Exploration of simultaneous transients between cerebral hemodynamics and the autonomic nervous system using windowed time-lagged cross-correlation matrices: a CENTER-TBI study
Authors: Uryga Agnieszka , Mataczyński Cyprian , Pelah Adam I. , Burzyńska Małgorzata , Robba Chiara , Czosnyka Marek ,   CENTER-TBI high-resolution sub-study participants and investigators, Anke Audny , Beer Ronny , Bellander Bo-Michael , Beqiri Erta , Buki Andras , Cabeleira Manuel , Carbonara Marco , Chieregato Arturo , Citerio Giuseppe , Clusmann Hans , Czeiter Endre , Depreitere Bart , Ercole Ari , Frisvold Shirin , Helbok Raimund , Jankowski Stefan , Kondziella Daniel , Koskinen Lars-Owe , Kowark Ana , Menon David K. , Meyfroidt Geert , Moeller Kirsten , Nelson David , Piippo-Karjalainen Anna , Radoi Andreea , Ragauskas Arminas , Raj Rahul , Rhodes Jonathan , Rocka Saulius , Rossaint Rolf , Sahuquillo Juan , Sakowitz Oliver , Smielewski Peter , Stocchetti Nino , Sundstrom Nina , Takala Riikka , Tamosuitis Tomas , Tenovuo Olli , Unterberg Andreas , Vajkoczy Peter , Vargiolu Alessia , Vilcinis Rimantas , Wolf Stefan , Younsi Alexander , Zeiler Frederick A. 
Published: December 2024

Abstract

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.