Abstract
BackgroundNeuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood. Serum NfL has recently emerged as a promising biomarker for grading axonal damage, monitoring treatment responses, and prognosis in neurological diseases. Importantly, serum NfL levels also increase with aging, and the interpretation of serum NfL levels in neurological diseases is incomplete due to lack of a reliable model for age-related variation in serum NfL levels in healthy subjects.MethodsGraph signal processing (GSP) provides analytical tools, such as graph Fourier transform (GFT), to produce measures from functional dynamics of brain activity constrained by white matter anatomy. Here, we leveraged a set of features using GFT that quantified the coupling between blood oxygen level dependent signals and structural connectome to investigate their associations with serum NfL levels collected from healthy subjects and former athletes with history of concussions.ResultsHere we show that GSP feature from isthmus cingulate in the right hemisphere (r-iCg) is strongly linked with serum NfL in healthy controls. In contrast, GSP features from temporal lobe and lingual areas in the left hemisphere and posterior cingulate in the right hemisphere are the most associated with serum NfL in former athletes. Additional analysis reveals that the GSP feature from r-iCg is associated with behavioral and structural measures that predict aggressive behavior in healthy controls and former athletes.ConclusionsOur results suggest that GSP-derived brain features may be included in models of baseline variance when evaluating NfL as a biomarker of neurological diseases and studying their impact on personality traits.
Highlights
Neuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood
Our results for univariate feature analysis and PLSR analysis show that a distinct set of Graph signal processing (GSP) features are statistically relevant for serum NfL in healthy controls (HC) and ExPro cohorts (Fig. 2)
We observed that the set of GSP features associated with serum NfL were dominated by high graph frequency features (18 out of 24 with uncorrected p-value < 0.05, see Fig. 2c), in the temporal lobe, lingual and parahippocampus areas in the left hemisphere, and entorhinal in the right hemisphere (Fig. 2f)
Summary
We aimed to explore the statistical correspondence of GSP features in the context of serum NfL levels in the two cohorts under both statistical paradigms
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