Burst-suppression is reactive to photic stimulation in comatose children with acquired brain injury  Dragos A. Nita, Mihai Moldovan, Roy Sharma, Sinziana Avramescu, Hiroshi Otsubo, Cecil D. Hahn  Clinical Neurophysiology  Volume 127, Issue 8, Pages 2921-2930 (August 2016) DOI: 10.1016/j.clinph.2016.03.029 Copyright © 2016 International Federation of Clinical Neurophysiology Terms and Conditions

Fig. 1 Quantification of binary BS pattern changes during photic stimulation. A “reactive” 60-s PS multichannel recording from patient four (P4) is presented in A. The rectified and standardized EEG (rEEG) is presented in gray. The corresponding measures of binary BS signals are indicated in black. The timing of photic stimuli (Phot) is marked with dots. Time origin is considered the onset of stimulation (seconds). The corresponding topographic map of the multichannel burst ratio (BR) distribution is presented below. The mean and SD maps of BR across all recordings is presented in B. Clinical Neurophysiology 2016 127, 2921-2930DOI: (10.1016/j.clinph.2016.03.029) Copyright © 2016 International Federation of Clinical Neurophysiology Terms and Conditions

Fig. 2 Quantification of binary BS pattern changes during photic stimulation. The multichannel EEG from patient four (P4) presented in Fig. 1 is reanalyzed by spatial averaging to compute the global field power (GFP). In panel A, the raw EEG is presented. The timing of photic stimuli is marked with vertical lines. Time origin is considered the onset of stimulation. The corresponding computed GFP is presented in panel B with the binary BS signal derived from thresholding at 75μV (details in text). The burst ratio (BR) is indicated. Clinical Neurophysiology 2016 127, 2921-2930DOI: (10.1016/j.clinph.2016.03.029) Copyright © 2016 International Federation of Clinical Neurophysiology Terms and Conditions

Fig. 3 Bursts evoked by photic stimulation. Panels A and B present 2 recordings form patient 3 (P3). Each panel depicts (from top to bottom): the global field power (GFP) during the whole session, a detailed GFP during stimulation (indicating the stimulus) and the bursts occurring within 1s after the stimuli (marked with an open symbol). The thick lines indicate the computed binary BS signal used to identify the burst onset. Both the burst ratio (BR) (in %) and the burst count (in bursts per minute – bpm) are presented. In panel C, the pooled delays between the burst and the preceding stimulus across all PS sessions (205 bursts) were used to construct a delay probability histogram. Clinical Neurophysiology 2016 127, 2921-2930DOI: (10.1016/j.clinph.2016.03.029) Copyright © 2016 International Federation of Clinical Neurophysiology Terms and Conditions

Fig. 4 Reactivity of BS to photic stimulation. In panel A, the burst ratio (BR) is presented as boxplot for the Pre, Stim and Post epochs respectively. The asterisk indicates a significant difference from Pre (Wilcoxon P<0.05). In panel B, the corresponding BR reactivity (measured as BRStim−BRPre) is plotted against BRPre. The regression line is indicated (slope −0.19; Y-intercept 16.44). The stippled line indicates the maximum theoretical reactivity, for a specific BRPre, In panel C, the group burst counts are presented as boxplots for the Pre, Stim and Post epochs. The asterisk indicates a significant difference from Pre (Wilcoxon P<0.05). Panel D presents the relationship between the BR reactivity and the increase in burst count. The regression line is indicated (slope 0.23; Y-intercept 1.29). Numerical labels indicate the patient from whom the epochs came. Clinical Neurophysiology 2016 127, 2921-2930DOI: (10.1016/j.clinph.2016.03.029) Copyright © 2016 International Federation of Clinical Neurophysiology Terms and Conditions

Fig. 5 Heart rate reactivity during photic stimulation. Panel A presents recordings from patient 3 (P3) above and patient 1 (P1) below. Each recording presents (from top to bottom): the global field power, EGC, and heart rate (HR). The computed binary BS signal used to identify the burst onset is indicated, together with the burst-suppression ratio (in%) and the burst count (in burst per minute – bpm). In panels B, C and D boxplots for the Pre, Stim and Post epochs are presented for the group heart rates, SDNN and pNN5 respectively. Asterisks indicate significant difference from Pre (Wilcoxon P<0.05). Panel E presents the relationship between the BR reactivity and the decrease in pNN5. Numerical labels indicate the patient from whom the epochs came. Clinical Neurophysiology 2016 127, 2921-2930DOI: (10.1016/j.clinph.2016.03.029) Copyright © 2016 International Federation of Clinical Neurophysiology Terms and Conditions

Fig. 6 Standardized reactivity of BR to photic stimulation. The standardized reactivity measure was calculated as the adimensional slope of the linear regression of reactivity versus BRPre constrained so that reactivity is 0 at a BRPre of 88%. An example measurement for P4 is illustrated in A (slope −0.48; Y-intercept 42.62). The absolute slope of 0.48 reflects the standardized reactivity for that patient. The relationship between standardized reactivity and the GCS score (Table 1) across all subjects is presented in B. The regression line is indicated (slope 15.08; Y-intercept 6.51). Clinical Neurophysiology 2016 127, 2921-2930DOI: (10.1016/j.clinph.2016.03.029) Copyright © 2016 International Federation of Clinical Neurophysiology Terms and Conditions