Graduate Student Seminar Series
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Location: HS610 – 155 College St, Room 610
Presentation Title: Real-time evolution of the fMRI response to transcranial photobiomodulation in the human brain
Abstract:
Introduction
Transcranial photobiomodulation (tPBM) uses near-infrared light to stimulate neural tissue1. Recent research on tPBM reports significant potential for applications in the treatment of neurological conditions such as neurodegenerative disorders, neurotrauma, and neuropsychiatric conditions2-5, as well as producing improvements in emotional and cognitive function in healthy individuals6-7. However, the exact underlying mechanism of action is still unclear; little is known about the localization of the brain response to the site of stimulation and how it spreads and dissipates depending on dose parameters.
Methods
14 healthy adults (7M, aged 24.4 ± 3.7 years) were scanned on a Siemens Prisma 3T system while receiving pulsed tPBM via single laser to the right forehead (spot size 1cm). The tPBM protocol included a 4-minute stimulation period with equivalent pre-stimulus and post-stimulus baseline blocks. The laser was pulsed at two frequencies (10 and 40Hz), with two wavelengths (808 and 1064nm) and three optical power densities (100, 150 and 200 mW/cm2). The brain response was measured using a dual-echo pseudo-continuous arterial-spin labeling sequence (TR=4.5s, TE1=9.4ms, TE2=30ms, voxel size=2x2x2 mm). Surround averaging of the TE2 data was used to generate the blood-oxygenation-level-dependent (BOLD) signal.
Brain extraction, motion & distortion correction, slice timing, and bandpass filtering to Hz were performed using FSL. Rapid time delay analysis was then applied using Rapidtide8 (v2.9.6), with the stimulus timing vector as the probe regressor9. The cross-correlation maps with the probe were thresholded at p 0.85 density were used to characterize the dose dependence of the spatial fMRI response. Group-averaged time courses were also generated from the voxels demonstrating the maximum cross-correlations (p<0.05).
To quantify the temporal evolution of the fMRI response, significant voxels per time window were counted and then plotted, and voxel-count decline fitted to an exponential function. Along with the peak voxel count (V), the time till peak voxel count (Tp, to represent the response ramp-up) and the exponential time constant (τ, to represent the ramp-down) and submitted to a stepwise linear mixed-effects model (LME), with the predictor variables being wavelength, frequency, and power density.
Results
Based on the density maps in Fig. 1, the brain response is not confined to the site of stimulation. Rather, it quickly spreads across the anterior brain. 10 Hz pulsation produced a larger spatial extent in the BOLD response, with the use of 808 nm at 10 Hz resulting in the largest extent among the four combinations. However, while 1064 nm at 10 Hz produced the lowest peak response, the 1064-nm-40-Hz combination produced the highest % BOLD amplitude. The bulk of the common responding voxels disappear by ~20 s irrespective of parameter setting. The stepwise LME of the parameters of temporal evolution revealed that higher power resulted in slower decline of the response voxel count, and higher frequency resulted in a faster decline (higher τ, p<0.05 and shorter τ, p<0.05, respectively).
Conclusion
In this work, we illustrate how quickly the tPBM response spreads from the stimulation site and how quickly it subsides post stimulation. We also show that the response is predominantly in the frontal brain regions, in accordance with a forehead stimulation, but that different regions respond at different lags. Furthermore, 808 nm at 10 Hz elicited the strongest and most consistent response across different subjects. This work lays the foundation for a better understanding of the mechanisms of action of tPBM.
Supervisor Name: Jean Chen
Year of Study: 2
Program of Study: MASc
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