AbstractWe introduce theoretical concepts based on chaos control to stabilize in acute stroke the tissue at risk of progressive damage by preventing adverse effects of waves of mass neuronal depolarization. Moreover, we present clinical electrocorticography (ECoG) recordings of relevant signals suggested for the feedback control. The recordings are performed in combination with novel subdural opto-electrode technology for simultaneous laser-Doppler flowmetry in patients with aneurysmal subarachnoid haemorrhage (aSAH). In aSAH patients waves of spreading depolarization (SD) have a high incidence and cause hypoxia in tissue at risk, and, importantly, the haemodynamic response is the inverse of that seen in healthy tissue. In previous clinical studies, clusters of prolonged SDs have been measured in aSAH patients in close proximity to structural brain damage as assessed by neuroimaging, and, in theoretical studies, a mechanism was presented, suggesting how a failure of internal feedback could be a putative mechanism of such SD cluster patterns in acute stroke. This failing internal feedback control is now suggested to be replaced by ECoG-based short-range recurrent functional stimulation that initiates the normal hyperperfusion haemodynamic response in a demand-controlled way and stabilizes the tissue at risk during the critical phase of SD passage. The suggested method has three key features: (i) it is short-range, i.e., in the order of the distance of the ECoG electrode strip, (ii) it is demand-controlled, and (iii) it uses no prior knowledge of the target state, in particular, it adapts to conditions in the healthy physiological range. On-demand type stimulation provides minimal invasive feedback as the control force is off when the target state is reached, i.e., the tissue at risk is without SD or it is back to the physiological range (out of risk). These last two features (ii-iii) are shared with classical methods of chaos control, where major progress was made in the last years with respect to extensions for spatio-temporal wave patterns. A detailed bifurcation analysis of the nonlinear model is presented, in particular, the SD cluster forming cortical state is suggested to be caused by a delay-induced saddle-node bifurcation.