Hurst Exponent (HE) is a scalar measurement of long-term temporal memory of a time series. The HE has been found in previous studies to be an effective means of measuring the long-range temporal dependence of brain activity as measured by fMRI. We hypothesize that the HE can be associated with impairment in Multiple Sclerosis (MS), therefore can be an imaging biomarker of MS.
The primary goal of the study is to assess how well HE measurements can distinguish MS patients from healthy controls (HC), as well as MS patients with impairment from those without impairment. The second objective was to identify which brain regions’ HE alterations are associated with impairment in MS.
Fifteen HC (age: 43.66±8.64, 53% female) and 76 MS patients (age:45.28±11.46 years, 65% female, disease duration:12.29±7.25 years) were included in our study; 23 had EDSS2 at study baseline. Logistic ridge regression (LR) was used to classify two groups: (1) HC vs MS patients and (2) MS patients with vs without impairment. The classification tasks were performed using HE measurements in 86 cortical and subcortical regions. Five-fold cross-validation was used to train, validate, and test the model, with 10 outer loop repetitions. Area Under ROC curve (AUC) over the folds was used to assess classification performance.
HE was found to be significantly higher in the non-impaired group compared to the impaired group in the right superior frontal gyrus (corrected p-value=0.025). The classification of HC vs MS had an AUC of 0.65 (IQR:0.18), while the task of classifying MS patients by impairment level had an AUC of 0.63 (IQR: 0.12). For the classification of HC vs MS, the regions that were the most predictive were in deep gray matter. Lower HE in the left amygdala, left thalamus and left putamen, and higher HE in the left hippocampus was associated with MS. For the classification of impairment level in MS, deep gray matter regions were also important, as were HE in the frontal lobe. Lower HE in the left caudate, right and left amygdala, and left superior frontal and higher HE in the right ventral DC were associated with more impairment in MS.
HE was found to be moderately discriminative between HC and MS and within impairment levels in MS. HE in subcortical and superior frontal regions were found to be important biomarkers of impairment severity in MS, as well as in distinguishing MS patients from HC. Further research is necessary to identify the mechanism driving these differences.