Sex-specific differences in resting-state functional connectivity of large-scale networks in postconcussion syndrome

Abstract

Concussions are associated with a range of cognitive, neuropsychological and behavioral sequelae that, at times, persist beyond typical recovery times and are referred to as postconcussion syndrome (PCS). There is growing support that concussion can disrupt network-based connectivity post-injury. To date, a significant knowledge gap remains regarding the sex-specific impact of concussion on resting state functional connectivity (rs-FC). The aims of this study were to (1) investigate the injury-based rs-FC differences across three large-scale neural networks and (2) explore the sex-specific impact of injury on network-based connectivity. MRI data was collected from a sample of 80 concussed participants who fulfilled the criteria for postconcussion syndrome and 31 control participants who did not have any history of concussion. Connectivity maps between network nodes and brain regions were used to assess connectivity using the Functional Connectivity (CONN) toolbox. Network based statistics showed that concussed participants were significantly different from healthy controls across both salience and fronto-parietal network nodes. More specifically, distinct subnetwork components were identified in the concussed sample, with hyperconnected frontal nodes and hypoconnected posterior nodes across both the salience and fronto-parietal networks, when compared to the healthy controls. Node-to-region analyses showed sex-specific differences across association cortices, however, driven by distinct networks. Sex-specific network-based alterations in rs-FC post concussion need to be examined to better understand the underlying mechanisms and associations to clinical outcomes.

Noninvasive magnetic resonance imaging techniques in mild traumatic brain injury research and diagnosis

“…The impairment of SN leading to functional imbalances within the network appear to affect cognitive control, and particularly may diminish self‐regulation of cognition, behavior and emotion (Peters, Dunlop, & Downar, 2016). Alterations in salience and fronto‐parietal networks connectivity in mTBI patients were highlighted in a study by Shafi et al (2020).…”

Sex-specific differences in resting-state functional brain activity in pediatric concussion

“…Only a few studies had samples that approached balance (40-45% female) with respect to sex distribution 15,19,20,23 , though these studies did not stratify their results by sex, instead providing group-level data comparing mixed-sex cohorts of children with concussion to their healthy peers. The most direct data on sex-specific rs-fMRI differences come from a recent study involving adults with PCS 24 . The lack of a sex-specific understanding of rs-fMRI differences in pediatric concussion is a considerable knowledge gap, given that sex, as a biological variable, has been recognized as an understudied yet important consideration in neuroscience 25-27 .…”

Investigating the Associations Between Brain Network Functional Connectivity and Health-Related Quality of Life Following a Pediatric Concussion

“…Due to the variation in FC strength throughout adolescence, age was included as a covariate in all analyses (Sherman et al, 2014). Sex was also covaried as reduced connectivity post-concussion was recently identified in females within and between multiple regions (Shafi et al, 2020). To account for the possibility of group differences between the PA and rest concussion groups, assigned groups were covaried.…”

“…Both crude linear regression and adjusted multivariate linear regression analyses were computed. The covariates used for the adjusted regression analyses included age (Sherman et al, 2014), sex (Shafi et al, 2020), randomization group (experimental or rest group), a composite diagnostic score (based on self-reported diagnoses of a learning disability, ADHD (Hilger & Fiebach, 2019), anxiety (Iverson et al, 2017;, depression (Iverson et al, 2017; and number of previous concussions (Plourde et al, 2020) and HBI total scores. The HBI total scores were covaried due to previous findings demonstrating the significant association between symptoms and HRQoL after concussion (Novak et al, 2016).…”

“…In addition, since the regression sample consists of only concussion participants, we chose only the most relevant variables that could influence our target population. Age and sex remained in the analysis as well due to the participant age range falling within an important developmental period for FC changes (Sherman et al, 2014) and due to the documented effects of sex on concussion recovery patterns and FC (Ledoux et al, 2019;Shafi et al, 2020).…”