Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique, which has brain network-level effects in healthy individuals and is also used to treat many neurological and psychiatric conditions in which brain connectivity is believed to be abnormal. Despite the fact that rTMS is being used in a clinical setting and animal studies are increasingly identifying potential cellular and molecular mechanisms, little is known about how these mechanisms relate to clinical changes. This knowledge gap is amplified by non-overlapping approaches used in preclinical and clinical rTMS studies: preclinical studies are mostly invasive, using cellular and molecular approaches, while clinical studies are non-invasive, including functional magnetic resonance imaging (fMRI), TMS electroencephalography (EEG), positron emission tomography (PET), and behavioral measures. A non-invasive method is therefore needed in rodents to link our understanding of cellular and molecular changes to functional connectivity changes that are clinically relevant. fMRI is the technique of choice for examining both short and long term functional connectivity changes in large-scale networks and is becoming increasingly popular in animal research because of its high translatability, but, to date, there have been no reports of animal rTMS studies using this technique. This review summarizes the main studies combining different rTMS protocols with fMRI in humans, in both healthy and patient populations, providing a foundation for the design of equivalent studies in animals. We discuss the challenges of combining these two methods in animals and highlight considerations important for acquiring clinically-relevant information from combined rTMS/fMRI studies in animals. We believe that combining rTMS and fMRI in animal models will generate new knowledge in the following ways: functional connectivity changes can be explored in greater detail through complementary invasive procedures, clarifying mechanism and improving the therapeutic application of rTMS, as well as improving interpretation of fMRI data. And, in a more general context, a robust comparative approach will refine the use of animal models of specific neuropsychiatric conditions.
Highlights
An exciting approach for the treatment of neuropsychiatric conditions is to use neuronal activity itself to encourage repair and improve brain function
Transcranial magnetic stimulation (TMS) works according to the principle of electromagnetic induction: pulses of current flowing through a TMS coil generate a controllable, pulsatile magnetic field that passes into the brain unimpeded by skin, muscle or skull
Considered together, the human studies discussed in this review demonstrate the broad relevance and significance of the results from combined Repetitive transcranial magnetic stimulation (rTMS)/functional magnetic resonance imaging (fMRI) protocols
Summary
An exciting approach for the treatment of neuropsychiatric conditions is to use neuronal activity itself to encourage repair and improve brain function. Animal models have been useful in elucidating some of the mechanisms of rTMS as they allow us to perform invasive studies of molecular and genetic changes that are not ethically possible in humans These studies have been reviewed extensively elsewhere (e.g., Tang et al, 2015; Lenz and Vlachos, 2016). In this review, we suggest that fMRI will be a powerful tool amenable to visualizing and comparing rTMSinduced short and long term neural connectivity changes throughout the brain at high spatio-temporal resolutions in both humans and animals. This method could potentially help unravel the physiological processes underlying the rTMSinduced changes in the cortex and in functionally connected brain regions. We review findings from combined rTMS/fMRI studies in humans and consider potential insights from, and limitations of, using fMRI in animal rTMS studies
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