Cortical stimulation in aphasia following ischemic stroke: toward modelguided electrical neuromodulation The aim of this paper is to integrate different bodies of research including brain traveling waves, brain neuromodulation, neural field modeling and poststroke language disorders in order to explore the opportunity of implementing modelguided, cortical neuromodulation for the treatment of poststroke aphasia. Worldwide according to WHO, strokes are the second leading cause of death and the third leading cause of disability. In ischemic stroke, there is not enough blood supply to provide enough oxygen and nutrients to parts of the brain, while in hemorrhagic stroke, there is bleeding within the enclosed cranial cavity. The present paper focuses on ischemic stroke. We first review accumulating observations of traveling waves occurring spontaneously or triggered by external stimuli in healthy subjects as well as in patients with brain disorders. We examine the putative functions of these waves and focus on poststroke aphasia observed when brain language networks become fragmented andor partly silent, thus perturbing the progression of traveling waves across perilesional areas. Secondly, we focus on a simplified model based on the current literature in the field and describe cortical traveling wave dynamics and their modulation. This model uses a biophysically realistic integrodifferential equation describing spatially distributed and synaptically coupled neural networks producing traveling wave solutions. The model is used to calculate wave parameters (speed, amplitude andor frequency) and to guide the reconstruction of the perturbed wave. A stimulation term is included in the model to restore wave propagation to a reasonably good level. Thirdly, we examine various issues related to the implementation modelguided neuromodulation in the treatment of poststroke aphasia given that closedloop invasive brain stimulation studies have recently produced encouraging results. Finally, we suggest that modulating traveling waves by acting selectively and dynamically across space and time to facilitate wave propagation is a promising therapeutic strategy especially at a time when a new generation of closedloop cortical stimulation systems is about to arrive on the market.

Cortical hemodynamic responses induced by lowintensity transcranial ultrasound stimulation of mouse cortex Abstract   Ultrasoundmediated neuromodulation is emerging as a key technology for targeted noninvasive brain stimulation, but key insights into its effects and doseresponse characteristics are still missing. The purpose of this study is to systematically evaluate the effect of lowintensity transcranial ultrasound stimulation (TUS) on complementary aspects of cerebral hemodynamic. We simultaneously record the EMG signal, local field potential (LFP) and cortical blood flow (CBF) using electrophysiological recording and laser speckle contrast imaging under ultrasound stimulation to simultaneously monitor motor responses, neural activities and hemodynamic changes during the application of lowintensity TUS in mouse motor cortex, using excitation pulses which caused whisker and tail movement. Our experimental results demonstrate interdependent TUSinduced motor, neural activity and hemodynamic responses that peak approximately 0.55s, 1.05s and 2.5s after TUS onset, respectively, and show a linear coupling relationship between their respective varying response amplitudes to repeated stimuli. We also found monotonic doseresponse parametric relations of the CBF peak value increase as a function of stimulation intensity and duration, while stimulus dutycycle had only a weak effect on peak responses. These findings demonstrate that TUS induces a change in cortical hemodynamics and LSCI provide a high temporal resolution view of these changes.