Site-specific effects of online rTMS during a working memory task in healthy older adults

Abstract

<jats:title>Abstract</jats:title><jats:p>The process of manipulating information within working memory (WM) is central to many cognitive functions, but also declines rapidly in old age. Given the importance of WM manipulation for maintaining healthy cognition, improving this process could markedly enhance health-span in older adults. The current pre-registered study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) to enhance WM manipulation in healthy elderly adults. Online 5Hz rTMS was applied over the left lateral parietal cortex of 15 subjects to test the hypothesis that active rTMS would significantly improve performance compared to sham stimulation, and that these effects would be most pronounced in conditions with the highest cognitive demand. rTMS was applied while participants performed a delayed-response alphabetization task with two individually-titrated levels of difficulty. Sham stimulation was applied using an electrical sham coil that produced similar clicking sounds and somatosensory sensation as active stimulation but induced negligible effects on the brain. A stimulation site in left lateral parietal cortex was identified from fMRI activation maps and was targeted using individualized electric field modeling, stereotactic neuronavigation, and real-time robotic positioning, allowing optimal coil placement during the stimulation. Contrary to the <jats:italic>a priori</jats:italic> hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. These results, therefore, demonstrate engagement of cortical WM processing, but not the anticipated facilitation, and provide a prescription for future studies that may attempt to enhance memory through application of different stimulation parameters.</jats:p><jats:sec><jats:title>Highlights</jats:title><jats:list list-type="bullet"><jats:list-item><jats:p>This study is one of the first attempts to enhance WM manipulation with online rTMS</jats:p></jats:list-item><jats:list-item><jats:p>Online 5Hz rTMS and sham were applied over the left parietal cortex of older adults</jats:p></jats:list-item><jats:list-item><jats:p>Individualized fMRI and electric field modeling were used to optimize targeting</jats:p></jats:list-item><jats:list-item><jats:p>Contrary to expectations, rTMS disrupted working memory manipulation abilities</jats:p></jats:list-item><jats:list-item><jats:p>This demonstrates that parietal cortex is involved in WM and modifiable with rTMS</jats:p></jats:list-item></jats:list></jats:sec>

Fast computational optimization of TMS coil placement for individualized electric field targeting

“…Additional MRI-based head models—M1, M2, M3, and M4—were borrowed from one of our experimental studies involving E-field-based dosing ( Beynel et al, 2020 ), corresponding to subject ids S262, S263, S266, and S269, respectively. Briefly, the models were constructed using structural T1-weighted (echoplanar sequence: Voxel Size = 1 mm 3 , TR = 7.148 ms, TE = 2.704 ms, Flip Angle = 12°, FOV = 256 mm 2 , Bandwidth = 127.8 Hz/pixel), T2-weighted (echo-planar sequence with fat saturation: Voxel Size = 0.9375 × 0.9375 × 2.0 mm 3 , TR = 4 s, TE = 77.23 ms, Flip Angle = 111°, FOV = 240 mm2, Bandwidth = 129.1 Hz/pixel), and diffusion-weighted scans (Single-shot echo-planar: Voxel Size = 2 mm 3 , TR = 17 s, TE = 91.4 ms, Flip Angle = 90°, FOV = 256 mm 2 , Bandwidth = 127.8 Hz/pixel, Matrix size = 1282, B-value = 2000s/mm 2 , Diffusion directions = 26).…”

“…For each of the four additional models (M1–M4), four ROIs of various sizes where generated using the SimNIBS 3.1 TMS coil placement optimization functionality. Within subject, the center of each ROI was the same and was derived from fMRI-measured brain activity ( Beynel et al, 2020 ). The smallest ROI consisted of a single tetrahedron and had a mean effective diameter (the diameter of a sphere of the same volume) of 1.0 mm across subjects.…”

“…SimNIBS 3.1 was used to generate coil center positions on 3 cm diameter scalp region centered about the scalp position closest to the ROI CM ( Beynel et al, 2020 ). Each coil position was chosen to be approximately 1 mm apart and scalp positions where extruded outward by an amount dependent on the individual hair thickness: 3.26, 2.03, 5.55, and 2.78 mm for models M1–M4, respectively ( Beynel et al, 2020 ). The total number of coil positions was 697, 689, 689, and 697 for models M1-M4, respectively.…”

“…However, the computational requirements of the direct method limit the routine use of E-field-informed optimization of coil placement. For example, for this reason we restricted the individual model-based dosing in a recent TMS study to selecting only the coil current setting ( Beynel et al, 2020 ).…”

Older adults benefit from more widespread brain network integration during working memory

“…Older adults were screened for possible incidence of dementia, as measured by a Mattis Dementia Rating Scale-2 (DRS-2) total scaled score below 8 ( Jurica et al, 2001 ). Qualifying participants were enrolled in a 6-day TMS protocol ( Beynel et al, 2019 ; Beynel et al, in review ), but only data from the screening session (Day 1) and MRI session (Day 2) are reported here. Participants had no history of psychiatric or neurological disorders and were not using psychoactive drugs.…”