assessing-corticospinal-excitability-during-goal-directed-reaching

Assessing Corticospinal Excitability During Goal-Directed Reaching Behavior

Reaching is a widely studied behavior in motor physiology and neuroscience research. While reaching has been examined using a variety of behavioral ...

University of Oregon

Motor-evoked potentials (MEPs), elicited by transcranial magnetic stimulation (TMS) over the motor cortex, are reduced during the preparatory period in delayed response tasks. In this study we examined how MEP suppression varies as a function of the anatomical organization of the motor cortex. MEPs were recorded from a left index muscle while participants prepared a hand or leg movement in  or prepared an eye or mouth movement in . In this manner, we assessed if the level of MEP suppression in a hand muscle varied as a function of the anatomical distance between the agonist for the forthcoming movement and the muscle targeted by TMS. MEP suppression was attenuated when the cued effector was anatomically distant from the hand (e.g., leg or facial movement compared with finger movement). A similar effect was observed in  in which MEPs were recorded from a muscle in the leg and the forthcoming movement involved the upper limb or face. These results demonstrate an important constraint on preparatory inhibition: it is sufficiently broad to be manifest in a muscle that is not involved in the task, but it is not global, showing a marked attenuation when the agonist muscle belongs to a different segment of the body.  Using transcranial magnetic stimulation, we examined changes in corticospinal excitability as people prepared to move. Consistent with previous work, we observed a reduction in excitability during the preparatory period, an effect observed in both task-relevant and task-irrelevant muscles. However, this preparatory inhibition is anatomically constrained, attenuated in muscles belonging to a different body segment than the agonist of the forthcoming movement.

Planning face, hand, and leg movements: anatomical constraints on preparatory inhibition.

Accurate and reliable quantification of brain metabolites measured in vivo using H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites.

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide 12 easy-to-implement consensus recommendations and point out the problems that can arise when they are not followed. Furthermore, we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.

A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task.

The combination of electromyography (EMG) and transcranial magnetic stimulation (TMS) offers a powerful non-invasive approach for investigating corticospinal excitability in both humans and animals. Acquiring and analyzing the data produced with this combination of tools requires overcoming multiple technical hurdles. Due in part to these technical hurdles, the field lacks standard routines for EMG data collection and analysis. This poses a problem for study replication and direct comparisons. Although software toolboxes already exist that perform either online EMG data visualization or offline analysis, there currently are no openly available toolboxes that flexibly perform both and also interface directly with peripheral EMG and TMS equipment. Here, we introduce Visualize EMG TMS Analyze (VETA), a MATLAB-based toolbox that supports simultaneous EMG data collection and visualization as well as automated offline processing and is specially tailored for use with motor TMS. The VETA toolbox enables the simultaneous recording of EMG, timed administration of TMS, and presentation of behavioral stimuli from a single computer. These tools also provide a streamlined analysis pipeline with interactive data visualization. Finally, VETA offers a standard EMG data format to facilitate data sharing and open science.

VETA: An Open-Source Matlab-Based Toolbox for the Collection and Analysis of Electromyography Combined With Transcranial Magnetic Stimulation.

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model.  values were derived through parametric bootstrapping of the linear mixed-effects models (denoted ). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of -acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol ( > .90), -acetylaspartate and -acetylaspartylglutamate ( = .13), or glutamate and glutamine ( = .11). Among the smaller resonances, no vendor effects were found for ascorbate ( = .08), aspartate ( > .90), glutathione ( > .90), or lactate ( = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 

Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites.

In our everyday behavior, we frequently cancel one movement while continuing others. Two competing models have been suggested for the cancellation of such specific actions: (1) the abrupt engagement of a unitary global inhibitory mechanism followed by reinitiation of the continuing actions; or (2) a balance between distinct global and selective inhibitory mechanisms. To evaluate these models, we examined behavioral and physiological markers of proactive control, motor preparation, and response inhibition using a combination of behavioral task performance measures, electromyography, electroencephalography, and motor evoked potentials elicited with transcranial magnetic stimulation. Healthy human participants of either sex performed two versions of a stop signal task with cues incorporating proactive control: a unimanual task involving the initiation and inhibition of a single response, and a bimanual task involving the selective stopping of one of two prepared responses. Stopping latencies, motor evoked potentials, and frontal β power (13-20 Hz) did not differ between the unimanual and bimanual tasks. However, evidence for selective proactive control before stopping was manifest in the bimanual condition as changes in corticomotor excitability, μ (9-14 Hz), and β (15-25 Hz) oscillations over sensorimotor cortex. Together, our results favor the recruitment of a single inhibitory stopping mechanism with the net behavioral output depending on the levels of action-specific motor preparation. Response inhibition is a core function of cognitive flexibility and movement control. Previous research has suggested separate mechanisms for selective and global inhibition, yet the evidence is inconclusive. Another line of research has examined the influence of preparation for action stopping, or what is called proactive control, on stopping performance, yet the neural mechanisms underlying this interaction are unknown. We combined transcranial magnetic stimulation, electroencephalography, electromyography, and behavioral measures to compare selective and global inhibition models and to investigate markers of proactive control. The results favor a single inhibitory mechanism over separate selective and global mechanisms but indicate a vital role for preceding motor activity in determining whether and which actions will be stopped.

