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

David J Mikulis,Angela Colantonio,Reema Shafi,Robin E Green,Charles H Tator,Maria Carmela Tartaglia,Adrian P Crawley

doi:10.1038/s41598-020-77137-4

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.

Highlights

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)
The sample consisted of 80 individuals with postconcussion syndrome, 47 males with mean age ± SD = 32 ± 13 years and 33 females with mean age ± SD = 31.8 ± 13.1 years
We explored underlying alterations in both intra- and inter-network connectivity while exploring sex-specific changes in resting state functional connectivity (rs-FC) in long lasting PCS

Summary

Introduction

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). The dynamic synchronization of these n etworks[20] offers a unique opportunity to study complex network dynamics in the resting state Alterations in these three neural networks after TBI of various severity have been documented in the literature[21,22,23] and a large number of studies have explored network-related changes during the acute and subacute stages after concussion[24,25,26]. There are several definitions of PCS as was discussed r ecently[27], the criteria for a widely used definition include a history of TBI, cognitive deficits, presence of three of eight TBI symptoms (fatigue, sleep disturbance, headache, dizziness, irritability, affective disturbance, personality change, apathy) that began post-injury and persisted for ≥ 3 months post injury and are associated with social function interference[28]. We and others have previously used a month criterion[29]

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