R. Bathe-Peters

Nonphysiological factors in navigated TMS studies; Confounding covariates and valid intracortical estimates

Brain stimulation is used to induce transient alterations of neural excitability to probe or modify brain function. For example, single‐pulse transcranial magnetic stimulation (TMS) of the motor cortex can probe corticospinal excitability (CSE). Yet, CSE measurements are confounded by a high level of variability. This variability is due to physical and physiological factors. Navigated TMS (nTMS) systems can record physical parameters of the TMS coil (tilt, location, and orientation) and some also estimate intracortical electric fields (EFs) on a trial‐by‐trial basis. Thus, these parameters can be partitioned with stepwise regression.

Evolution of Premotor Cortical Excitability after Cathodal Inhibition of the Primary Motor Cortex: A Sham-Controlled Serial Navigated TMS Study

Background Premotor cortical regions (PMC) play an important role in the orchestration of motor function, yet their role in compensatory mechanisms in a disturbed motor system is largely unclear. Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex (M1). Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion. Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1. These studies have contributed to our understanding of how M1 responds to changes in PMC neural activity. Yet, the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear. Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation (tDCS). Purpose The primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance. Hypothesis Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability. Methods We enrolled 16 healthy participants in this randomized, double-blind, sham-controlled, crossover design study. All participants underwent navigated transcranial magnetic stimulation (nTMS) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical, intracortical and interhemispheric excitability. Cortical M1 excitability was inhibited using cathodal tDCS. Finger-tapping speeds were used to examine motor function. Results Cathodal tDCS successfully reduced M1 excitability and motor performance speed. PMC excitability was increased for longer and was the only significant predictor of motor performance. Conclusion The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance.

P20.17 Progressive enhancement of alpha activity and visual function in patients with optic neuropathy; a two-week non-invasive alternating current stimulation study

half of the people surviving stroke remain with some form of UL impairment. Robot Therapy (RT) is one technique that can increase the intensity of rehabilitation and evidence shows that robot-assisted arm training results in improved shortand long-term arm strength and function of people with stroke. RT has also been combined with a non-invasive method of brain stimulation, transcranial Direct Current Stimulation (tDCS). The pilot study by Hesse et al. (2007) suggests that using both RT and tDCS results in short-term UL motor recovery of people with sub-acute stroke however, long-term and neurophysiological measurements were not involved in this study. Main objective: To develop a protocol exploring the effectiveness and shortand long-term neural changes of tDCS and robot therapy on UL impairment and function of people with sub-acute stroke. Methods: A systematic literature review was carried out investigating different methodologies used for applying tDCS and RT, leading to the finalised protocol. Results: A pilot, double-blinded randomised controlled trial will be carried out involving two groups: (1) Armeo RT and active tDCS, and (2) Armeo RT and sham tDCS with 20 participants with sub-acute stroke in each group. Active or sham tDCS will be delivered before RT. In total, participants will receive 18 hours of RT and tDCS, spread out over 8 weeks. Clinical and neurophysiological measures using Transcranial Magnetic Stimulation will be utilised preand post-intervention and at 3 month follow-up. Conclusions: Research into non-invasive brain stimulation and RT seems promising but to translate research findings into clinical stroke practice, further research is needed. In the upcoming months, the aforementioned trial will be initiated which will add to the body of knowledge of neurorehabilitation research.

Force Increase in a Repetitive Motor Task Inducing Motor Fatigue

Abstract To evaluate task induced motor fatigue in a well-established finger tapping task, we analyzed tapping parameters and included the time course of measures of force. We hypothesized that a decline in tapping force would reflect task induced motor fatigue, defined by a lengthening of inter-tap intervals (ITI). A secondary aim was to investigate the reliability of tapping data acquisition with the force sensor. Results show that, as expected, tapping speed decreased linearly over time, due to both an increase of ITI and tap duration. In contrast, tapping force increased non-linearly over time and was uncorrelated to changes in tapping speed. Force data could serve as a measure to characterize task induced motor fatigue. Force sensors can assess a decline in tapping speed as well as an independent increase of tapping force. We argue that the increase of force reflects central compensation, i.e. perception of fatigue, due to an increase in task effort and difficulty.

P1066: Movement preparation requires early activation of the dorsal premotor area

before and after the exercise on day 1 (T0, T1) and after the exercise on day 5 (T2). Basketball players attended only to T0 and T1. Results: In FCR of the sedentary group (Fig. 1, amplitude ratios, blue: T0, red: T1, green: T2, bars: standard deviations), there were less short latency afferent inhibition and higher facilitation at T1 (statistically significant at ISI 35 and 50 ms). This effect decreased at T2 despite the increased success rate. Basketball players did not show a facilitation as high as that found in the sedentary group. Conclusion: Short term exercises lead to SMI changes which may function in the early phase of gaining the ability. Continued training provided higher success while the electrophysiological changes was decreasing, possibly by the conversion of the learning process into different mechanisms. Exercising already gained abilities do not produce similar SMI changes.

P 13. Intersession reliability of cortical motor maps with navigated transcranial magnetic stimulation

Introduction Navigated transcranial magnetic stimulation (nTMS) is a non-invasive highly effective tool for mapping individual muscle representations in the motor cortex Julkunen et al., 2009 , Picht et al., 2011 . Optical navigation and model based estimates of intracortical target sites and stimulation strength suggest that nTMS should provide spatially more precise cartography than using external landmarks for defining a motor ‘hot-spot’. The remaining outstanding challenges are (a) a high inter-and intra-subject variability of motor evoked potentials (MEP) Schmidt et al., 2009 , Brasil-Neto et al., 1992 , (b) the extent to which anatomical mapping relative to the underlying gyrification is preferable and (c) hemispheric functional asymmetries possibly reflecting functional “lateralization”. These factors are particularly relevant in a clinical context, where typically cartography will be used with single pulses per stimulation location. Further, the definition of a representation “area” is strongly confounded by the variability of “fringe neurons” or overlapping cortical representations (Schieber and Hibbard, 1993) . Objectives The aim was to study the extent to which single pulse cartography can assure reproducible results. In the present analysis we focus on the concept of the “hot-spot”, i.e. point of maximum MEP and Center of Gravity (CoG). Materials and Methods 15 subjects were examined in two sessions by two different researchers. Stimulation was performed using a computer based navigated TMS system with a figure-of-eight-coil (eXimia, Nextim Ltd., Helsinki, Finland). Mapping of the FDI over both hemispheres was performed with perpendicular (fine) and changing (random) coil orientation with an average of 79 (±35.91) stimuli at 110% resting motor threshold. Margins were defined as scalp locations where a stimulus resulted in an MEP (Mortifee et al., 1994) . Results Stimulus location for the FDI-“hot-spot” in the dominant hemisphere showed a high intersession correlation (ICC: 81–87%). In the non-dominant hemisphere the ICC was lower (45–73%). There was no significant difference in ICC using intracortical instead of scalp stimulus location. Weighted “hot-spots” as expressed by the CoG showed a very high intersession reliability (ICC: 84–88%), the side of maximum MEP a rather poor intersession reliability (ICC: 9–72%). Perpendicular mapping was associated with significant higher test–retest correlation than random mapping (ICC for random mapping 22–38%). Conclusion • Stimulus locations (“hot-spots”) in the dominant hemisphere are more precise than in the non-dominant hemisphere. • Intracortical locations are not superior to scalp location for “hot-spot”-measurements. • Weighted “hot-spots” are more precise than maximal MEPs for “hot-spot”-definition and inter-rater reproducible. • Perpendicular mapping is clearly spatially more accurate than random mapping.