Low-frequency oscillations in the brain show differential regional associations with severity of cerebral small vessel disease: a systematic review

• Published in: Frontiers in neuroscience 2023-08, Vol.17, p.1254209-1254209
• Main Authors: Thomas, James, Jezzard, Peter, Webb, Alastair J. S.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Brain; Brain mapping; cerebral small vessel disease; Cortex (temporal); Cross-sectional studies; Data acquisition; endothelial dysfunction; fMRI; Functional magnetic resonance imaging; low-frequency oscillations; Magnetic resonance imaging; Meta-analysis; Neuroimaging; neuroimaging markers; Neuroscience; Oscillations; Physiology; Substantia alba; Systematic review; Vascular diseases
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2023.1254209

Background: Cerebral small vessel disease (cSVD) is associated with endothelial dysfunction but the pathophysiology is poorly understood. Low-frequency oscillations (LFOs) in the BOLD signal partly reflect cerebrovascular function and have the potential to identify endothelial dysfunction in cSVD. A systematic review was performed to assess the reported relationships between imaging markers of cSVD and LFOs. Methods: Medline and EMBASE were searched for original studies reporting an association between LFOs and STRIVE-defined imaging markers of cSVD, including: white matter hyperintensities (WMH), enlarged perivascular spaces, lacunes, CADASIL, and cerebral microbleeds, from inception to September 1, 2022. Variations in LFOs were extracted, where available, on a global, tissue-specific, or regional level, in addition to participant demographics, data acquisition, methods of analysis, and study quality. Where a formal meta-analysis was not possible, differences in the number of studies reporting LFO magnitude by presence or severity of cSVD were determined by sign test. Results: 15 studies were included from 841 titles. Studies varied in quality, acquisition parameters, and in method of analysis. Amplitude of low-frequency fluctuation (ALFF) in resting state fMRI was most commonly assessed (12 studies). Across 15 studies with differing markers of cSVD (9 with WMH; 1 with cerebral microbleeds; 1 with lacunar infarcts; 1 with CADASIL; 3 with multiple markers), LFOs in patients with cSVD were decreased in the posterior cortex (22 of 32 occurrences across all studies, p=0.05), increased in the deep grey nuclei (7 of 7 occurrences across all studies, p=0.016), and potentially increased in the temporal lobes (9 of 11 occurrences across all studies, p=0.065). Conclusions: Despite limited consensus on the optimal acquisition and analysis methods, there was reasonably consistent regional variation in LFO magnitude by severity of cSVD markers, supporting its potential as a novel index of endothelial dysfunction. We propose a consistent approach to measuring LFOs to characterise targetable mechanisms underlying cSVD.