associative plasticity in M1
. Adjacent to studies investigating motor cortex plasticity, an influence of current direction on paired pulse protocols
 and on intracortical inhibition (cortical silent period) has been demonstrated
[25-27]. These results confirm the cortical origin of the different properties of PA and AP current direction in the brain. "
[Show abstract][Hide abstract] ABSTRACT: Background
Transcranial magnetic stimulation (TMS) commonly uses so-called monophasic pulses where the initial rapidly changing current flow is followed by a critically dampened return current. It has been shown that a monophasic TMS pulse preferentially excites different cortical circuits in the human motor hand area (M1-HAND), if the induced tissue current has a posterior-to-anterior (PA) or anterior-to-posterior (AP) direction. Here we tested whether similar direction-specific effects could be elicited in M1-HAND using TMS pulses with a half-sine wave configuration.
In 10 young participants, we applied half-sine pulses to the right M1-HAND which elicited PA or AP currents with respect to the orientation of the central sulcus.
Measurements of the motor evoked potential (MEP) revealed that PA half-sine stimulation resulted in lower resting motor threshold (RMT) than AP stimulation. When SI was gradually increased as percentage of maximal stimulator output, the stimulus–response curve (SRC) of MEP amplitude showed a leftward shift for PA as opposed to AP half-sine stimulation. Further, MEP latencies were approximately 1 ms shorter for PA relative to AP half-sine stimulation across the entire stimulus intensity (SI) range tested. When adjusting SI to the respective RMT of PA and AP stimulation, the direction-specific differences in MEP latencies persisted, while the gain function of MEP amplitudes was comparable for PA and AP stimulation.
Using half-sine pulse configuration, single-pulse TMS elicits consistent direction-specific effects in M1-HAND that are similar to TMS with monophasic pulses. The longer MEP latency for AP half-sine stimulation suggests that PA and AP half-sine stimulation preferentially activates different sets of cortical neurons that are involved in the generation of different corticospinal descending volleys.
[Show abstract][Hide abstract] ABSTRACT: Compensatory reorganization of the nigrostriatal system is thought to delay the onset of symptoms in early Parkinson disease (PD). Here we sought evidence that compensation may be a part of a more widespread functional reorganization in sensorimotor networks, including primary motor cortex.
Several neurophysiologic measures known to be abnormal in the motor cortex (M1) of patients with advanced PD were tested on the more and less affected side of 16 newly diagnosed and drug-naive patients with PD and compared with 16 age-matched healthy participants. LTP-like effects were probed using a paired associative stimulation protocol. We also measured short interval intracortical inhibition, intracortical facilitation, cortical silent period, and input/output curves.
The less affected side in patients with PD had preserved intracortical inhibition and a larger response to the plasticity protocol compared to healthy participants. On the more affected side, there was no response to the plasticity protocol and inhibition was reduced. There was no difference in input/output curves between sides or between patients with PD and healthy participants.
Increased motor cortical plasticity on the less affected side is consistent with a functional reorganization of sensorimotor cortex and may represent a compensatory change that contributes to delaying onset of clinical symptoms. Alternatively, it may reflect a maladaptive plasticity that provokes symptom onset. Plasticity deteriorates as the symptoms progress, as seen on the more affected side. The rate of change in paired associative stimulation response over time could be developed into a surrogate marker of disease progression in PD.
[Show abstract][Hide abstract] ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons in the motor cortex, brainstem, and spinal cord. The clinical phenotype of ALS is underscored by a combination of upper and lower motor neuron dysfunction. Although this phenotype was observed over 100 years ago, the site of ALS onset and the pathophysiological mechanisms underlying the development of motor neuron degeneration remain to be elucidated. Transcranial magnetic stimulation (TMS) enables noninvasive assessment of the functional integrity of the motor cortex and its corticomotoneuronal projections. To date, TMS studies have established cortical dysfunction in ALS, with cortical hyperexcitability being an early feature in sporadic forms of ALS and preceding the clinical onset of familial ALS. Taken together, a central origin of ALS is supported by TMS studies, with an anterograde dying-forward mechanism implicated in ALS pathogenesis. Of further relevance, TMS techniques reliably distinguish ALS from mimic disorders, despite a compatible peripheral disease burden, thereby suggesting a potential diagnostic utility of TMS in ALS. This chapter reviews the mechanisms underlying the generation of TMS parameters utilized in assessment of cortical excitability, the contribution of TMS in enhancing the understanding of ALS pathophysiology, and the potential diagnostic utility of TMS techniques in ALS.
Handbook of Clinical Neurology 10/2013; 116C:561-575. DOI:10.1016/B978-0-444-53497-2.00045-0
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