Hemodynamic correlates of fluctuations in neuronal excitability: A simultaneous Paired Associative Stimulation (PAS) and functional near infra-red spectroscopy (fNIRS) study

Background The relationship between task-related hemodynamic activity and brain excitability is poorly understood in humans as it is technically challenging to combine simultaneously non-invasive brain stimulation and neuroimaging modalities. Cortical excitability corresponds to the readiness to become active and as such it may be linked to metabolic demand. Hypotheses Cortical excitability and hemodynamic activity are positively linked so that increases in hemodynamic activity correspond to increases in excitability and vice-versa. Methods Fluctuations of excitability and hemodynamic activity were investigated via simultaneous Transcranial Magnetic Stimulation (TMS) and functional Near Infrared Spectroscopy (fNIRS). Sixteen healthy subjects participated in a sham-controlled, pseudorandomized, counterbalanced study with PAS (PAS10/PAS25/Sham) on the right primary motor cortex (M1). The relationship between M1 excitability (Motor Evoked Potentials, MEP) and hemodynamic responses to finger tapping reconstructed via personalized fNIRS was assessed. Results Hemodynamic activity exhibited a significant correlation with cortical excitability: increased HbO and HbR (absolute amplitude) corresponded to increased excitability and vice-versa (r=0.25; p=0.03 and r=0.16; p=0.17, respectively). The effect of PAS on excitability and hemodynamic activity showed a trend of positive correlation: correlation of MEP ratios (post-PAS/pre-PAS) with HbO and HbR ratios (r=0.19, p=0.29; r=0.18, p=0.30, respectively). Conclusions TMS-fNIRS is a suitable technique for simultaneous investigation of excitability and hemodynamic responses and indicates a relationship between these two cortical properties. PAS effect is not limited to cortical excitability but also impacts hemodynamic processes. These findings have an impact on the application of neuromodulatory interventions in patients with neuropsychiatric disorders. ### Competing Interest Statement The authors have declared no competing interest.