RT Journal Article SR Electronic T1 Greater TMS-evoked frontoparietal effective connectivity is correlated with better cognitive performance JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.03.234518 DO 10.1101/2020.08.03.234518 A1 Morris, Timothy P. A1 Redondo-Camos, Maria A1 Cattaneo, Gabriele A1 Macia, Didac A1 Solana-Sanchez, Javier A1 Espanya-Irla, Goretti A1 Delgado-Gallén, Selma A1 Alviarez-Schulze, Vanessa A1 Pachón-Garcia, Catherine A1 Santarnecchi, Emiliano A1 Tadayon, Ehsan A1 Ozdemir, Recep A1 Muñoz, Jose Ma Tormos A1 Batres-Faz, David A1 Pascual-Leone, Alvaro A1 Shafi, Mouhsin M. YR 2020 UL http://biorxiv.org/content/early/2020/08/04/2020.08.03.234518.abstract AB Fronto-parietal activity has been related to fluid intelligence and flexible cognitive control. However, causal insights on this relation are lacking. We used real-time integration of MRI-guided TMS and EEG to characterize the spatial and temporal properties of signal propagation between these two regions and relate them to cognitive performance.31 healthy adults (55 ±6 years, 20 female) underwent TMS-EEG and a full cognitive assessment. Local and propagated current from 5 source space-reconstructed scouts ipsilateral to two stimulation sites (pre frontal cortex (PFC) and inferior parietal lobule (IPL)) was quantified in two-time windows (15-40ms and 40-80ms) and related to domain-general (global cognition) and domain-specific (memory, working memory, reasoning, flexibility, lexical access and visuo-spatial) cognitive functions.TMS-evoked activity from stimulation of the PFC and the IPL resulted in local and distributed activity across frontoparietal regions. TMS-evoked activity in local regions was not correlated with cognitive functions. In response to TMS of the PFC, propagated current to the distal superior parietal scout in the first 15-40ms was significantly associated with global cognition (β = 2.63, SE = .898, p = .008, R2 = .31). Similarly, following TMS of the IPL, propagation to the middle prefrontal gyrus scout (15-40ms) was significantly associated with global cognition (β = 2.67, SE = 1.289, p = .025, R2 = .27). In an exploratory step, domain-specific correlations were seen in the PFC condition.Locally evoked activity measured via source space reconstruction from TMS of two association hubs is not associated with cognitive functions. However, the propagation of the TMS pulse through frontoparietal connections is associated with overall cognitive ability. These associations are driven by a number of cognitive domains in the PFC stimulation condition.Competing Interest StatementDr. A. Pascual-Leone serves on the scientific advisory boards for Starlab Neuroscience, Neuroelectrics, Magstim, Magventure, and Nexstim; is co-founder of Linus Health; and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging. All other authors disclose no conflicts of interest including no financial, personal, or other relationships with other people or organizations that could inappropriately influence this work