Increased motor cortical facilitation and decreased inhibition in Parkinson disease

Abstract

Objective: To identify the changes in motor cortical facilitatory and inhibitory circuits in Parkinson disease (PD) by detailed studies of their time courses and interactions.Methods: Short-interval intracortical facilitation (SICF) and short-interval intracortical inhibition (SICI) were measured with a paired-pulse paradigm using transcranial magnetic stimulation. Twelve patients with PD in both ON and OFF medication states and 12 age-matched healthy controls were tested. The first experiment tested the time course of SICF in PD and controls. The second experiment tested SICI at different times corresponding to SICF peaks and troughs to investigate whether SICI was affected by SICF.Results: SICF was increased in PD OFF state and was reduced by dopaminergic medications. The reduction in SICF from the OFF to ON state correlated with the improvement in PD motor signs. SICI was reduced in PD OFF state and was only partially normalized by dopaminergic medications. At SICF peaks, improvement in SICI with medication correlated with improvement in PD motor sign. Principal component analysis showed that variations of SICF and SICI were explained by the same principal component only in the PD OFF group, suggesting that decreased SICI in the OFF state is related to increased SICF. Conclusions:Motor cortical facilitation is increased and inhibition is decreased in PD. Increased cortical facilitation partly accounts for the decreased inhibition, but there is also impairment in synaptic inhibition in PD. Increased cortical facilitation may be a compensatory mechanism in PD. Neurology â 2013;80:1746-1753 GLOSSARY AMT 5 active motor threshold; ANOVA 5 analysis of variance; GABA 5 g-aminobutyric acid; ICF 5 intracortical facilitation; ISI 5 interstimulus interval; I-wave 5 indirect wave; M1 5 primary motor cortex; MEP 5 motor-evoked potential; PD 5 Parkinson disease; RMT 5 rest motor threshold; S1 5 first stimulus; S2 5 second stimulus; SICF 5 short-interval intracortical facilitation; SICI 5 short-interval intracortical inhibition; TMS 5 transcranial magnetic stimulation; UPDRS 5 Unified Parkinson's Disease Rating Scale.The cardinal symptoms of Parkinson disease (PD) arise from dysfunctions of the motor system. 1 Cortical motor commands originate from the primary motor cortex (M1), which is a primary target of basal ganglia output. The balance and interactions between cortical inhibitory and facilitatory circuits determine motor cortical excitability and output. Short-interval intracortical inhibition (SICI) represents a cortical inhibitory process that is measured by paired-pulse transcranial magnetic stimulation (TMS) with a subthreshold first stimulus (S1) suppressing the motor-evoked potential (MEP) generated by a subsequent suprathreshold second stimulus (S2) at interstimulus intervals (ISIs) of 1 to 5 milliseconds.2 Short-interval intracortical facilitation (SICF) represents a cortical facilitatory process whereby a threshold-level S2 facilitates a suprathreshold S1 at 3 distinct peaks of ISIs (1.1-1.5, 2.3-2.9, ...

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

“…Specifically, marked reduction of SICI has been reported Parkinson's disease (PD), suggesting impaired intracortical inhibition. Interestingly, the abnormalities of SICI were partially modulated by dopaminergic therapies [185][186][187]. Others have documented SICI reduction with higher conditioning stimulus intensities, thereby suggesting abnormalities of intracortical facilitatory circuits [188].…”

The Predictability of Motor and Cognitive Impairment According to Brain Asymmetry of Cognitive Evoked Potentials P300 and Features of Symptom Complex in Patients with Parkinson’s Disease

“…В литературе отмечено, что у больных БП может быть усиленный ответ коркового возбуждения при снижении процессов торможения, что рассматривается как вариант компенсации развивающегося дефицита функции ни-гростриальной системы [5,6]. По-видимому, на первых этапах развития БП на стороне моторных нарушений в коре мозга происходит усиленный нейрональный ответ на стимуляцию, что сопровождается повышением ам-плитуды вызванного потенциала.…”

“…Однако при предъявлении невербальных стимулов разница как в амплитуде, так и в ЛП ВП, особенно в лобных отделах мозга, была минимальна [4]. Это обусловлено широким диапазоном различий амплитуд и ЛП ВП в разных точках конвекситальной поверхности головы, например лобных и теменных, а также изменением характера межполушар-ной асимметрии, связанного, по-видимому, с компенса-торной функциональной реорганизацией нейрональной активности в нигростриальной системе, в моторной коре на начальных этапах развития БП [5,6]. Проблему ис-пользования данных когнитивного ВП для прогноза раз-вития когнитивных нарушений при БП осложняют воз-растное снижение амплитуды и увеличение ЛП ВП [3], а также «нулевые» ответы на стимуляцию, что может быть связано с локальной атрофией коры.…”

Effects of Acupuncture Treatment on Lower Limb Spasticity in Patients Following Hemorrhagic Stroke: A Pilot Study

“…It is thought to be an index of GABA receptor-mediated inhibition within the primary motor area and is measured by pairedpulse TMS with a conditioning stimulus (CS) suppressing the MEP caused by a following test stimulus (TS) [17]. SICI is significantly correlated with spasticity, and GABA agonist has been shown to augment SICI (value decreases), whereas GABA inhibitor reduces SICI [18].…”