Cortical silent period reflects individual differences in action stopping performance

Individual differences in intracortical inhibition during behavioural inhibition

Transcranial magnetic stimulation (TMS) has been applied to a growing number of psychiatric disorders as a neurophysiological probe, a primary brain-mapping tool, and a candidate treatment. Although most investigations have focused on the treatment of major depression, increasing attention has been paid to anxiety disorders. The aim of this study is to summarize published findings about the application of TMS as a putative treatment for anxiety disorders. TMS neurophysiological and mapping findings, both clinical and preclinical, have been included when relevant. We searched Medline, PsycInfo, and the Cochrane Library from 1980 to January 2009 for the terms 'generalized anxiety disorder', 'social anxiety disorder', 'social phobia', 'panic', 'anxiety', or 'posttraumatic stress disorder' in combination with 'TMS', 'cortex excitability', 'rTMS', 'motor threshold', 'motor evoked potential', 'cortical silent period', 'intracortical inhibition', 'neuroimaging', or 'intracortical facilitation'. Most of the therapeutic experiences with repetitive TMS available in the literature are in the form of case reports, not controlled or blinded studies. Stimulation of the right dorsolateral prefrontal cortex, especially at high frequencies, has been reported to reduce anxiety symptoms in posttraumatic stress disorder and panic disorder; nevertheless, results are mixed. A specific role for the right dorsolateral prefrontal cortex in the posttraumatic stress disorder symptom core can be hypothesized. TMS remains an investigational intervention that has not yet gained approval for the clinical treatment of any anxiety disorder. Clinical sham-controlled trials are scarce. Many of these trials have supported the idea that TMS has a significant effect, but in some studies, the effect is small and short lived. The neurobiological correlates suggest possible efficacy for the treatment of social anxiety that still has to be investigated.

Primary objective: To evaluate excitability and inhibition of the motor cortex acutely and longitudinally following mild traumatic brain injury (mTBI).Research design: A longitudinal paired case-control design was used to examine cortical excitability and inhibition in 15 adults who had sustained an mTBI (mean age = 20.8 ± 1.2 years) and 15 matched control participants (mean age = 21.1 ± 1.3 years).Methods and procedures: Participants visited the lab within 72 hours of injury and again at 1, 2, 4 and 8 weeks post-injury. During each visit, transcranial magnetic stimulation was used to examine resting motor threshold (RMT), motor evoked potential peak-to-peak amplitude (MEPamp) and cortical silent period (CSP) duration of the first dorsal interosseous muscle.Main outcomes and results: There were no differences between groups in RMT (p = 0.10) or MEPamp (p = 0.22) at 72 hours post-injury or across the 2-month testing period (p ≥ 0.68), indicating similar cortical excitability. However, the CSP duration was higher in individuals with mTBI, indicating greater intra-cortical inhibition compared with the control group at 72 hours post-injury (p = 0.03) and throughout the 2 months of recovery (p = 0.009).Conclusions: mTBI appeared to have little effect on cortical excitability, but an acute and long-lasting effect on intra-cortical inhibition.

The aim of our study was to measure the effects of the glutamate antagonist riluzole on different parameters of motor excitability, using transcranial magnetic stimulation (TMS) during 7 days of riluzole administration, and to correlate these effects with riluzole plasma levels. Nine healthy volunteers received a dose of 100 mg riluzole from day 1 to 7 of the study period. Electrophysiological examinations were performed on day 1 before and 2 h, 5 h and 8 h after riluzole administration, on day 2, day 3 and day 5 before riluzole administration, and on day 8. Plasma samples were taken simultaneously. The excitability of the motor cortex, supraspinal and spinal motor pathways was tested by studying intracortical facilitation and inhibition, the cortical silent period and motor threshold after TMS, as well as the peripheral silent period and F-wave amplitudes after electrical peripheral nerve stimulation. We found a significant reduction of intracortical facilitation, which correlated significantly with riluzole plasma levels. To a lesser extent, intracortical inhibition was enhanced on day 1, motor threshold was increased on day 8 and F-wave amplitudes were reduced. These changes did not correlate with riluzole plasma levels. We conclude that the main effect of riluzole in vivo is a reduction of intracortical facilitation, which is closely related to the drug's level in the plasma. The most probable mechanism involves an effect on glutamatergic synaptic transmission.

