Reproducibility of neuroplastic responses induced by continuous theta-burst stimulation

See Attache

Modulation of dorsal premotor cortex differentially influences I‐wave excitability in primary motor cortex of young and older adults

First published: 16 May 2023Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I-wave excitability inM1of young and older adults. Twenty-two young (mean±SD, 22.9±2.9 years) and 20 older (66.6 ± 4.2 years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior–anterior (PA) and anterior–posterior (AP) current single-pulse TMS to assess corticospinal excitability (PA1mV; AP1mV; PA0.5mV, early; AP0.5mV, late), and paired-pulse TMS short intracortical facilitation for I-wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA1mV and AP1mV MEPs in both age groups (both P < 0.05), the time course of this effect was delayed for AP1mV in older adults (P = 0.001). Furthermore, while AP0.5mV, PA SICF and AP SICF were potentiated in both groups (all P < 0.05), potentiation of PA0.5mV was only apparent in young adults (P < 0.0001).While PMd influences early and late I-wave excitability in young adults, direct PMdmodulation of the early circuits is specifically reduced in older adults.Wei-Yeh Liao, George M. Opie, Ulf Ziemann, and John G. Semmle

Effects of prolonged and acute muscle pain on the force control strategy during isometric contractions

Musculoskeletal pain is associated with multiple adaptions in movement control. This study aimed to determine whether changes in movement control acquired during acute pain are maintained over days of pain exposure. On day 0, the extensor carpi radialis brevis muscle of healthy participants was injected with nerve growth factor (NGF) to induce persistent movement-evoked pain (n\ua0=\ua013) or isotonic saline as a control (n\ua0=\ua013). On day 2, short-lasting pain was induced by injection of hypertonic saline into extensor carpi radialis brevis muscles of all participants. Three-dimensional force components were recorded during submaximal isometric wrist extensions on day 0, day 4, and before, during, and after saline-induced pain on day 2. Standard deviation (variation of task-related force) and total excursion of center of pressure (variation of force direction) were assessed. Maximal movement-evoked pain was 3.3\ua0±\ua0.4 (0–10 numeric scale) in the NGF-group on day 2 whereas maximum saline-induced pain was 6.8\ua0±\ua0.3\ua0cm (10-cm visual analog scale). The difference in centroid position of force direction relative to day 0 was greater in the NGF group than in the control group (P\ua

Regionally aggregated, stitched and de‐drifted CMIP‐climate data, processed with netCDF‐SCM v2.0.0

The world's most complex climate models are currently running a range of experiments as part of the Sixth Coupled Model Intercomparison Project (CMIP6). Added to the output from the Fifth Coupled Model Intercomparison Project (CMIP5), the total data volume will be in the order of 20PB. Here, we present a dataset of annual, monthly, global, hemispheric and land/ocean means derived from a selection of experiments of key interest to climate data analysts and reduced complexity climate modellers. The derived dataset is a key part of validating, calibrating and developing reduced complexity climate models against the behaviour of more physically complete models. In addition to its use for reduced complexity climate modellers, we aim to make our data accessible to other research communities. We facilitate this in a number of ways. Firstly, given the focus on annual, monthly, global, hemispheric and land/ocean mean quantities, our dataset is orders of magnitude smaller than the source data and hence does not require specialized ‘big data’ expertise. Secondly, again because of its smaller size, we are able to offer our dataset in a text-based format, greatly reducing the computational expertise required to work with CMIP output. Thirdly, we enable data provenance and integrity control by tracking all source metadata and providing tools which check whether a dataset has been retracted, that is identified as erroneous. The resulting dataset is updated as new CMIP6 results become available and we provide a stable access point to allow automated downloads. Along with our accompanying website (cmip6.science.unimelb.edu.au), we believe this dataset provides a unique community resource, as well as allowing non-specialists to access CMIP data in a new, user-friendly way

Boosting brain plasticity in older adults with non-invasive brain co-stimulation

Abstract not availableJohn G.Semmler, George M.Opi

Preferential activation of unique motor cortical networks with transcranial magnetic stimulation: a review of the physiological, functional, and clinical evidence

Objectives: The corticospinal volley produced by application of transcranial magnetic stimulation (TMS) over primary motor cortex consists of a number of waves generated by trans-synaptic input from interneuronal circuits. These indirect (I)-waves mediate the sensitivity of TMS to cortical plasticity and intracortical excitability and can be assessed by altering the direction of cortical current induced by TMS. While this methodological approach has been conventionally viewed as preferentially recruiting early or late I-wave inputs from a given populations of neurons, growing evidence suggests recruitment of different neuronal populations, and this would strongly influence interpretation and application of these measures. The aim of this review is therefore to consider the physiological, functional, and clinical evidence for the independence of the neuronal circuits activated by different current directions. Materials and Methods: To provide the relevant context, we begin with an overview of TMS methodology, focusing on the different techniques used to quantify I-waves. We then comprehensively review the literature that has used variations in coil orientation to investigate the I-wave circuits, grouping studies based on the neurophysiological, functional, and clinical relevance of their outcomes. Results: Review of the existing literature reveals significant evidence supporting the idea that varying current direction can recruit different neuronal populations having unique functionally and clinically relevant characteristics. Conclusions: Further research providing greater characterization of the I-wave circuits activated with different current directions is required. This will facilitate the development of interventions that are able to modulate specific intracortical circuits, which will be an important application of TMS.George M. Opie, John G. Semmle

