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Reaching is a fundamental skill that allows humans to interact with the environment. Several studies have aimed to characterize reaching behavior using a variety of methodologies. This paper offers an open-source application of transcranial magnetic stimulation to assess the state of corticospinal excitability in humans during reaching task performance.
Reaching is a widely studied behavior in motor physiology and neuroscience research. While reaching has been examined using a variety of behavioral manipulations, there remain significant gaps in the understanding of the neural processes involved in reach planning, execution, and control. The novel approach described here combines a two-dimensional reaching task with transcranial magnetic stimulation (TMS) and concurrent electromyography (EMG) recording from multiple muscles. This method allows for the noninvasive detection of corticospinal activity at precise time points during the unfolding of reaching movements. The example task code includes a delayed response reaching task with two possible targets displayed ± 45° off the midline. Single pulse TMS is delivered on the majority of task trials, either at the onset of the preparatory cue (baseline) or 100 ms prior to the imperative cue (delay). This sample design is suitable for investigating changes in corticospinal excitability during reach preparation. The sample code also includes a visuomotor perturbation (i.e., cursor rotation of ± 20°) to investigate the effects of adaptation on corticospinal excitability during reach preparation. The task parameters and TMS delivery can be adjusted to address specific hypotheses about the state of the motor system during reaching behavior. In the initial implementation, motor evoked potentials (MEPs) were successfully elicited on 83% of TMS trials, and reach trajectories were recorded on all trials.
Goal-directed reaching is a fundamental motor behavior that allows humans to interact with and manipulate the external environment. The study of reaching in the fields of motor physiology, psychology, and neuroscience has produced rich and extensive literature that includes a variety of methodologies. Early studies of reaching used direct neural recordings in non-human primates to investigate neural activity at the level of single neurons1,2. More recent studies have investigated reaching using behavioral paradigms that employ sensorimotor adaptation to explore the nature of motor learning and control3,4,5. Such behavioral tasks combined with functional magnetic resonance imaging and electroencephalography can measure whole brain activity during reaching in humans6,7. Other studies have applied online TMS to investigate various features of reach preparation and execution8,9,10,11,12,13,14. However, there remains a need for an open-source and flexible approach that combines the behavioral assessment of reaching with TMS. While the utility of combining TMS with behavioral protocols is very well established15, here, we specifically examine the application of TMS within the context of reaching using an open-source approach. This is novel in that other groups who have published using this combination of methods have not made their tools readily available, prohibiting direct replication. This open-source approach facilitates replication, data sharing, and the possibility of multi-site studies. Additionally, should others wish to pursue novel research questions with similar tools, the open-source code can act as a launch pad for innovation, as it is readily adaptable.
TMS offers a noninvasive means of probing the motor system at precisely controlled time points16. When applied over the primary motor cortex (M1), TMS can elicit a measurable deflection in the electromyogram of a targeted muscle. The amplitude of this voltage wave, known as the motor evoked potential (MEP), provides an index of the momentary excitability state of the corticospinal (CS) pathway-a resultant analog of all excitatory and inhibitory influences on the CS pathway17. In addition to providing a reliable within-subject measurement of intrinsic CS excitability, TMS can be combined with other behavioral or kinematic metrics to investigate the relationships between CS activity and behavior in a temporally precise manner. Many studies have utilized a combination of TMS and electromyography (EMG) to address a variety of questions about the motor system, particularly since this combination of methods makes it possible to investigate MEPs under a vast array of behavioral conditions15. One area where this has proven particularly useful is in the study of action preparation, most often through the study of single-joint movements18. However, there are comparatively fewer TMS studies of naturalistic multi-joint movements such as reaching.
The current goal was to design a delayed-response reaching task that includes behavioral kinematics, online single-pulse TMS administration, and simultaneous EMG recording from multiple muscles. The task includes a two-dimensional point-to-point reaching paradigm with online visual feedback using a horizontally oriented monitor such that visual feedback matches reach trajectories (i.e., a 1:1 relationship during veridical feedback and no transformation between visual feedback and motion). The current design also includes a set of trials with a visuomotor perturbation. In the provided example, this is a 20° rotational shift in the cursor feedback. Previous studies have used a similar reaching paradigm to address questions about the mechanisms and computations associated with sensorimotor adaptation19,20,21,22,23,24,25. Furthermore, this approach makes it possible to assess motor system excitability dynamics at precise time points during online motor learning.
