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

James Thomas; Peter Jezzard; Alastair J S Webb

doi:10.3389/fnins.2023.1254209

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

Front Neurosci. 2023 Aug 31:17:1254209. doi: 10.3389/fnins.2023.1254209. eCollection 2023.

Authors

James Thomas¹, Peter Jezzard², Alastair J S Webb¹

Affiliations

¹ Nuffield Department of Clinical Neurosciences, Wolfson Centre for Prevention of Stroke and Dementia, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
² FMRIB Division, Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.

Abstract

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).

Conclusion: 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.

Keywords: cerebral small vessel disease; endothelial dysfunction; fMRI; low-frequency oscillations; neuroimaging markers.

Publication types

Review