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.
Highlights
Repetitive transcranial magnetic stimulation has been shown to have therapeutic potential for a range of psychiatric conditions, including unipolar[1,2] and bipolar depression[1], schizophrenia[3], obsessive-compulsive disorder[4] and post-traumatic stress disorder[5] as well as neurological conditions such as Parkinson’s disease[6], dystonia[7], tinnitus[8], epilepsy[9] and stroke10. rTMS has shown promising results in the treatment of pain syndromes such as migraine[11] and chronic pain[12]
The default mode network (DMN) has been associated with cognitive performance and is thought to play an important role in neuroplasticity through the consolidation and maintenance of brain function15. rTMS is able to modulate the resting-state activity of the brain and DMN plasticity is sensitive to rTMS in humans but the direction and extent of this modulation depend on the rTMS protocol used[16,17,18,19,20]
The resting-state network (RSN) in the rat brain was inferred based on synchronous fluctuations of the haemodynamic signals identified by independent component analysis (ICA) of pre-stimulation resting-state functional MRI (rs-functional magnetic resonance imaging (fMRI)) data
Summary
Repetitive transcranial magnetic stimulation (rTMS) has been shown to have therapeutic potential for a range of psychiatric conditions, including unipolar[1,2] and bipolar depression[1], schizophrenia[3], obsessive-compulsive disorder[4] and post-traumatic stress disorder[5] as well as neurological conditions such as Parkinson’s disease[6], dystonia[7], tinnitus[8], epilepsy[9] and stroke10. rTMS has shown promising results in the treatment of pain syndromes such as migraine[11] and chronic pain[12]. Each animal was scanned at four timepoints, enabling the investigation of the reproducibility of the group-ICA results over time and between subjects using pre-stimulation rs-fMRI data (Fig. 4A).
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