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Effects of bifrontal transcranial direct current stimulation on brain metabolites and clinical outcome - investigations using multimodal imaging methods
Effects of bifrontal transcranial direct current stimulation on brain metabolites and clinical outcome - investigations using multimodal imaging methods
Electrical stimulation for the treatment of patients has been already used for centuries starting with experiences of pain relief using an electrical torpedo fish (Sarmiento et al., 2016), continuing with the investigation of electrical stimulation of muscle cells by Luigi Galvani and finally using electrical stimulation to improve mood of depressed patients by the end of the 18th century (Sarmiento et al., 2016). By the mid of the 20th century scientists started to systematically explore electrical stimulation applied to the cortex of animals modulating neuronal activity (Isitan et al., 2020). Inspired by these results, transcranial electrical stimulation (TES) of the human brain was first investigated using single, brief high-voltage electrical shocks, which generated motor-evoked potentials (MEP), yet were highly uncomfortable (Zago et al., 2021). Later, new stimulation protocols were investigated, whereas the short, high-voltage shocks were replaced by low-intensity continuous direct currents named transcranial direct current stimulation (tDCS). TDCS is a safe, easy to use, easy portable and cost-effective non-invasive brain stimulation (NIBS) technique (A. R. Brunoni, Ferrucci, et al., 2012; A. R. Brunoni, Nitsche, et al., 2012). It does not directly stimulate neurons but shifts the resting membrane potential of neurons to a more depolarized state, hence, increasing the probability of generating an action potential, or to a more hyperpolarized state, hence, decreasing the probability of generating an action potential (Chase et al., 2020). Reported tDCS effects on the brain have been variable and mixed. To gain more knowledge about de– and hyperpolarization of neurons tDCS was investigated in combination with numerous imaging methods such as magnetic resonance imaging (MRI). MRI is a popular technique in neuroscience enabling non-invasive investigations of brain structures, metabolism and functions in both animals and humans. With the technical progress in medicine, a basic imaging technique has become highly relevant for clinical research named magnetic resonance spectroscopy (MRS). MRS or nuclear magnetic resonance (NMR) spectroscopy (van der Graaf, 2010) allows to non-invasively measure brain metabolites in vivo. This technique has been long known as an analytical method in chemistry identifying the structures of molecules. Due to the improvement of MRI systems with higher magnetic fields such as 3 and 7 Tesla (Robitaille & Abduljalil, 1998; Schild, 2005), the measurement of metabolite concentrations using MRS was established (van der Graaf, 2010). This opportunity opened a new field of research investigating the direct molecular effect of tDCS stimulation on the change of brain metabolite concentrations, amongst others the two highly prominent neurotransmitters for excitation and inhibition, glutamate (Glu) and gamma aminobutric acid (GABA). As the tDCS current reaching neurons is mostly diminished through the scalp (Chase et al., 2020), electric field (e-field) simulations not only give insights in the current strength reaching the neuronal cells, but also its distribution based on individual anatomical images (MacKenbach et al., 2020). The combination of these methods has the potential to open a new era of precision medicine and more targeted treatment.
tDCS, MRS, electrical field simulation, depression, MRI
Erhardt, Eva
2024
Englisch
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Erhardt, Eva (2024): Effects of bifrontal transcranial direct current stimulation on brain metabolites and clinical outcome - investigations using multimodal imaging methods. Dissertation, LMU München: Medizinische Fakultät
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Abstract

Electrical stimulation for the treatment of patients has been already used for centuries starting with experiences of pain relief using an electrical torpedo fish (Sarmiento et al., 2016), continuing with the investigation of electrical stimulation of muscle cells by Luigi Galvani and finally using electrical stimulation to improve mood of depressed patients by the end of the 18th century (Sarmiento et al., 2016). By the mid of the 20th century scientists started to systematically explore electrical stimulation applied to the cortex of animals modulating neuronal activity (Isitan et al., 2020). Inspired by these results, transcranial electrical stimulation (TES) of the human brain was first investigated using single, brief high-voltage electrical shocks, which generated motor-evoked potentials (MEP), yet were highly uncomfortable (Zago et al., 2021). Later, new stimulation protocols were investigated, whereas the short, high-voltage shocks were replaced by low-intensity continuous direct currents named transcranial direct current stimulation (tDCS). TDCS is a safe, easy to use, easy portable and cost-effective non-invasive brain stimulation (NIBS) technique (A. R. Brunoni, Ferrucci, et al., 2012; A. R. Brunoni, Nitsche, et al., 2012). It does not directly stimulate neurons but shifts the resting membrane potential of neurons to a more depolarized state, hence, increasing the probability of generating an action potential, or to a more hyperpolarized state, hence, decreasing the probability of generating an action potential (Chase et al., 2020). Reported tDCS effects on the brain have been variable and mixed. To gain more knowledge about de– and hyperpolarization of neurons tDCS was investigated in combination with numerous imaging methods such as magnetic resonance imaging (MRI). MRI is a popular technique in neuroscience enabling non-invasive investigations of brain structures, metabolism and functions in both animals and humans. With the technical progress in medicine, a basic imaging technique has become highly relevant for clinical research named magnetic resonance spectroscopy (MRS). MRS or nuclear magnetic resonance (NMR) spectroscopy (van der Graaf, 2010) allows to non-invasively measure brain metabolites in vivo. This technique has been long known as an analytical method in chemistry identifying the structures of molecules. Due to the improvement of MRI systems with higher magnetic fields such as 3 and 7 Tesla (Robitaille & Abduljalil, 1998; Schild, 2005), the measurement of metabolite concentrations using MRS was established (van der Graaf, 2010). This opportunity opened a new field of research investigating the direct molecular effect of tDCS stimulation on the change of brain metabolite concentrations, amongst others the two highly prominent neurotransmitters for excitation and inhibition, glutamate (Glu) and gamma aminobutric acid (GABA). As the tDCS current reaching neurons is mostly diminished through the scalp (Chase et al., 2020), electric field (e-field) simulations not only give insights in the current strength reaching the neuronal cells, but also its distribution based on individual anatomical images (MacKenbach et al., 2020). The combination of these methods has the potential to open a new era of precision medicine and more targeted treatment.