Altered static and dynamic functional network connectivity in post-traumatic headache

DOI: https://doi.org/10.1186/s10194- 021- 01348- x

Abstract-Summary The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH.

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Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed.

The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), atten- tion network (AN), salience network (SN), visual network (VN), and cerebellum network (CN).

For sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs.

For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN.

Significant reduced connectivity changes in the DMN with VN was found in

State 4.

MTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a use- ful imaging biomarker for identifying and predicting mTBI with PTH.

Extended: The present study aimed to investigate the difference of sFNC and dFNC between the mTBI with and without PTH, using resting-state fMRI and sliding- window analysis.

The present study was approved by the local ethics of Nanjing Medical University. The present study combined sFNC and dFNC analyses to investigate the whole brain features of mTBI with PTH with a focus on the FNC states as well as the temporal properties.

MTBI patients with PTH provided detailed information about the headache, including the main location, headache intensity, and headache frequency (day/month).

MTBI patients with PTH have significantly different dFNC temporal properties

overall.

Introduction PTH can be attributed to mTBI or moderate or severe traumatic brain injury, and PTH is often accompanied by mood, cognitive autonomic and sleep symptoms [190]. The underlying neuropathological mechanism of PTH after mTBI still remains

unknown.

Significant FC differences between migraine and mTBI with persistent PTH were found [1, 7, 11, 19, 26, 30, 34, 37, 39, 40, 42, 56–192], and the altered func- tional network connectivity (FNC), such as DMN-attention network (AN) and VN-AN, were identified in mTBI patients [193].

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Post-concussion Syndrome

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These results suggest that network alterations reflect clinically relevant phenom-

ena in mTBI and mTBI with PTH.

Alterations in dFNC are still largely unknown in mTBI patients with PTH. The present study aimed to investigate the difference of sFNC and dFNC between the mTBI with and without PTH, using resting-state fMRI and sliding-window analysis.

We hypothesized that the sFNC, dFNC, and the temporal properties of dynamic

FC states would characterize the underlying nature of mTBI patients with PTH.

Materials and Methods Structural 3D T1-weighted images were acquired with the three- dimensional turbo fast-echo (3D-TFE) T1WI sequence with the following specifications: repetition time (TR)/echo time (TE) = 8.1/3.7 ms; slices = 170; gap = 0 mm; thickness = 1 mm; FA = 8°; FOV = 256 mm × 256 mm; and acquisition matrix = 256 × 256.

A single resting-state fMRI run lasted for 8  min and 10  s. The susceptibility weighted imaging (SWI) used a 3D gradient echo (GRE) sequence with the follow- ing parameters: TR/TE  =  22/34  mm; FA  =  20; slice thickness  =  1  mm; matrix = 276 × 319; and FOV = 220 mm × 220 mm.

After data preprocessing, the data of all subjects were analyzed using the spatial independent component analysis method implemented by GIFT software [194, 195], and the data were decomposed into functional networks showing unique time history characteristics.

Results The mean dwell time in state 1 was significantly shorter in mTBI  +  PTH group compared to mTBI-PTH group (mTBI  +  PTH: 9.13  ±  15.58; mTBI-PTH: 24.83 ± 34.09, p < 0.05).

The mean dwell time in state 4 was significantly longer in mTBI + PTH group compared with mTBI-PTH group (mTBI  +  PTH: 14.91  ±  21.93; mTBI-PTH: 5.96 ± 11.30, p < 0.05).

The number of transitions between states in mTBI + PTH group was smaller than in mTBI-PTH group (mTBI + PTH: 2.54 ± 2.22; mTBI-PTH: 3.64 ± 2.46, p < 0.05). We did not find any significant group differences in fractional windows in each

state (all p > 0.05).

Discussion The present study combined sFNC and dFNC analyses to investigate the whole brain features of mTBI with PTH with a focus on the FNC states as well as the temporal properties.

Our results revealed the sFNC and dFNC features and altered dynamic temporal properties, moreover, the temporal characteristics is associated with the headache measurements and cognitive performance in mTBI + PTH group.

We hypothesize that the association between hypersensitivity to pain and higher- order cortical cognitive control may be disrupted and as a whole involved in PTH following mTBI, and the results of FNC improve our understanding of the patho- physiological mechanisms of PTH in mTBI patients.

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This is a preliminary cross-sectional study of dFNC changes in PTH after mTBI, and the sample size is limited, making it difficult to directly infer a causal relation- ship between the brain functional network of PTH status and cognitive impairment after mTBI.

Conclusions This study explored for the static and dynamic FNC patterns in mTBI patients with PTH.

Compared to mTBI patients without PTH, the temporal properties of functional dynamics (number of transitions and dwelling time) were altered in mTBI patients with PTH, which were correlated with cognitive performance and headache characteristics.

Acknowledgement A machine generated summary based on the work of Li, Fengfang; Lu, Liyan; Shang, Song’an; Chen, Huiyou; Wang, Peng; Muthaiah, Vijaya Prakash; Yin, Xindao; Chen, Yu-Chen 2021 in The Journal of Headache and Pain.

Altered hypothalamic functional connectivity in post-traumatic headache after mild traumatic brain injury