Received: 18 September 2022 | Revised: 23 October 2022 | Accepted: 24 October 2022

DOI: 10.1111/cns.14028

ORIGINAL ARTICLE

Auditory–­limbic–­cerebellum interactions and cognitive

impairments in noise-­induced hearing loss

Xiao-­Min Xu1 | Yuan Feng1 | Jian Wang2 | Richard Salvi3 | Xindao Yin1 | Jun Gao4 |
Yu-­Chen Chen1

1
Department of Radiology, Nanjing First
Hospital, Nanjing Medical University, Abstract
Nanjing, China
Aims: This study aimed to explore the neural substrate of hearing loss-­related central
2
School of Human Communication
Disorders, Dalhousie University, Halifax,
nervous system in rats and its correlation with cognition.
Nova Scotia, Canada Methods: We identified the neural mechanism for these debilitating abnormalities by
3
Center for Hearing and Deafness, inducing a bilateral hearing loss animal model using intense broadband noise (122 dB
University at Buffalo, Buffalo, New York,
USA of broadband noise for 2 h) and used the Morris water maze test to characterize the
4
The Department of Neurobiology, behavioral changes at 6 months post-­noise exposure. Functional magnetic resonance
Key Laboratory of Human Functional
imaging (fMRI) was conducted to clarify disrupted functional network using bilateral
Genomics of Jiangsu, Nanjing Medical
University, Nanjing, China auditory cortex (ACx) as a seed. Structural diffusion tensor imaging (DTI) was applied
to illustrate characteristics of fibers in ACx and hippocampus. Pearson correlation was
Correspondence
Yu-­Chen Chen, Department of Radiology, computed behavioral tests and other features.
Nanjing First Hospital, Nanjing Medical
Results: A deficit in spatial learning/memory, body weight, and negative correlation
University, No.68, Changle Road, Qinhuai
District, Nanjing 210006, China. between them was observed. Functional connectivity revealed weakened coupling
Email: cycxwq@njmu.edu.cn
within the ACx and inferior colliculus, lateral lemniscus, the primary motor cortex, the
Jun Gao, Department of Neurobiology,
Key Laboratory of Human Functional
olfactory tubercle, hippocampus, and the paraflocculus lobe of the cerebellum. The
Genomics of Jiangsu, Nanjing Medical fiber number and mean length of ACx and different hippocampal subregions were
University, 101 Longmian Road, Jiangning
District, Nanjing 211166, China.
also damaged in hearing loss rats.
Email: gaojun@njmu.edu.cn Conclusion: A new model of auditory–­limbic–­cerebellum interactions accounting for

Funding information
noise-­induced hearing loss and cognitive impairments is proposed.
Doctoral Program of Entrepreneurship
and Innovation in Jiangsu Province, Grant/ KEYWORDS
Award Number: JSSCBS20211544; auditory cortex, cognitive impairment, hippocampus, limbic system, noise-­induced hearing loss
Nanjing Special Fund for Health Science
and Technology Development, Grant/
Award Number: YKK21133; Xinghuo
Talent Program of Nanjing First Hospital

1 | I NTRO D U C TI O N International Classification of Functioning and Disability provided,

hearing loss can affect body functions and structures (deteriora-
Hearing impairment is independently associated with a 30%–­4 0% tion in the ear), related activities (reduced speech understanding),
acceleration in cognitive decline, as well as an increased rate of and the participation of the individual in society (receiving educa-
all-­cause dementia.1 According to the framework 2 that WHO tion about health issues, attending social events, or receiving health

