Analysis of sympathetic responses to cognitive stress and pain through skin sympathetic nerve activity and electrodermal activity

We explored the non-invasive evaluation of the sympathetic nervous system (SNS) by employing two distinct physiological signals: skin sympathetic nerve activity (SKNA), extracted from electrocardiogram (ECG) signals, and electrodermal activity (EDA), a well-studied marker in the context of the SNS assessment. Our investigation focused on cognitive stress and pain; two conditions closely associated with the SNS. We sought to determine if the information and dynamics of EDA could be derived from the novel SKNA signal. To this end, ECG and EDA signals were recorded simultaneously during three experiments aimed at sympathetic stimulation, Valsalva maneuver (VM), Stroop test, and thermal-grill pain test. We calculated the integral area under the rectified SKNA signal (iSKNA) and decomposed the EDA signal to its phasic component (EDAphasic). An average delay of more than 4.6 s was observed in the onset of EDAphasic bursts compared to their corresponding iSKNA bursts. After shifting the EDAphasic segments by the extent of this delay and smoothing the corresponding iSKNA bursts, our results revealed a strong average correlation coefficient of 0.85±0.14 between the iSKNA and EDAphasic bursts, indicating a noteworthy similarity between the two signals. We also reconstructed the EDA signals with time-varying sympathetic (TVSymp) and modified TVSymp (MTVSymp) methods. Then we extracted the following features from iSKNA, EDAphasic, TVSymp, and MTVSymp signals: peak amplitude, average amplitude (aSKNA), standard deviation (vSKNA), and the cumulative duration during which the signals had higher amplitudes than a specified threshold (HaSKNA). A strong average correlation of 0.89±0.18 was found between vSKNA and subjects' self-rated pain levels during the pain test. Our statistical analysis also included applying Linear Mixed-Effects Models to check if there were significant differences in features across baseline and different levels of SNS stimulation. We then assessed the discriminating power of the features using Area Under the Receiver Operating Characteristic Curve (AUROC) and Fisher's Ratio. Finally, using all the four EDA features, a multi-layer perceptron (MLP) classifier reached the classification accuracies 95.56%, 89.29%, and 67.88% for the VM, Stroop, and thermal-grill pain control and stimulation classes. On the other hand, the highest classification accuracies based on SKNA features were achieved using K-nearest neighbors (KNN) (98.89%), KNN (89.29%), and MLP (95.11%) classifiers for the same experiments. Our comparative analysis showed the feasibility of SKNA as a novel tool for assessing the SNS with accurate classification capability, with a faster onset of amplitude increase in response to SNS activity, compared to EDA.