Brainsight system

Single-pulse TMS (Magstim Bistim2, Magstim Company Ltd., UK) was applied using a double-cone coil (70 mm outer diameter) over the leg area of the left primary motor cortex while the subject was standing. The optimal position (hotspot) for evoking MEP preferentially in the right SOL was determined. The hotspot was defined as the scalp position where the stimulus produced the largest motor evoked potential (MEP) amplitude in the right SOL at a given intensity [42 (link)–44 (link)]. Overall, this location was slightly to the left side of the vertex (mean of 1.2 cm left of the vertex). The hotspot was visualized on a computer through a neuronavigation system (Brainsight system; Rogue Research, Canada), by placing trackers both on the coil and on the subject. With this system, the coil was maintained at the same position throughout the experiment. The coil was held by an experimenter and positioned at around 45 degrees away from the midline over this hotspot to induce a current flow in an antero-medial direction in the targeted area [45 (link)]. The active motor threshold (aMT) was determined as the stimulus intensity at which 5 of 10 stimuli evoked a MEP bigger than 100 μV of amplitude in the contracted right SOL [31 (link)]. Stimulus intensity was set at 1.2 aMT for Part A and 0.95 aMT for Parts B and C.

The Brainsight system (Rogue Research, Montreal) was used to co-register MRI data with the location of the subject and the TMS coil. The stimulation site was defined as the posterior extent of the pars triangularis in each individual subject’s registered T1 image. A Magstim Super Rapid2 Plus1 stimulator (Magstim; Whitland, UK) was used to deliver continuous theta burst stimulation (cTBS) via a 70 mm diameter figure-eight coil. cTBS was delivered at 80% of each participant’s active motor threshold [73 (link)]. Each participant’s threshold was determined prior to the start of the experimental session using a standard up-down staircase procedure with stimulation to the motor cortex [M1]. The measured thresholds (given in units measured as the percentage of machine output from the Magstim device) for the 10 participants were 68, 60, 46, 57, 37, 36, 44, 39, 46, and 65, respectively.

All procedures were approved by either the University Committee on Animal Resources at the University of Rochester or the IACUC at the University of Minnesota. Animal procedures were also designed and conducted in compliance with the Public Health Service’s Guide for the Care and Use of Animals. All surgery was performed under anesthesia. Male rhesus macaques (Macaca mulatta) served as subjects. A small prosthesis was used to maintain stability. Animals were habituated to laboratory conditions and then trained to perform oculomotor tasks for liquid rewards. We placed a Cilux recording chamber (Crist Instruments) over the area of interest. We verified positioning by magnetic resonance imaging with the aid of a Brainsight system (Rogue Research). Animals received appropriate analgesics and antibiotics after all procedures. Throughout both behavioral and physiological recording sessions, we kept the chamber clean with regular antibiotic washes and sealed them with sterile caps.

Two male rhesus macaques (Macaca mulatta) served as subjects. Standard surgical techniques, described previously [99 (link)], were used to implant a small prosthesis for holding the head and Cilux recording chambers (Crist Instruments, Hagerstown, Maryland, United States of America). Chamber positions were verified by magnetic resonance imaging with the aid of a Brainsight system (Rogue Research, Montréal, Quebec, Canada). Neuroimaging was performed prior to surgery at the Rochester Center for Brain Imaging on a Siemens 3T MAGNETOM Trio Tim using 0.5-mm voxels.

The Brainsight system (Rogue Research) was used to co-register MRI data with the location of the subject and the TMS coil. The stimulation site was defined as the posterior extent of the pars triangularis in each individual subject’s registered T1 image. A Magstim Super Rapid² Plus¹ stimulator (Magstim) was used to deliver cTBS via a 70-mm diameter figure-eight coil. cTBS consisted of 50 Hz triplets administered every 200 ms (i.e., 5 Hz; Huang et al., 2005 (link)) for 600 total pulses. To calibrate the intensity of stimulation, cTBS was delivered at 80% of each participant’s active motor threshold (Huang et al., 2005 (link)). Each subject’s threshold was determined before the start of the experimental session using a standard up-down staircase procedure with stimulation to the motor cortex (M1). In the sham condition, the coil was held against the head at a 90° angle at the subject’s vertex to introduce a degree of induced electrical stimulation of the scalp. We administered sham at vertex to reduce the possibility that subjects could see the orientation of the coil in the sham condition, as subjects were not naive to TMS.