Dídac Vidal-Piñeiro1, Pablo Martín-Trias1, Carles Falcón2, Núria Bargalló3, Imma C Clemente4, Josep Valls-Solé5, Carme Junqué6, Alvaro Pascual-Leone7, David Bartrés-Faz8. 1. Department of Psychiatry and Clinical Psychobiology, Faculty of Medicine, University of Barcelona, Spain. 2. Medical Imaging Group, University of Barcelona, CIBER-BBN, Spain. 3. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Neuroradiology Section, Radiology Service, Centre de Diagnòstic per la Imatge, Hospital Clinic de Barcelona, Spain. 4. Department of Psychiatry and Clinical Psychobiology, Faculty of Psychology, University of Barcelona, Spain. 5. EMG Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona, Spain. 6. Department of Psychiatry and Clinical Psychobiology, Faculty of Medicine, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain. 7. Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Institut Universitari de Neurorehabilitació Guttmann, Universitat Autònoma de Barcelona, Badalona, Spain. 8. Department of Psychiatry and Clinical Psychobiology, Faculty of Medicine, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain. Electronic address: dbartres@ub.edu.
Abstract
BACKGROUND: The Default Mode Network (DMN) is severely compromised in several psychiatric and neurodegenerative disorders where plasticity alterations are observed. Glutamate and GABA are the major excitatory and inhibitory brain neurotransmitters respectively and are strongly related to plasticity responses and large-scale network expression. OBJECTIVE: To investigate whether regional Glx (Glutamate + Glutamine) and GABA could be modulated within the DMN after experimentally-controlled induction of plasticity and to study the effect of intrinsic connectivity over brain responses to stimulation. METHODS: We applied individually-guided neuronavigated Theta Burst Stimulation (TBS) to the left inferior parietal lobe (IPL) in-between two magnetic resonance spectroscopy (MRS) acquisitions to 36 young subjects. A resting-state fMRI sequence was also acquired before stimulation. RESULTS: After intermittent TBS, distal GABA increases in posteromedial DMN areas were observed. Instead, no significant changes were detected locally, in left IPL areas. Neurotransmitter modulation in posteromedial areas was related to baseline fMRI connectivity between this region and the TBS-targeted area. CONCLUSIONS: The prediction of neurotransmitter modulation by connectivity highlights the relevance of connectivity patterns to understand brain responses to plasticity-inducing protocols. The ability to modulate GABA in a key core of the DMN by means of TBS may open new avenues to evaluate plasticity mechanisms in a key area for major neurodegenerative and psychiatric conditions.
BACKGROUND: The Default Mode Network (DMN) is severely compromised in several psychiatric and neurodegenerative disorders where plasticity alterations are observed. Glutamate and GABA are the major excitatory and inhibitory brain neurotransmitters respectively and are strongly related to plasticity responses and large-scale network expression. OBJECTIVE: To investigate whether regional Glx (Glutamate + Glutamine) and GABA could be modulated within the DMN after experimentally-controlled induction of plasticity and to study the effect of intrinsic connectivity over brain responses to stimulation. METHODS: We applied individually-guided neuronavigated Theta Burst Stimulation (TBS) to the left inferior parietal lobe (IPL) in-between two magnetic resonance spectroscopy (MRS) acquisitions to 36 young subjects. A resting-state fMRI sequence was also acquired before stimulation. RESULTS: After intermittent TBS, distal GABA increases in posteromedial DMN areas were observed. Instead, no significant changes were detected locally, in left IPL areas. Neurotransmitter modulation in posteromedial areas was related to baseline fMRI connectivity between this region and the TBS-targeted area. CONCLUSIONS: The prediction of neurotransmitter modulation by connectivity highlights the relevance of connectivity patterns to understand brain responses to plasticity-inducing protocols. The ability to modulate GABA in a key core of the DMN by means of TBS may open new avenues to evaluate plasticity mechanisms in a key area for major neurodegenerative and psychiatric conditions.
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