Because reaching has proven to be a fruitful behavior for investigating learning/adaptation, assessing CS excitability in the context of this behavior has enormous potential to shed light on the neural substrates involved in these behaviors. These may include local inhibitory influences, changes in tuning properties, the timing of neural events, etc., as have been established in non-human primate research. However, these features have been more difficult to quantify in humans and clinical populations. Neural dynamics can also be investigated in the absence of overt movement in humans using the combined TMS and EMG approach (i.e., during the preparation of movement or at rest).
The tools presented are open-source, and the code is easily adaptable. This novel paradigm will produce important insights into the mechanisms involved in the preparation, execution, termination, and adaptation of reaching movements. Moreover, this combination of methods has the potential to uncover relationships between electrophysiology and reaching behavior in humans.
All methods detailed here were performed in compliance with IRB protocol and approval (University of Oregon IRB protocol number 10182017.017). Informed consent was obtained from all subjects.
1. Reaching apparatus
2. Machine interfaces
3. Photodiode sensor
4. Software
5. Participant screening and informed consent
6. Subject setup
7. Transcranial magnetic stimulation
8. Reaching task setup
9. Task design
10. TMS administration
Successful execution of the described methods includes the recording of tablet data, EMG traces, and reliable elicitation of MEPs. An experiment was completed that included 270 test trials with TMS delivered on 4/5 of the trials (216 trials).
Data were collected from 16 participants (eight females; eight males) aged 25 ± 10 years, all of whom self-reported as right-handed. We assessed the effectiveness of the visual perturbation on behavioral performance by deriving a learning function fo...
The methods outlined above offer a novel approach to studying motor preparation in the context of reaching behaviors. Although reaching represents a popular model task in the study of motor control and learning, there is a need for precisely evaluating the CS dynamics associated with reaching behavior. TMS offers a noninvasive, temporally precise method of capturing CS activity at discrete time points during reaching. The approach described here combines two independent subfields-TMS and reaching-into a ...
All authors declare that there are no conflicts of interest
This research was made possible in part by the generous funding of the Knight Campus Undergraduate Scholars program and the Phil and Penny Knight Foundation
Name | Company | Catalog Number | Comments |
2-Port Native PCI Express | StarTech.com | RS232 Card with 16950 UART | Must be compatible with desktop computer |
Adjustable 80-20 aluminum frame | any | ||
Alcohol prep pads | any | EMG preparation | |
Bagnoli Bipolar Electrodes | Delsys | DE 2.1 | |
Bagnoli Reference Electrode | Delsys | USX2000 | 2” (5cm) Round |
Bagnoli-8 EMG System | Delsys | ||
Chair | any | ||
Computer monitor for EMG/TMS | n/a | ||
Desk | any | ||
Desktop Computer | Dell | xps 8930 | RAM: 16 GB, Storage: 1TB, Graphics: 1060 6GB |
EMG electrodes | Delsys | Sensor Adhesive Interface | |
Fine grain sandpaper | any | EMG preparation | |
Graphics tablet | Wacom | Intuos-4 XL | |
Handle of paint roller | any | to be used as stylus handle, hollowed out center must be large enough for stylus to sit securely inside | |
Medical tape | any | To secure EMG electrodes | |
PCI-6220 card DAQ | National Instruments | To interface EMG system | |
Photodiode Sensor | Vishay | BPW21R | To record timing of task events into EMG trace. |
Rear TMS port | Magstim | Included with TMS machine | |
Right-handed polyethylene glove | any | Cut out thumb and index finger of glove to expose FDI muscle | |
Sensory Adhesive Interface, 2-slot | Delsys | SC-F01 | |
Stylus | Wacom | Intuos-4 grip pen | |
Tablet-to-Computer USB cable | any | Included in Tablet purchase | |
Task Monitor | Asus | VG248 | |
TMS coil | Magstim | D70 Remote Coil | 7cm diameter, figure-of-eight coil |
TMS machine | Magstim | 200-2 | |
TMS-to-Computer DB9 cable | any | Connects to PCIe Serial Card | |
Velcro | any | To be placed on glove and stylus handle |
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