The activity of excitatory and inhibitory neural circuits in the motor cortex can be probed and modified by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), noninvasively. At present, not only has a consensus regarding the interhemispheric effect of high frequency rTMS not been reached, but the attributes of these TMS-related circuits are also poorly understood. To address this question comprehensively, we integrated a single- and paired-pulse TMS evaluation with excitatory 20-Hz rTMS intervention in order to probe the interhemispheric effect on the intracortical circuits by high-frequency rTMS. In the rest state, after 20-Hz rTMS, a significant increase of single-pulse MEP and paired-pulse intracortical facilitation (ICF) in the non-stimulated hemisphere was observed with good test–retest reliability. Intracortical inhibition (measured by the cortical silent period) in the unstimulated hemisphere also increased after rTMS. No significant time–course change was observed in the sham-rTMS group. The results provide the evidence that 20-Hz rTMS induced a reliable interhemispheric facilitatory effect. Findings from the present study suggest that the glutamatergic facilitatory system and the GABAergic inhibitory system may vary synchronously.

Cyclical excitability of the motor cortex in patients with catamenial epilepsy: A transcranial magnetic stimulation study

The pathophysiology of catamenial diseases such as epilepsy is unclear. Therefore, we investigated changes in cortical excitability during anovulatory and ovulatory cycles. Using transcranial magnetic stimulation (TMS), eight healthy women were investigated during anovulatory and 12 during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle, resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. Repeated-measures analysis of variance (anova) and nonparametric methods were used for statistical analysis. A trend was seen for group by phase interaction regarding ICI (F = 2.5, P = 0.10). ICI varied during anovulatory cycles (median: 51.0% on day 8; 45.3% on day -14, 51.0% on day -7, and 28.6% on day 2; P = 0.040), mainly because of an increased inhibition on day 2. ICI was more pronounced in anovulatory cycles on day -14 (P = 0.021), -7 (P = 0.048) and 2 (P = 0.018) compared to ovulatory women who did not show intraindividual changes (P = 0.56). RMT, CSP and ICF showed no significant changes during anovulatory or ovulatory cycles. The results suggest fluctuations in cortical excitability during anovulatory cycles, possibly due to the withdrawal of 'excitatory' oestrogens that initiate menses in anovulatory cycles.

Neurostimulation/neurorecording are tools to study, diagnose, and treat neurological/psychiatric conditions. Both techniques depend on volume conduction between scalp and excitable brain tissue. Here, we examine how neurostimulation with transcranial magnetic stimulation (TMS) is affected by hydration status, a physiological variable that can influence the volume of fluid spaces/cells, excitability, and cellular/global brain functioning. Normal healthy adult participants (32, 9 males) had common motor TMS measures taken in a repeated-measures design from dehydrated (12-h overnight fast/thirst) and rehydrated (identical dehydration protocol followed by rehydration with 1 L water in 1 h) testing days. The target region was left primary motor cortex hand area. Response at the target muscle was recorded with electromyography. Urinalysis confirmed hydration status. Motor hotspot shifted in half of participants. Motor threshold decreased in rehydration, indicating increased excitability. Even after redosing/relocalizing TMS to the new threshold/hotspot, rehydration still showed evidence of increased excitability: recruitment curve measures generally shifted upward and the glutamate-dependent paired-pulse protocol, short intracortical facilitation (SICF), was increased. Short intracortical inhibition (SICI), long intracortical inhibition (LICI), long intracortical facilitation (LICF), and cortical silent period (CSP) were relatively unaffected. The hydration perturbations were mild/subclinical based on the magnitude/speed and urinalysis. Motor TMS measures showed evidence of expected physiological changes of osmotic challenges. Rehydration showed signs of macroscopic and microscopic volume changes including decreased scalp-cortex distance (brain closer to stimulator) and astrocyte swelling-induced glutamate release. Hydration may be a source of variability affecting any techniques dependent on brain volumes/volume conduction. These concepts are important for researchers/clinicians using such techniques or dealing with the wide variety of disease processes involving water balance.NEW & NOTEWORTHY Hydration status can affect brain volumes and excitability, which should affect techniques dependent on electrical volume conduction, including neurostimulation/recording. We test the previously unknown effects of hydration on neurostimulation with TMS and briefly review relevant physiology of hydration. Rehydration showed lower motor threshold, shifted motor hotspot, and generally larger responses even after compensating for threshold/hotspot changes. This is important for clinical and research applications of neurostimulation/neurorecording and the many clinical disorders related to water balance.

