P 132. Modulation of encoding-related networks by intermittent TBS stimulation in healthy aging

Abstract

Question Memory dysfunction is one of the main cognitive hallmarks of aging. Repetitive Transcranial Magnetic Stimulation induces brain plasticity changes that may underlie its capacity to modulate associative memory in elders (Sole-Padulles et al., 2006). Memory recall also depends on the manner in which stimuli are encoded (Innocenti et al., 2010) (i.e. the depth or shallowness of the processing) according to level of processing (LOP) theory (Craik and Lockhart, 1972). Our aim was to investigate the impact of a single session of excitatory intermittent theta burst stimulation (iTBS) on behavioral outcomes and the expression of brain networks in healthy elders, related to an episodic memory task with two types of processing. Materials and methods After an initial MRI scanner and neuropsychological testing 21 healthy elder subjects (71.6yo.) were randomly assigned to Real ( n =11) or Sham iTBS group. Subjects underwent a baseline functional MRI session (Siemens 3T) followed by Real or Sham iTBS (MagVenture, MagPro x100 Opt; 80% AMT; 600pulses). iTBS was neuronavigated (Nexstim-NBS-eXimia) over the Left Inferior Frontal Gyrus (LIFG) (group coordinates from metanalysis (Kim, 2011)). Immediately after iTBS, subjects realized a second equivalent MRI session. The memory task consisted in 8 24″ block-design paradigm were subjects were instructed to try to remember words either using deep (i.e. semantic) or shallow (i.e. perceptual) encoding. Repeated stimuli were also presented for control purposes. After both MRI sessions participants performed a recognition memory test. Results In a three way ANOVA, only main effects of LOP ( p For fMRI results, we found a significant interaction in Encoding Deep>Repeated Deep in Left and Right occipital cortex and in Encoding Deep>Encoding Shallow contrast in the anterior LIFG (Fig. 1) and in Left visual cortex indicating that Real iTBS compared to Sham stimulation resulted in increased BOLD signal but only associated to deep encoding processes (positive slope differences). Furthermore, these areas corresponded to those related to deep memory encoding in our baseline analyses. Conclusion While failing to observe a behavioral effect, iTBS specifically modulated the expression of a brain network only when subjects engaged a cognitive process related to encoding at Deeper LOP. Within the general framework of the state-dependency postulates (Silvanto et al., 2008), we suggest that our results provide further first evidence, in a study combining neuroimaging and a behavioral paradigm in elder participants, of the importance of considering the interaction between the objective brain stimulation parameters with the functional state of the neuronal populations, to account for the brain responses to non-invasive brain stimulation studies in cognitive studies in aging population.