Background Neurological symptoms associated with coronavirus disease 2019 (COVID‐19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post‐COVID‐19 timeframe. Purpose To determine whether adults who experienced flu‐like symptoms due to COVID‐19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu‐like symptoms but tested negative for COVID‐19. Study Type Prospective observational. Population A total of 39 adults who previously self‐isolated at home due to COVID‐19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu‐like symptoms but had a negative COVID‐19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). Field Strength and Sequences A 3.0 T; T1 ‐weighted magnetization‐prepared rapid gradient and echo‐planar turbo gradient‐spin echo arterial spin labeling sequences. Assessment Arterial spin labeling was used to estimate CBF. A self‐reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID‐19 and control groups and between those with ( n = 11) and without self‐reported ongoing fatigue ( n = 28) within the COVID‐19 group. Statistical Tests Between‐group and within‐group comparisons of CBF were performed in a voxel‐wise manner, controlling for age and sex, at a family‐wise error rate of 0.05. Results Relative to controls, the COVID‐19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t ‐statistic = 5.21). Within the COVID‐19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self‐reported on‐going fatigue. Data Conclusion These cross‐sectional data revealed regional CBF decreases in the COVID‐19 group, suggesting the relevance of brain physiology in the post‐COVID‐19 timeframe. This research may help elucidate the heterogeneous symptoms of the post‐COVID‐19 condition. Evidence Level 2. Technical Efficacy Stage 3.
There remain few efficacious treatments for bipolar depression, which dominates the course of bipolar disorder (BD). Despite multiple studies reporting associations between depression and cerebral blood flow (CBF), little is known regarding CBF as a treatment target, or predictor and/or indicator of treatment response, in BD. Nitrous oxide, an anesthetic gas with vasoactive and putative antidepressant properties, has a long history as a neuroimaging probe. We undertook an experimental medicine paradigm, coupling in-scanner single-session nitrous oxide treatment of bipolar depression with repeated measures of CBF.In this double-blind randomized controlled trial, 25 adults with BD I/II and current treatment-refractory depression received either: (1) nitrous oxide (20 min at 25% concentration) plus intravenous saline (n = 12), or (2) medical air plus intravenous midazolam (2 mg total; n = 13). Study outcomes included changes in depression severity (Montgomery-Asberg Depression Rating Scale scores, primary) and changes in CBF (via arterial spin labeling magnetic resonance imaging).There were no significant between-group differences in 24-h post-treatment MADRS change or treatment response. However, the nitrous oxide group had significantly greater same-day reductions in depression severity. Lower baseline regional CBF predicted greater 24-h post-treatment MADRS reductions with nitrous oxide but not midazolam. In region-of-interest and voxel-wise analyses, there was a pattern of regional CBF reductions following treatment with midazolam versus nitrous oxide.Present findings, while tentative and based on secondary endpoints, suggest differential associations of nitrous oxide versus midazolam with bipolar depression severity and cerebral hemodynamics. Larger studies integrating neuroimaging targets and repeated nitrous oxide treatment sessions are warranted.
Abstract White matter hyperintensities (WMHs) are emblematic of cerebral small vessel disease, yet characterization at midlife is poorly studied. Here, we investigated whether WMH volume is associated with brain network alterations in midlife adults. 254 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study were selected and stratified by WMH burden yielding two groups of equal size (Lo- and Hi-WMH groups). We constructed group-level covariance networks based on cerebral blood flow (CBF) and grey matter volume (GMV) maps across 74 grey matter regions. Through consensus clustering, we found that both CBF and GMV covariance networks were partitioned into modules that were largely consistent between groups. Next, CBF and GMV covariance network topologies were compared between Lo- and Hi-WMH groups at global (clustering coefficient, characteristic path length, global efficiency) and regional (degree, betweenness centrality, local efficiency) levels. At the global level, there were no group differences in either CBF or GMV covariance networks. In contrast, we found group differences in the regional degree, betweenness centrality, and local efficiency of several brain regions in both CBF and GMV covariance networks. Overall, CBF and GMV covariance analyses provide evidence of WMH-related network alterations that were observed at midlife.
Abstract The long-term consequences of coronavirus disease 2019 (COVID-19) on brain physiology and function are not yet well understood. From the recently described NeuroCOVID-19 study, we examined cerebral blood flow (CBF) in 50 participants recruited to one of two groups: 1) adults who previously self-isolated at home due to COVID-19 (n = 39; 116.5 ± 62.2 days since positive diagnosis), or 2) controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (n = 11). Participants underwent arterial spin labeling magnetic resonance imaging at 3 T to yield measures of CBF. Voxel-wise analyses of CBF were performed to assess for between-group differences, after controlling for age and sex. Relative to controls, the COVID-19 group exhibited decreased CBF in the thalamus, orbitofrontal cortex, and regions of the basal ganglia. Within the COVID-19 group, CBF differences in occipital and parietal regions were observed between those with (n = 11) and without (n = 28) self-reported on-going fatigue. These results suggest long-term changes in brain physiology in adults across the post-COVID-19 timeframe. Moreover, CBF may aid in understanding the heterogeneous symptoms of the post-COVID-19 condition. Future longitudinal studies are needed to further characterize the consequences of COVID-19 on the brain.
White matter hyperintensities (WMHs) are emblematic of cerebral small vessel disease, yet effects on the brain have not been well characterized at midlife. Here, we investigated whether WMH volume is associated with brain network alterations in midlife adults. Two hundred and fifty-four participants from the Coronary Artery Risk Development in Young Adults study were selected and stratified by WMH burden into Lo-WMH (mean age = 50 ± 3.5 years) and Hi-WMH (mean age = 51 ± 3.7 years) groups of equal size. We constructed group-level covariance networks based on cerebral blood flow (CBF) and gray matter volume (GMV) maps across 74 gray matter regions. Through consensus clustering, we found that both CBF and GMV covariance networks partitioned into modules that were largely consistent between groups. Next, CBF and GMV covariance network topologies were compared between Lo- and Hi-WMH groups at global (clustering coefficient, characteristic path length, global efficiency) and regional (degree, betweenness centrality, local efficiency) levels. At the global level, there were no between-group differences in either CBF or GMV covariance networks. In contrast, we found between-group differences in the regional degree, betweenness centrality, and local efficiency of several brain regions in both CBF and GMV covariance networks. Overall, CBF and GMV covariance analyses provide evidence that WMH-related network alterations are present at midlife.