Dopamine and dopamine-receptor function are often implicated in behavioral inhibition, and deficiencies within behavioral inhibition processes linked to ADHD, schizophrenia, obsessive-compulsive disorder and drug addiction. In the stop-signal task, which measures the speed of the process of inhibition (stop-signal reaction time, SSRT), psychostimulant-related improvement of SSRT in ADHD is linked with dopamine function. However, the precise nature of dopaminergic control over SSRT remains unclear.This study examined region- and receptor-specific modulation of SSRT in the rat using direct infusions, into the dorsomedial striatum (DMStr) or nucleus accumbens core (NAcbC), of the dopamine D1-receptor (DRD1) antagonist SCH 23390 or dopamine D2-receptor (DRD2) antagonist sulpiride. DRD1 and DRD2 antagonists had contrasting effects on SSRT that were specific to the DMStr. SCH 23390 decreased SSRT with little effect on the go response. Conversely, sulpiride increased SSRT but also increased go-trial reaction time and reduced trial completion at the highest doses. These results suggest that DRD1 and DRD2 function within the DMStr, but not the NAcbC, may act to balance behavioral inhibition in a manner that is independent of behavioral activation.

The aim of the present study was to determine whether significant differences in cortical excitability were evident across different body regions in healthy humans. Threshold tracking transcranial magnetic stimulation (TMS) was undertaken in 28 healthy controls. Short-interval intracortical inhibition [SICI between interstimulus intervals (ISI) 1-7 ms], intracortical facilitation (ICF, between ISI 10-30 ms), resting motor threshold (RMT), cortical silent period (CSP) duration (generated at stimulus intensity 150% RMT), and motor evoked potential amplitude were recorded from the abductor pollicis brevis (APB), tibialis anterior (TA), and trapezius muscles. These muscles were selected as they are frequently affected in neurodegenerative diseases, such as amyotrophic lateral sclerosis. SICI and ICF are measured as a percentage difference between conditioned and an unconditioned test response. SICI was significantly greater when recorded over the APB (9.9 ± 1.5%) and TA (8.6 ± 1.4%) muscles compared with the trapezius (4.5 ± 1.9%, P < 0.05). The CSP duration was significantly shorter (CSPtrapezius, 131.0 ± 6.3 ms; CSPTA, 175.7 ± 9.9 ms; CSPAPB, 188.3 ± 4.0 ms; P < 0.001) and ICF greater ( P < 0.01) in the trapezius muscle. There were no significant correlations between inhibitory and facilitatory processes recorded across the three muscles. The present study established significant differences in cortical excitability across three body regions, with evidence of more prominent inhibition and less facilitation in the limb muscles. NEW & NOTEWORTHY Cortical excitability of muscles with differing motor functions was assessed using threshold tracking transcranial magnetic stimulation. Significantly greater intracortical inhibition and less facilitation were evident over the limb muscles. These findings could relate to differences in the functional organization of the corticomotoneuronal system innervating different muscle regions.