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

932 | 
wileyonlinelibrary.com/journal/cns CNS Neurosci Ther. 2023;29:932–940.
XU et al. | 933

services). It is reported that every 10 dB in hearing loss can lead to cycle. After 1-­
week acclimation, the animals were randomly as-
3
a 20% increased risk of developing dementia. The auditory cortex signed into the healthy controls (HCs) group (n = 13) and NIHL group
(ACx) is not only known as a major site for processing auditory in- (n = 13). A total of 12 control rats and 13 NIHL groups were left
formation and performing high functions of hearing but also related following 6 months. The animals were treated humanely and with
to cognition.4,5 Several evidence has proposed the relationship be- regard for alleviation of suffering.
tween hearing deprivation and cognitive impairment, but the caus-
ative connections remain to be confirmed.
Extreme noise exposure is a leading cause of acquired hearing 2.2 | Experimental design
loss6 and can be easily established in a quantity controllable manner
as compared with other methods. Prolonged exposure to intense At the baseline time, we recorded the body weight and Preyer's re-
sounds can induce moderate–­
severe sensorineural hearing loss flex (PR) of each rat that make sure all animals have normal hearing
characterized by the death of outer hair cells, inner hair cells, spiral abilities. After 1-­week acclimation, we conducted baseline MRI scan
ganglion neurons, and the auditory nerve fibers that project to the and measured the breath frequency during the same period. Then,
7 8
central auditory system. Our previous study has found anxious-­ we exposed the NIHL group to broadband intense noise (122 dB SPL)
and depression-­like behaviors in the early-­stage post-­noise, but the for 2 h. MWM task, auditory brainstem response (ABR) test, and MRI
long-­term effects of auditory deprivation in cognitive decline are scanning were done 6 months later, and one normal rat was dead of
poorly understood. Shortly after noise exposure, the role of oxida- anesthesia.
tive stress has been the focus in existing researches. However, the
independent influence of hearing loss and underlying neurological
mechanisms need to be substantiated. 2.3 | Noise exposure and auditory evaluation
Since Morris water maze (MWM) test does not require hearing
function, the decline in the performance suggests that hearing loss Auditory brainstem response test has been used for decades to as-
impairs the general function of the hippocampus.9 Moreover, there sess auditory function. This technique is non-­invasive and easy to
are close anatomic and functional connections between cognitive use, making it ideal for use in both clinical and experimental stud-
brain and the main nuclei in auditory pathway. Functional connec- ies. ABR waves are recorded far-­field from the scalp and are typi-
tivity (FC) is a powerful tool to study the considerable neural plas- cally comprised of five to seven vertex positive waves that appear
ticity in terms of whole brain. Functional connections are defined within the first 10 ms after an auditory stimulus.12 The procedures
as the temporal coincidence of neurophysiological events (including of noise exposure and ABR test were described in detail in our previ-
anatomical structure and functional associations) and effectively ous studies.8,13
describe information flow between brain areas.10 Additionally, dif-
fusion tensor imaging (DTI) can reveal microstructural changes in
white matter and has been widely used in animal models.11 2.4 | MWM test
In the present study, we used a broadband noise exposure for 2 h
(122 dB SPL) to establish noise-­induced hearing loss (NIHL) model. The water maze used in the present study was a black circular pool
Then, series of experiments (including MWM test, auditory func- with 160 cm in diameter and 60 cm in height, which was divided into
tion evaluation, and functional and structural MRI scanning) were four equal quadrants (I, II, III, and IV). An escape platform (11 cm in
conducted on rats in an aim to gain a more complete understanding diameter) was placed in the center of quadrant III, 1–­2 cm beneath
within and beyond the auditory pathway, as well as the neural mech- the surface of water. Consistent with other researches,14,15 this
anism of cognitive impairments following hearing deprivation. MWM test was comprised of spatial learning/training and memory
test. During the learning phase, each rat entered into the maze from
four different quadrants randomly for five consecutive days. On the
2 | M ATE R I A L S A N D M E TH O DS memory test day, the platform was removed from the maze and the
swimming paths in 90 s were recorded using a computer system with
2.1 | Animal models a video camera (AXIS-­90).

All animal procedures were conducted in accordance with the

National Institutes of Health Guide for the Care and Use of 2.5 | Functional MRI scanning and data analysis
Laboratory Animals and approved by the Animal Care Committee
of Nanjing Medical University, Nanjing, China. Twenty-­
six male A 7.0 T animal MRI scanner (PharmaScan, Bruker Biospin GmbH)
Sprague–­Dawley rats 4 weeks of age and weighing between 120 using a quadrature surface RF coil was used to acquire functional
and 150 g were used in this study (Qinglongshan Animal Center, and structural MRI data. Every rat was positioned in the scanner in
SCXK[ZHE]2014–­0 001). The colony room with ad libitum access to a prone position with a bite bar and two rods located on the left
food and water was maintained at 22°C with a 12:12-­h light/dark and right sides of the temporal surface of the head. The cotton
934 | XU et al.

