Persistent post‐COVID headache is associated with suppression of scale‐free functional brain dynamics in non‐hospitalized individuals

Abstract

IntroductionPost‐acute coronavirus disease 2019 (COVID‐19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long‐term effects of COVID‐19 and post‐COVID headache on brain function remain poorly understood, particularly among non‐hospitalized individuals. This study focused on the power‐law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post‐COVID syndrome, with greatest reductions among those with persistent headache.MethodsResting‐state blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID‐19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu‐like symptoms but tested negative for COVID‐19. Individuals were assessed an average of 4–5 months after COVID testing, in a cross‐sectional, observational study design.ResultsNo significant differences in H values were found between non‐headache COVID‐19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non‐headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity.ConclusionsThese findings provide new insights into the neurophysiological mechanisms that underlie persistent post‐COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.

On the merits and potential of advanced neuroimaging techniques in COVID-19: A scoping review

“…Another study, focused on recovered COVID-19 patients around six months after hospital discharge, observed in comparison to healthy controls an increased ALFF (i.e., hyperactivity) in regions of the visual, language, and default mode network but decreased ALFF (i.e., hypoactivity) in regions of the paralimbic and executive network ( Li et al, 2023 ). A study in non-hospitalized COVID-19 patients four months after the infection observed altered functional brain dynamics – here characterized by the Hurst component, which is typically suppressed during physiological and psychological distress – in patients with persistent headache compared to patients without headache and healthy controls ( Churchill et al, 2023 ). Altered functional brain dynamics were particularly apparent in temporal, sensorimotor, and insular brain regions, and were accompanied by reduced functional connectivity and BOLD activity.…”

“…Conklin et al ( Conklin et al, 2021 ) previously described a distribution of lesions on SWI MRI images in critically ill COVID-19, which was found to be similar in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. From our search results, only four studies compared their findings in COVID-19 to other patient groups ( Sollini et al, 2021 , Kim et al, 2023 , Fischer et al, 2022 , Churchill et al, 2023 ), with one showing similarities to patients with traumatic brain injury (TBI) in terms of white matter alterations ( Fischer et al, 2022 ). However, compared to COVID-negative patients with flu-like symptoms, COVID-19 patients do show perfusion abnormalities ( Kim et al, 2023 ) and altered functional brain activity ( Churchill et al, 2023 ).…”

“…From our search results, only four studies compared their findings in COVID-19 to other patient groups ( Sollini et al, 2021 , Kim et al, 2023 , Fischer et al, 2022 , Churchill et al, 2023 ), with one showing similarities to patients with traumatic brain injury (TBI) in terms of white matter alterations ( Fischer et al, 2022 ). However, compared to COVID-negative patients with flu-like symptoms, COVID-19 patients do show perfusion abnormalities ( Kim et al, 2023 ) and altered functional brain activity ( Churchill et al, 2023 ). Moreover, it has been suggested that many COVID-19 patients present with unrelated comorbid findings of neurodegeneration and cerebrovascular disease ( Eschbacher et al, 2022 ), which may obscure reported findings.…”

Patients Recovering from COVID-19 who Presented Anosmia During their Acute Episode have Behavioral, Functional, and Structural Brain Alterations

“…Most studies investigating functional brain activity in patients recovered from COVID-19 have been conducted using resting-state methods. Alterations in signal properties and functional connectivity have been found in COVID-19 patients, 55,56 and have been associated with hospitalization, 57 and persistent symptoms such as headaches, 58 persistent olfactory dysfunction 48,59,60 and other behavioral markers such as working memory performance, 61,62 anxiety, 63 psychotic-like experiences in adolescents, 64 and post-traumatic stress symptoms. 65 Also, some studies found no functional alteration in recovered COVID-19 patients.…”