Ilenia Paparella, Paolo Cardone, Benedetta Zanichelli, Laurent Lamalle, Fabienne Collette, Siya Sherif, Mikhail Zubkov, William T. Clarke, Charlotte J. Stagg, Pierre Maquet, Gilles Vandewalle
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Here we collected ultra-high-field 7 Tesla MRS and transcranial magnetic stimulation coupled with high-density electroencephalography (TMS-hdEEG) from the motor cortex of 20 healthy participants (age 23.95 ± 6.4 years), while they were at rest. We first applied a neural mass model (NMM) to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of parametric empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS. Our work will help fulfil the promises of MRS-GABA, enhancing our understanding of human behaviour, brain physiology and pathophysiology.\n\n <figure>\n <div><picture>\n <source></source></picture><p></p>\n </div>\n </figure>\n </div>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>GABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke.</li>\n \n <li>Quantification of GABA in the human brain is typically obtained by magnetic resonance spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated.</li>\n \n <li>By using a biophysical neural mass model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 9","pages":"2821-2838"},"PeriodicalIF":4.7000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"7 Tesla magnetic resonance spectroscopy estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex\",\"authors\":\"Ilenia Paparella, Paolo Cardone, Benedetta Zanichelli, Laurent Lamalle, Fabienne Collette, Siya Sherif, Mikhail Zubkov, William T. Clarke, Charlotte J. 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7 Tesla magnetic resonance spectroscopy estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex
GABAergic neurotransmission within the cortex plays a key role in learning and is altered in several brain diseases. Quantification of bulk GABA in the human brain is typically obtained by magnetic resonance spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. A recent mathematical simulation contends that MRS detects extrasynaptic GABA, mediating tonic inhibition. Nevertheless, no empirical data have yet confirmed this hypothesis. Here we collected ultra-high-field 7 Tesla MRS and transcranial magnetic stimulation coupled with high-density electroencephalography (TMS-hdEEG) from the motor cortex of 20 healthy participants (age 23.95 ± 6.4 years), while they were at rest. We first applied a neural mass model (NMM) to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of parametric empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS. Our work will help fulfil the promises of MRS-GABA, enhancing our understanding of human behaviour, brain physiology and pathophysiology.
Key points
GABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke.
Quantification of GABA in the human brain is typically obtained by magnetic resonance spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated.
By using a biophysical neural mass model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex.
期刊介绍：
The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew.
The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.
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