Exploration of simultaneous transients between cerebral hemodynamics and the autonomic nervous system using windowed time-lagged cross-correlation matrices: a CENTER-TBI study

Background: Traumatic brain injury (TBI) can significantly disrupt autonomic nervous system (ANS) regulation, increasing the risk for secondary complications, hemodynamic instability, and adverse outcome. This retrospective study evaluated windowed time-lagged cross-correlation (WTLCC) matrices for describing cerebral hemodynamics–ANS interactions to predict outcome, enabling identifying high-risk patients who may benefit from enhanced monitoring to prevent complications. Methods: The first experiment aimed to predict short-term outcome using WTLCC-based convolution neural network models on the Wroclaw University Hospital (WUH) database (Ptraining = 31 with 1,079 matrices, Pval = 16 with 573 matrices). The second experiment predicted long-term outcome, training on the CENTER-TBI database (Ptraining = 100 with 17,062 matrices) and validating on WUH (Pval = 47 with 6,220 matrices). Cerebral hemodynamics was characterized using intracranial pressure (ICP), cerebral perfusion pressure (CPP), pressure reactivity index (PRx), while ANS metrics included low-to-high-frequency heart rate variability (LF/HF) and baroreflex sensitivity (BRS) over 72 h. Short-term outcome at WUH was assessed using the Glasgow Outcome Scale (GOS) at discharge. Long-term outcome was evaluated at 3 months at WUH and 6 months at CENTER-TBI using GOS and GOS-Extended, respectively. The XGBoost model was used to compare performance of WTLCC-based model and averaged neuromonitoring parameters, adjusted for age, Glasgow Coma Scale, major extracranial injury, and pupil reactivity in outcome prediction. Results: For short-term outcome prediction, the best-performing WTLCC-based model used ICP-LF/HF matrices. It had an area under the curve (AUC) of 0.80, vs. 0.71 for averages of ANS and cerebral hemodynamics metrics, adjusted for clinical metadata. For long-term outcome prediction, the best-score WTLCC-based model used ICP-LF/HF matrices. It had an AUC of 0.63, vs. 0.66 for adjusted neuromonitoring parameters. Conclusions: Among all neuromonitoring parameters, ICP and LF/HF signals were the most effective in generating the WTLCC matrices. WTLCC-based model outperformed adjusted neuromonitoring parameters in short-term but had moderate utility in long-term outcome prediction.