From Silence to Awakening: The Role of Amplitude of Low-Frequency Fluctuations in Predicting Recovery After Spinal...

Disorders of consciousness (DoCs) following traumatic brain injury (TBI), or cerebrovascular disease (CVD) are difficult to prognose, as reliable biomarkers are lacking. Resting-state functional magnetic resonance imaging (fMRI) amplitude of low-frequency amplitude (ALFF) may capture etiology-specific neural activity, but its prognostic value for spinal cord stimulation (SCS) outcomes remains unknown. In this study we therefore investigated etiology-specific ALFF patterns in TBI- and CVD-induced DoCs and evaluated their prognostic value for recovery after SCS.

Resting-state fMRI data from patients with TBI (n = 16) and CVD (n = 15), and healthy controls (n = 12), were analyzed. Whole-brain ALFF differences were also compared between the groups. Correlations between ALFF and 6-month post-SCS Coma Recovery Scale-Revised (CRS-R) score improvements were assessed. Logistic regression was used to identify consciousness recovery markers.

Compared with healthy controls, patients with TBI demonstrated a significant increase in ALFF within the bilateral insula, thalamus, and brainstem (p < 0.05), suggesting compensatory neural hyperactivity potentially involving glutamatergic pathways. Patients with CVD exhibited elevated ALFF in the contralateral sensorimotor cortex (p < 0.05), indicating ipsilateral neural reorganization. Notably, the thalamic ALFF were strongly correlated with consciousness recovery, as measured by improvements in CRS-R score at 6 months in both the TBI (r= 0.64, p = 0.0071) and CVD (r = 0.59, p = 0.02) groups. Furthermore, logistic regression analysis identified increased ALFF in the anterior cingulate cortex-thalamic loop (odds ratio [OR] = 3.21, p < 0.05) as a potential cross-etiology biomarker for recovery following SCS.

ALFF reveal distinct neuroplasticity mechanisms, including compensatory activation in TBI and ipsilateral reorganization in CVD. Elevated anterior cingulate cortex (ACC)-thalamic ALFF are a key cross-etiology biomarker for consciousness recovery to guide SCS target selection.