P227 TMS-induced modulation of Default-Mode Network regional neurochemistry relates to functional connectivity, brain structure and cognition in healthy aging

Abstract

The Default-Mode Network (DMN) is compromised in healthy aging and in several neurodegenerative diseases. Glutamate and GABA are the main excitatory and inhibitory human neurotransmitters respectively, and are highly implicated in neuroplasticity and brain activation, where N-acetyl-aspartate (NAA) seems also to be involved. The aim of the present investigation was to determine if metabolite concentrations of these neurochemicals can be modulated in core regions of the DMN in healthy elderly. For this purpose we used a plasticity inducing TMS protocol, intermittent theta-burst stimulation (iTBS). Twenty-one cognitively healthy elderly (mean age: 67.29, SD: 4.88) were included. Individually-guided neuronavigated iTBS was applied over the left inferior parietal lobe (IPL) in the middle of two Magnetic Resonance Spectroscopy (MRS) acquisitions measuring GABA, Glx (Glutamate + Glutamine) and total NAA (tNAA) concentrations. The MRS voxel was centered over the parietal cingulate cortex (PCC). Subjects were randomly assigned to receive real (N = 11) or sham (N = 10) iTBS. A resting-state functional Magnetic Resonance Imaging (rs-fMRI) acquisition and a high-resolution 3D sequence were also acquired. TNAA decreased significantly within the PCC after iTBS application (F = 5.271, p = 0.035; Fig. 1). Greater neurochemical response to iTBS in posteromedial areas was related to (1) lower baseline rs-fMRI connectivity between the stimulated area and the PCC region (r = −0.649, p = 0.031; Stim-to-PCC in Fig. 2), (2) reduced brain atrophy in different cortical regions (i.e. paracentral lobe: r = 0.751, p = 0.008), and (3) better scores in a phonetic fluency task (r = 0.663, p = 0.026). Our findings show that a TMS intervention is able to modulate tNAA concentrations from the stimulation site to a distal DMN core area. Further, the magnitude of the observed neurochemical modulation was related to baseline connectivity between these two areas, as with greater structural brain integrity and better cognitive performance. Demonstration of experimentally-controlled neurochemical modulation in key cortical areas opens the possibility of TMS to be used as a tool to interrogate brain neurochemical changes in aging and in early neurodegenerative conditions. Download : Download high-res image (152KB) Download : Download full-size image Download : Download high-res image (230KB) Download : Download full-size image