Threshold Tracked Short-Interval Intracortical Inhibition More Closely Predicts the Cortical Response to Transcranial Magnetic Stimulation

Vol. 25(4) pp 614-623Objectives: Short-interval intracortical inhibition (SICI) is a paired-pulse transcranial magnetic stimulation (TMS) technique that is commonly used to quantify intracortical inhibitory tone in the primary motor cortex. Whereas conventional measures of SICI (CSICI) quantify inhibition by the amplitude of the motor evoked potential (MEP), alternative measures involving threshold tracked SICI (TT-SICI) instead record the TMS intensity required to maintain a consistent MEP amplitude. Although both C-SICI and TT-SICI are thought to reflect inhibition mediated by γ-aminobutyric acid type A (GABAA) receptors, recent evidence suggests that the mechanisms involved with each measure may not be equivalent. This study aimed to use combined TMSelectroencephalography (TMS-EEG) to investigate the cortical mechanisms contributing to C-SICI and TT-SICI. Materials and Methods: In 20 young adults (30.6 ± 8.1 years), C-SICI and TT-SICI were recorded with multiple conditioning intensities, using both posterior-to-anterior (PA) and anterior-to-posterior (AP) induced currents, and this was compared with the TMS-evoked EEG potential (TEP). Results: We found no relationship between the magnitude of C-SICI and TT-SICI within each current direction. However, there was a positive relationship between the slope (derived from multiple conditioning intensities) of inhibition recorded with C-SICI and TT-SICI, but only with a PA current. Furthermore, irrespective of conditioning intensity or current direction, measures of C-SICI were unrelated to TEP amplitude. In contrast, TT-SICI was predicted by the P30 generated with AP stimulation. Conclusions: Our findings further demonstrate that C-SICI and TT-SICI likely reflect different facets of GABAA-mediated processes, with inhibition produced by TT-SICI appearing to align more closely with TMS-EEG measures of cortical excitability.Ryoki Sasaki, John G. Semmler, George M. Opi

Inter- and intra-subject variability of motor cortex plasticity following continuous theta-burst stimulation

Background: The potential of non-invasive brain stimulation (NIBS) for studying, and inducing, functionally relevant neuroplasticity is dependent on protocols that can induce lasting, robust and reliable effects. A current limiting factor is the large inter- and intra-subject variability in NIBS-induced neuroplastic responses. There has been some study of inter-subject response variability and factors that contribute to it; however, intra-subject response variability has, so far, received little investigation. Objectives: By testing participants on multiple occasions we aimed to (1) compare inter- and intra-subject variability of neuroplastic responses induced by continuous theta-burst stimulation (cTBS); (2) determine whether the transcranial magnetic stimulation (TMS) intensity used to measure cTBS-induced neuroplastic responses contributes to response variability; (3) determine whether assessment of factors known to influence response variability can be used to explain some of the variability in cTBS-induced neuroplastic responses across experimental sessions. Methods: In three separate experimental sessions, motor-evoked potential (MEP) input–output (IO) curves were obtained before and after cTBS, and questionnaire-based assessments of physical activity and perceived stress were obtained. Results: cTBS-induced MEP suppression was greatest at the upper end of the IO curve (150–180% resting motor threshold; RMT) and most consistent across subjects and across experimental sessions when assessed with a TMS intensity of 150% RMT. The magnitude of cTBS-induced MEP suppression evoked at 150% RMT correlated with self-reported perceived stress, but not with self-reported physical activity. Conclusions: The most reliable TMS intensity to probe cTBS-induced long-term depression (LTD)-like neuroplastic responses is 150% RMT. This is unlikely to simply be a ceiling effect and, we suggest, may be due to changes in the descending volley evoked at higher stimulus intensities. The perceived stress scale appears to be sufficiently sensitive to measure the influence of subject stress on LTD-like neuroplastic responses

Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex

Objective: To determine whether the intensity of transcranial magnetic stimulation (TMS) used to probe changes in corticospinal excitability influences the measured plasticity response to theta burst stimulation (TBS) of the human primary motor cortex. Methods: Motor evoked potential (MEP) input/output (I/O) curves were recorded before and following continuous TBS (cTBS) (Experiment 1; n = 18) and intermittent TBS (iTBS) (Experiment 2; n = 18). Results: The magnitude and consistency of MEP depression induced by cTBS was greatest when probed using stimulus intensities at or above 150% of resting motor threshold (RMT). In contrast, facilitation of MEPs following iTBS was strongest and most consistent at 110% of RMT. Conclusions: The plasticity response to both cTBS and iTBS is influenced by the stimulus intensity used to probe the induced changes in corticospinal excitability. Significance: The results highlight the importance of the test stimulus intensity used to assess TBS-induced changes in corticospinal excitability when interpreting neuroplasticity data, and suggest that a number of test intensities may be required to reliably probe the plasticity response