Cortical silent period reflects individual differences in action stopping performance

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.

Anatomo-Functional Origins of the Cortical Silent Period: Spotlight on the Basal Ganglia

The so-called cortical silent period (CSP) refers to the temporary interruption of electromyographic signal from a muscle following a motor-evoked potential (MEP) triggered by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). The neurophysiological origins of the CSP are debated. Previous evidence suggests that both spinal and cortical mechanisms may account for the duration of the CSP. However, contextual factors such as cortical fatigue, experimental procedures, attentional load, as well as neuropathology can also influence the CSP duration. The present paper summarizes the most relevant evidence on the mechanisms underlying the duration of the CSP, with a particular focus on the central role of the basal ganglia in the “direct” (excitatory), “indirect” (inhibitory), and “hyperdirect” cortico-subcortical pathways to manage cortical motor inhibition. We propose new methods of interpretation of the CSP related, at least partially, to the inhibitory hyperdirect and indirect pathways in the basal ganglia. This view may help to explain the respective shortening and lengthening of the CSP in various neurological disorders. Shedding light on the complexity of the CSP’s origins, the present review aims at constituting a reference for future work in fundamental research, technological development, and clinical settings.

Cortical silent period

The cortical silent period (cSP) refers to a period of suppression or silencing of ongoing electromyographic (EMG) activity during voluntary muscle contraction induced by a magnetic stimulus over the contralateral primary motor cortex. This chapter summarizes the physiological basis of the cSP, discusses technical aspects and recommendations on how to record and analyze it, and provides an overview of useful clinical applications. Evidence is presented that multiple spinal mechanisms are implicated in the initial part of the cSP, but some may be also active further on, whereas long-lasting cortical inhibitory mechanisms operate throughout the entire cSP, with an emphasis during its later part. The cSP is a highly relevant and clinically useful tool to assess inhibitory corticomotoneuronal mechanisms in health and disease.

Prominent Prolongation of Cortical Silent Period Induced by Transcranial Magnetic Stimulation in Creutzfeldt-Jakob Disease

The cortical silent period (CSP) induced by transcranial magnetic stimulation (TMS) has been reported to be prolonged in 2 Creutzfeldt-Jakob disease (CJD) patients who presented with periodic myoclonus. Herein, we will show a prominent prolongation of TMS-induced CSP in a patient with CJD who did not have periodic myoclonus. The patient was a 66-year-old woman who developed rapidly progressive dementia. No myoclonic jerks were observed. Brain magnetic resonance imaging showed high-intensity lesions in the cerebral cortex, basal ganglia, and thalamus on diffusion-weighted images. Electroencephalography (EEG) showed diffuse and continuous slow waves, but no periodic synchronous discharges (PSDs). A TMS study revealed that the duration of CSP was prominently prolonged: the duration of CSP (370 ms) equaled that of the mean + 6.5 SD of the normal value. One month after admission, the patient exhibited akinetic mutism and developed periodic myoclonus in her limbs. The clinical course was compatible with CJD. To date, CSP has been measured in only 2 CJD patients. The common findings in both cases were marked prolongation of CSP, periodic myoclonus, and PSD on EEG. In short, we demonstrated that TMS-induced CSP was prominently prolonged even at the early stage of CJD without periodic myoclonus or PSD. In other disorders, the CSP has not been reported to be comparably prolonged to that of CJD patients. Therefore, we conclude that TMS-induced CSP could be prominently prolonged even in the early stage of CJD. The marked prolongation of the CSP might be an early biomarker of CJD.

Cortical Silent Period reflects individual differences in action stopping performance

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to behave in a goal directed manner and to regulate impulses and responses. At the behavioral level, the ability to suppress unwanted actions can be measured via the Stop Signal Task, which allows estimating the temporal dynamics underlying successful response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) provides measures of electrophysiological markers of motor inhibition within the primary motor cortex (M1), such as the Cortical Silent period (CSP). Specifically, CSP’s length is a neurophysiological index of the levels of intracortical inhibition within M1, mainly mediated by slow GABAB receptors. Although there is strong evidence that intracortical inhibition varies during both action initiation and action stopping, it is still not clear whether interindividual differences in the neurophysiological markers of intracortical inhibition might contribute to behavioral differences in actual inhibitory control capacities. Hence, we here explored the relationship between individual differences in intracortical inhibition within M1 and behavioral response inhibition. The strength of GABABergic-mediated inhibition in M1 was determined by the length of individuals’ CSP, while the ability to suppress unwanted or inappropriate actions was assessed by the SSRT. We found a significant positive correlation between CSP’s length and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition within M1 seems to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.New & NoteworthyThe present study corroborates the hypothesis that interindividual differences in neurophysiological TMS-derived biomarkers of intracortical inhibition provide a reliable methodology to investigate individual response inhibition capacities. To date, this is the first study to show that interindividual differences in the CSP’s length measured offline provide a viable biomarker of behavioral motor inhibition, and specifically that individuals with longer CSP performed worse at action stopping, compared to individuals with shorter CSP.

1 Hz Repetitive Transcranial Magnetic Stimulation of the Primary Motor Cortex: Impact on Excitability and Task Performance in Healthy Subjects

Objective Neuronavigated repetitive transcranial stimulation (rTMS) at a frequency of 1 Hz was shown to reduce excitability in underlying brain areas while increasing excitability in the opposite hemisphere. In stroke patients, this principle is used to normalize activity between the lesioned and healthy hemispheres and to facilitate rehabilitation. However, standardization is lacking in applied protocols, and there is a poor understanding of the underlying physiologic mechanisms. Furthermore, the influence of hemispheric dominance on the intervention has not been studied before. A systematic evaluation of the effects in healthy subjects would deepen the understanding of these mechanisms and offer insights into ways to improve the intervention. Methods Twenty healthy subjects underwent five 15-minute sessions of neuronavigated rTMS or sham stimulation over their dominant or nondominant motor cortex. Dominance was assessed with the Edinburgh Handedness Inventory. Changes in both hemispheres were measured using behavioral parameters (finger tapping, grip force, and finger dexterity) and TMS measures (resting motor threshold, recruitment curve, motor area, and cortical silent period). Results All subjects tolerated the stimulation well. A pronounced improvement was noted in finger tapping scores over the nonstimulated hemisphere as well as a nonsignificant reduction of the cortical silent period in the stimulated hemisphere, indicating a differential effect of the rTMS on both hemispheres. Grip force remained at the baseline level in the rTMS group while decreasing in the sham group, suggesting the rTMS counterbalanced the effects of fatigue. Lastly, dominance did not influence any of the observed effects. Conclusions This study shows the capability of the applied low-frequency rTMS protocol to modify excitability of underlying brain areas as well as the contralateral hemisphere. It also highlights the need for a better understanding of underlying mechanisms and the identification of predictors for responsiveness to rTMS. However, results should be interpreted with caution because of the small sample size.