Resting-state fMRI study of brain activation using low-intensity repetitive transcranial magnetic stimulation in rats

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used to treat many neuropsychiatric conditions. However, the mechanisms underlying its mode of action are still unclear. This is the first rodent study using resting-state functional MRI (rs-fMRI) to examine low-intensity (LI) rTMS effects, in an effort to provide a direct means of comparison between rodent and human studies. Using anaesthetised Sprague-Dawley rats, rs-fMRI data were acquired before and after control or LI-rTMS at 1 Hz, 10 Hz, continuous theta burst stimulation (cTBS) or biomimetic high-frequency stimulation (BHFS). Independent component analysis revealed LI-rTMS-induced changes in the resting-state networks (RSN): (i) in the somatosensory cortex, the synchrony of resting activity decreased ipsilaterally following 10 Hz and bilaterally following 1 Hz stimulation and BHFS, and increased ipsilaterally following cTBS; (ii) the motor cortex showed bilateral changes following 1 Hz and 10 Hz stimulation, a contralateral decrease in synchrony following BHFS, and an ipsilateral increase following cTBS; and (iii) hippocampal synchrony decreased ipsilaterally following 10 Hz, and bilaterally following 1 Hz stimulation and BHFS. The present findings demonstrate that LI-rTMS modulates functional links within the rat RSN with frequency-specific outcomes, and the observed changes are similar to those described in humans following rTMS.

Validation of Chronic Restraint Stress Model in Young Adult Rats for the Study of Depression Using Longitudinal Multimodal MR Imaging

“…All MR images were acquired with a Bruker Biospec 94/30 small animal MRI system operating at 9.4 T (400 MHz, H-1), with an Avance III HD console, BGA-12SHP imaging gradients, a 72-mm (inner diameter) volume transmit coil and a rat brain surface quadrature receive coil using the imaging protocol as detailed in Seewoo et al (2018 , 2019 ). The acquisition protocol included the following sequences: (1) multislice 2D RARE (rapid acquisition with relaxation enhancement) sequence for three T2-weighted anatomic scans (TR = 2500 ms, TE = 33 ms, matrix = 280 × 280, pixel size = 0.1 × 0.1 mm 2 , 21 coronal and axial slices, 20 sagittal slices, thickness = 1 mm); (2) single-shot gradient-echo echoplanar imaging (TR = 1500 ms, TE = 11 ms, matrix = 94 × 70, pixel size = 0.3 × 0.3 mm 2 , 21 coronal slices, thickness = 1 mm, flip angle = 90°, 300 volumes, automatic ghost correction order = 1, receiver bandwidth = 300 kHz) for resting-state; and (3) point-resolved spectroscopy (PRESS) sequence with one 90° and two 180° pulses and water suppression for 1 H-MRS (TE = 16 ms, TR = 2500 ms) with 64 averages with a 3.5 × 2 × 6 mm 3 voxel placed over the left sensorimotor cortex ( Fig.…”

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

“…Reasons for how rTMS induces therapeutic effects in various neurological disorders remain unclear; however, a number of preclinical studies have identified mechanisms that could underlie the long-term effects. These mechanisms include alterations to neuron excitability (Sun et al, 2011;Hoppenrath et al, 2016;Tang et al, 2016) and Hebbiantype strengthening of synapses (Vlachos et al, 2012;Lenz et al, 2015), as well as alterations to gene expression (Ikeda et al, 2005;Grehl et al, 2015), trophic factors necessary for neuroplasticity (Gersner et al, 2011;Rodger et al, 2012;Makowiecki et al, 2014), activity within brain regions beyond the induced electrical field (Aydin-Abidin et al, 2008;Seewoo et al, 2018Seewoo et al, , 2019, and even changes to non-neuronal cells, which may contribute to plastic events (Clarke et al, 2017a,b;Cullen et al, 2019).…”

“…The relevance of animal studies in understanding rTMS effects in humans has recently been highlighted by neuroimaging studies showing that rTMS can induce similar changes in functional connectivity in rats and in humans (Cocchi et al, 2016;Seewoo et al, 2018Seewoo et al, , 2019. More specifically, chronic rTMS in healthy rats was associated with changes to addiction-related networks such as the cortical-striatal-thalamic and basal-ganglia networks, with chronic HF-rTMS potentiating interoceptive/default mode network connectivity and attenuating connectivity in the salience network (Seewoo et al, 2019).…”

Validation of chronic restraint stress model in rats for the study of depression using longitudinal multimodal MR imaging

“…All MR images were acquired with a Bruker Biospec 94/30 small animal MRI system operating at 9.4 T (400 MHz, H-1), with an Avance III HD console, BGA-12SHP imaging gradients, a 72 mm (inner diameter) volume transmit coil and a rat brain surface quadrature receive coil using the imaging protocol as described in detail in Seewoo et al (2018;. Briefly, the acquisition protocol included the following sequences: 1) multi-slice 2D RARE (rapid acquisition with relaxation enhancement) sequence for three T2-weighted anatomical scans (TR=2500 ms, TE=33 ms, matrix=280x280, pixel size=0.1x0.1 mm 2 , 21 coronal and axial slices, 20 sagittal slices, thickness=1 mm); 2) single-shot gradient echo EPI (TR=1500 ms, TE=11 ms, matrix=94x70, pixel size=0.3x0.3 mm 2 , 21 coronal slices, thickness=1 mm, flip angle=90°, 300 volumes, automatic ghost correction order = 1, receiver bandwidth = 300 kHz) for resting-state; and 3) pointresolved spectroscopy (PRESS) sequence with one 90° and two 180° pulses and water suppression for 1 H-MRS (TE=16 ms, TR=2500 ms) with 64 averages with a 3.5x2×6 mm 3 voxel placed over the left sensorimotor cortex (Fig.…”

“…All further pre-processing and analyses were performed using FSL v5.0.10 (Functional MRI of the Brain (FMRIB) Software Library) (Jenkinson et al, 2012). Single-session independent component analysis (ICA) as implemented in FSL/MELODIC (Multivariate Exploratory Linear Decomposition into Independent Components) (Beckmann et al, 2005) was used to de-noise the data (detailed in Seewoo et al, 2018). The de-noised rs-fMRI images were then coregistered to their respective T2-weighted coronal images using six-parameter rigid body registration using FSL/FLIRT (Linear Image Registration Tool) (Jenkinson and Smith, 2001;Jenkinson et al, 2002) and normalised to a Sprague-Dawley brain atlas (Papp et al, 2014;Kjonigsen et al, 2015;Sergejeva et al, 2015) with nine degrees of freedom 'traditional' registration.…”