Parallel fast and slow motor inhibition processes in Joint Action coordination

Exploring the links between gut microbiota and excitatory and inhibitory brain processes in alcohol use disorder: A TMS study

To assess cortical excitability changes in patients with chronic neuropathic pain at baseline and after repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. In 22 patients with unilateral hand pain of various neurologic origins and 22 age-matched healthy controls, we studied the following parameters of cortical excitability: motor threshold at rest, motor evoked potential amplitude ratio at two intensities, cortical silent period (CSP), and intracortical inhibition (ICI) and intracortical facilitation. We compared these parameters between healthy subjects and patients at baseline. We also studied excitability changes in the motor cortex corresponding to the painful hand of patients after active or sham rTMS of this cortical region at 1 or 10 Hz. At baseline, CSP was shortened for the both hemispheres of patients vs healthy subjects, in correlation with pain score, while ICI was reduced only for the motor cortex corresponding to the painful hand. Regarding rTMS effects, the single significant change was ICI increase in the motor cortex corresponding to the painful hand, after active 10-Hz rTMS, in correlation with pain relief. Chronic neuropathic pain was associated with motor cortex disinhibition, suggesting impaired GABAergic neurotransmission related to some aspects of pain or to underlying sensory or motor disturbances. The analgesic effects produced by motor cortex stimulation could result, at least partly, from the restoration of defective intracortical inhibitory processes.

Event Abstract Back to Event Brain pathways underlying Response Inhibition and Response Caution Renate Thienel1*, Elise Mansfield1, Patrick S. Cooper1, Andrew Heathcote1, Birte Forstmann2, Pat Michie1, Gavin Cooper1 and Frini Karayanidis1 1 School of Psychology, University of Newcastle, Australia 2 University of Amsterdam, Netherlands Background: Our previous findings suggest that the striatum is instrumental in mediating response caution in a task switching paradigm (Mansfield et al., J. Neurosci 2011, 31:14688-92), and that structural integrity in two separate fronto-striatal networks are associated with adopting an overall more risky or more cautious response threshold. In the present study, we examine whether a similar network underlies response inhibition, as operationalized by a stop signal task. Response inhibition has been shown to be mediated by cortical and subcortical structures within the inferior frontal lobe and the subthalamic nucleus, respectively. We investigate whether structural integrity measures in these regions can explain the relationship between stop signal related event related potential (ERP) components and estimates of stop signal reaction time (SSRT). Finally the relationship between, and the differential structural pathways contributing to, response threshold adjustment (task-switching paradigm) and stop signal response time will be examined. Methods: Diffusion weighted Imaging (DWI), ERP and behavioural data has been collected in 16 healthy participants (24.5 years, 5 male). A correlational analysis was performed for the ERPs and the behavioural measures of both tasks (task switching and stop signal task). Tract based spatial statistics (TBSS) of the DWI data was performed to compare the white matter pathways associated with response thresholds adjustment (task-switching task), and response inhibition (stop-signal task) respectively. These regions were then used to explain variation in ERP data. Results/Discussion: The integrity within distinct structural pathways (DWI data) explained the relationship between (1) ERP measures and response threshold adjustment and (2) ERP measures and SSRTs. Distinct fronto-basal ganglia pathways mediated threshold setting and response suppression. Keywords: task-switching, stop signal task, DWI, fronto-striatal circuits, response inhibition Conference: ACNS-2013 Australasian Cognitive Neuroscience Society Conference, Clayton, Melbourne, Australia, 28 Nov - 1 Dec, 2013. Presentation Type: Poster Topic: Executive Processes Citation: Thienel R, Mansfield E, Cooper PS, Heathcote A, Forstmann B, Michie P, Cooper G and Karayanidis F (2013). Brain pathways underlying Response Inhibition and Response Caution. Conference Abstract: ACNS-2013 Australasian Cognitive Neuroscience Society Conference. doi: 10.3389/conf.fnhum.2013.212.00145 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Sep 2013; Published Online: 25 Nov 2013. * Correspondence: Dr. Renate Thienel, School of Psychology, University of Newcastle, Newcastle, Australia, renate.thienel@newcastle.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis Google Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis Google Scholar Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis PubMed Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Roles of the medial frontal cortices in the selection, storage and retrieval of response tactics in a voluntary arm-reaching task