The Cerebrovascular Reactivity Adjusted Fractional Amplitude of Low-Frequency Fluctuations Abnormalities in Middle Cerebral Artery Stenosis and Occlusive Disease

Translational Stroke Research (2026) 17:38 https://doi.org/10.1007/s12975-026-01430-z RESEARCH The Cerebrovascular Reactivity Adjusted Fractional Amplitude of Low-Frequency Fluctuations Abnormalities in Middle Cerebral Artery Stenosis and Occlusive Disease Liqing Zhang1 · Luoyu Wang2,3 · Xue Tang4 · Yidi Zhu4 · Rong Wang1 · Zhongxiang Ding1 Received: 7 October 2025 / Revised: 14 March 2026 / Accepted: 24 March 2026 / Published online: 1 April 2026 © The Author(s) 2026 Abstract This study investigated the variation characteristics of static fractional amplitude of low-frequency fluctuations (sfALFF) and dynamic fALFF (dfALFF) in Middle cerebral artery stenosis or occlusion(MCA-S) patients, and explored these two indicators alterations with cerebrovascular reactivity (CVR) correction. A total of 41 MCA-S patients and 50 matched controls underwent resting-state functional MRI and neuropsychological testing. Group differences in sfALFF/dfALFF were compared between the two groups, and the brain regions with differences in sfALFF/dfALFF with and without CVR correction were explored. Subsequently, partial correlation analysis was employed to evaluate the correlation between the abnormal brain regions and neuropsychological assessments. After CVR correction, MCA-S patients displayed increased sfALFF in Vermis_6, ipsilesional Cerebelum_8, Hippocampus, and other regions, alongside elevated dfALFF in Vermis_7, ipsilesional Hippocampus, and contralesional Cerebelum_8 (P < 0.001). No significant correlations were found between fALFF metrics and neuropsychological scores post-Bonferroni correction. Uncorrected analyses showed group differences in sfALFF/CVR within ipsilesional Occipital_Mid and Parietal_Inf, while CVR-adjusted results revealed changes in ipsilesional Cerebelum_8 and contralesional Caudate (P < 0.05). For dfALFF, uncorrected differences emerged in ipsilesional Postcentral, whereas CVR correction highlighted ipsilesional Temporal_Inf alterations. In summary, MCA-S patients exhibited abnormal neuronal activity associated with both sfALFF and dfALFF. With CVR correction, vascular confounding effects on the BOLD signal were partially mitigated, thereby enabling more accurate reflection of underlying neural activity alterations. Keywords Resting-state functional magnetic resonance imaging · Fractional amplitude of low-frequency fluctuations · Cerebrovascular reactivity · Middle cerebral artery · Stenosis Liqing Zhang and Luoyu Wang contributed equally to this work and share first authorship. Communicated by: Huimahn Choi 1 Luoyu Wang 2 School of Biomedical Engineering, ShanghaiTech University, Shanghai 201210, China Zhongxiang Ding 3 Center for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 311121, China 4 School of Medical Imaging, Hangzhou Medical College, Hangzhou 310006, China Department of Radiology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, China 13 38 Page 2 of 15 Introduction Middle cerebral artery stenosis or occlusion(MCA-S) is a primary cause of ischemic stroke(IS) worldwide, and constitutes the most common type and an independent risk factor for stroke in Asian populations [1, 2]. The middle cerebral artery is frequently implicated in IS, often serving as the critical vessel involved in the condition’s pathogenesis. MCA-S induces significant hemodynamic disturbances [3], such as reduced cerebral blood flow (CBF) and a compromised oxygen extraction fraction, which ultimately precipitate ischemic brain injury and stroke. Chronic cerebral hypoperfusion due to intracranial arterial stenosis or occlusion is a key mechanism leading to vascular cognitive impairment and dementia [4, 5]. Moderate or severe vascular stenosis has been specifically linked to cognitive impairment, which can adversely affect patients’ daily life and behavior [6]. Given its high morbidity and association with poor neurological outcomes, elucidating the cerebral pathophysiology of MCA-S is essential for developing effective diagnostic and therapeutic strategies. Resting-state functional magnetic resonance imaging (rsfMRI) is a powerful tool for investigating brain activity in vivo, providing insights into the organization and dynamics of brain networks under normal and pathological conditions. A prominent analytical method in this field is the fractional Amplitude of Low-Frequency Fluctuation (fALFF) [7], which quantifies the relative amplitude of low-frequency fluctuations (0.01–0.08 Hz) in the blood oxygen leveldependent (BOLD) signal. Specifically, fALFF is calculated as the ratio of the power within this low-frequency band to the power across the entire detectable frequency spectrum of the Fourier-transformed time series. This normalization mitigates the influence of high-frequency physiological noise, such as respiratory and cardiac. Consequently, fALFF has become a widely utilized biomarker in neuropsychiatric research for conditions including stroke [8], depression [9], and Alzheimer’s disease [10](AD). Although fALFF provides valuable information regarding the static characteristics of brain activity, it cannot reflect the dynamic, time-varying nature of neural processes. The brain is a highly adaptive and dynamic system that continuously adjusting its activity in response to internal and external stimuli [11, 12]. To better characterize these temporal fluctuations, the dynamic fractional amplitude of lowfrequency fluctuations (dfALFF) was developed. dfALFF reflects the temporal variability in the fALFF values across different brain regions, offering further insight into how neural activity fluctuates over time [13, 14]. Combining this dynamic analysis with the static fALFF (sfALFF) provides a more comprehensive characterization of brain activity, elucidating both the spatial and temporal aspects of neural 13 Translational Stroke Research (2026) 17:38 processes. However, the application of sfALFF and dfALFF in diseases involving intracranial vascular stenosis, such as MCA-S, remains unexplored. However, calculating fALFF from BOLD signals may be confounded by hemodynamic influences. In fact, BOLD signals in fMRI do not directly measure neuronal activity but instead reflect hemodynamic changes mediated by neurovascular coupling, a process through which neuronal activation induces vascular responses to meet metabolic demands [15]. Consequently, the BOLD signal is modulated by both neural activity and vascular physiology, complicating the interpretation of fMRI data [16, 17]. Recent study have underscored the critical role of cerebrovascular reactivity (CVR)—the capacity of blood vessels to dilate in response to neuronal activation—in modulating BOLD signals [15]. CVR is a key determinant of the brain’s capacity to sustain sufficient blood flow during increased neural activity, and its impairment can affect the BOLD signal. Golestani et al. [18] showed a (...truncated)