Abstract
Over the last decade, there has been an increasing number of studies combining transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). MRS provides a manner to non-invasively investigate molecular concentrations in the living brain and thus identify metabolites involved in physiological and pathological processes. Particularly the MRS-detectable metabolites glutamate, the major excitatory neurotransmitter, and gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter, are of interest when combining TMS and MRS. TMS is a non-invasive brain stimulation technique that can be applied either as a neuromodulation or neurostimulation tool, specifically targeting glutamatergic and GABAergic mechanisms. The combination of TMS and MRS can be used to evaluate alterations in brain metabolite levels following an interventional TMS protocol such as repetitive TMS (rTMS) or paired associative stimulation (PAS). MRS can also be combined with a variety of non-interventional TMS protocols to identify the interplay between brain metabolite levels and measures of excitability or receptor-mediated inhibition and facilitation. In this review, we provide an overview of studies performed in healthy and patient populations combining MRS and TMS, both as a measurement tool and as an intervention. TMS and MRS may reveal complementary and comprehensive information on glutamatergic and GABAergic neurotransmission. Potentially, connectivity changes and dedicated network interactions can be probed using the combined TMS-MRS approach. Considering the ongoing technical developments in both fields, combined studies hold future promise for investigations of brain network interactions and neurotransmission.
Highlights
Since their introduction more than 30 years ago, transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) are commonly used for studying the healthy and pathological human brain
The results indicated that gamma-aminobutyric acid (GABA) levels in the medial PFC were negatively correlated to bilateral prefrontal synchrony in the theta to gamma frequency range after cerebellar TMS, and in the theta to low beta frequency range after stimulation of the left prefrontal cortex
These results highlight that cortical plasticity is impaired in subjects with diabetes and prediabetes as compared to healthy controls, and that for subjects with diabetes, neuroplastic mechanisms can be linked with glutamate levels in M1 (Fried et al, 2019)
Summary
Since their introduction more than 30 years ago, transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) are commonly used for studying the healthy and pathological human brain. It is suggested that later parts of CSPs reflect GABAB receptor-mediated inhibition while initial parts of CSPs reflect GABAA receptor-mediated inhibition This protocol requires a sustained voluntary isometric contraction of the target muscle while at the same time a single TMS pulse is administered over the contralateral M1. With 1H-MRS the major spectral components N-acetyl aspartate (NAA), creatine, choline, and myo-inositol can be assessed in the brain in vivo, next to the combined signal of glutamate and glutamine, Glx. Assessment of e.g. glutamate and glutamine separately, gamma-aminobutyric acid (GABA), N-acetyl aspartyl glutamate (NAAG) and lactate is possible when requirements regarding magnetic field strength and/or RF pulse sequences are met. Sequence and vendor-specific issues need to be taken into account when acquiring, processing and quantifying 1HMRS data (Oz et al, 2014; Jansen et al, 2006)
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