Neurochemical Modulation in Posteromedial Default-mode Network Cortex Induced by Transcranial Magnetic Stimulation

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.