A Single Mechanism for Global and Selective Response Inhibition under the Influence of Motor Preparation.

Action preparation involves widespread modulation of motor system excitability, but the precise mechanisms are unknown. In this study, we investigated whether intracortical inhibition changes in task-irrelevant muscle representations during action preparation. We used transcranial magnetic stimulation (TMS) combined with electromyography in healthy human adults to measure motor-evoked potentials (MEPs) and cortical silent periods (CSPs) in task-irrelevant muscles during the preparatory period of simple delayed response tasks. In , participants responded with the left index finger in one task condition and the right index finger in another task condition, whereas MEPs and CSPs were measured from the contralateral nonresponding and tonically contracted index finger. During , participants responded with the right pinky finger whereas MEPs and CSPs were measured from the tonically contracted left index finger. In both experiments, MEPs and CSPs were compared between the task preparatory period and a resting intertrial baseline. The CSP duration during response preparation decreased from baseline in every case. A laterality difference was also observed in , with a greater CSP reduction during the preparation of left finger responses compared to right finger responses. Despite reductions in CSP duration, consistent with a release of intracortical inhibition, MEP amplitudes were smaller during action preparation when accounting for background levels of muscle activity, consistent with earlier studies that reported decreased corticospinal excitability. These findings indicate that intracortical inhibition associated with task-irrelevant muscles is transiently released during action preparation and implicate a novel mechanism for the controlled and coordinated release of motor cortex inhibition. In this study, we observed the first evidence of a release of intracortical inhibition in task-irrelevant muscle representations during response preparation. We applied transcranial magnetic stimulation to elicit cortical silent periods in task-irrelevant muscles during response preparation, and observed a consistent decrease in the silent period duration relative to a resting baseline. These findings address the question of whether cortical mechanisms underlie widespread modulation in motor excitability during response preparation.

Response preparation involves a release of intracortical inhibition in task-irrelevant muscles.

Heating of gradient coils and passive shim components is a common cause of instability in the B field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.

Frequency drift in MR spectroscopy at 3T.

Signatures of inhibition within the cortico-spinal pathway are frequently observed during action preparation in humans. Popular theoretical and computational models highlight a critical role for inhibition as the suppressor of motor system output, e.g., to withhold undesired action tendencies or to stop ongoing movements. However, inhibition frequently serves a modulatory role in non-motor systems. For example, in vision and somatosensory systems, inhibition can adjust the relationships between input and output, a computation referred to as gain modulation. Inhibition may modulate gain within the motor system as well. Changes in cortico-spinal inhibition observed during human behavior can reflect adjustments in motor system gain and may be sensitive to latent behavioral states. This review summarizes roles for inhibition in gain modulation, drawing principally on evidence from non-motor systems, and examines the hypothesis that homologous functions operate in the animal and human motor systems to facilitate action preparation.

Article	Year
Planning face, hand, and leg movements: anatomical constraints on preparatory inhibition. Journal of neurophysiology\| PubMed ID: 30785815	2019
Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites. NeuroImage\| PubMed ID: 30840905	2019
A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task. eLife\| PubMed ID: 31033438	2019
VETA: An Open-Source Matlab-Based Toolbox for the Collection and Analysis of Electromyography Combined With Transcranial Magnetic Stimulation. Frontiers in neuroscience\| PubMed ID: 31572120	2019
Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites. Radiology\| PubMed ID: 32043950	2020
A Single Mechanism for Global and Selective Response Inhibition under the Influence of Motor Preparation. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 32928884	2020
Response preparation involves a release of intracortical inhibition in task-irrelevant muscles. Journal of neurophysiology\| PubMed ID: 33356901	2021
Frequency drift in MR spectroscopy at 3T. NeuroImage\| PubMed ID: 34314848	2021
Inhibition for gain modulation in the motor system. Experimental brain research\| PubMed ID: 35347346	2022

Ian Greenhouse

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