TA B L E 1 Basic information on rats

Measurements NIHL group HCs group p-­value
used in each of the assessments.
Baseline
Number of rats (n) 13 13 /
Body weight (g) 135 ± 11 136 ± 9 0.852
Frequency of breath during MRI scanning 66 ± 11 65 ± 11 0.690
(n/min)
6 months post-­noise exposure
Number of rats (n) 13 12 /
Body weight (g) 457 ± 42 508 ± 31 0.002*
Frequency of breath during MRI scanning 55 ± 3 53 ± 3 0.272
(n/min)

Abbreviations: HCs, healthy controls; NIHL, noise-­induced hearing loss.

*p < 0.01.

was put in both ears to attenuate noise level from MRI scanning.
A temperature-­controlled water blanket was placed beneath the
rat to maintain the body temperature at 37.5°C. Animals were an-
esthetized with 5% isoflurane for 4 min firstly, then maintained
throughout scanning with 0.3% iso plus intramuscular injection of
the medetomidine (0.05 mg/kg). The respiration rates were moni-
tored by a Bruker Physiogard system with a sensor placed under the
animal's chest during the whole scanning procedure.
In order to keep the blood oxygenation level-­dependent (BOLD)
signal, heart beats, and respiration rates stable, MRI scanning started
1 h after the injection of anesthetic.16 The parameters of BOLD se-
quence were as follows: repetition time (TR) = 2000 ms; echo time
(TE) = 18 ms; slices = 21; filed of view (FOV) = 3.2 cm × 3.2 cm; num-
ber of averages = 1; matrix = 64 × 64; slice thickness/gap = 1/0 mm;
flip angle = 90°; and 100 volumes. The preprocessing steps were car-
ried out with statistical parametric mapping software (DPARBI_2.3,
http://rfmri.org/dpabi; SPM12, http://www.fil.ion.ucl.ac.uk/spm/),
including: (1) excluding first 10 times to allow for scanner calibra-
tion and adaptation to the environment; (2) skull stripping; (3) slice
timing; (4) realignment and correction for head motion; (5) spatial
normalization to the standard rat brain stereotaxic coordinates;
(6) detrending and filtering (0.01–­0.1 Hz); and (7) smoothing with
a full-­width at half-­maximum of 1 mm. Data with head movements
exceeded 0.1 mm of maximum translation in the x, y, or z directions
or 1.0 of maximum rotation about the three axes were discarded.
Subsequently, we chose the bilateral auditory cortex (ACx) as a seed
F I G U R E 1 Typical ABR waveforms in the NIHL group and HCs
to explore its functional connections with other auditory and non-­ group at 6 months post-­noise exposure. (A) Representative ABR
auditory brain regions. Two-­sample t-­test was performed to identify waveforms elicited by 8 kHz tone bursts presented at 90 dB SPL
significant changes in FC between NIHL and HCs groups and the in the HCs group. (B) Representative ABR waveforms elicited
thresholds were set at an uncorrected p-­value of p < 0.001 and clus- by 8 kHz tone bursts presented at 90 dB SPL in the NIHL group.
Note prominent, well-­defined peaks in the HCs group and barely
ter size >10 voxels.
detectable response in the NIHL group. ABR, auditory brainstem
response; HCs, healthy controls; NIHL, noise-­induced hearing loss.

2.6 | Data Acquisition and Imaging (DTI) analysis FOV = 3.2 cm × 3.2 cm; matrix = 128 × 128; slice thickness = 1 mm;
and 20 slices. Fiber tracking was computed using the TrackVis and
The DTI sequence was used to acquire 30 distinct diffu- Diffusion Toolkit software (http://www.track​vis.org). Regions of
sion directions and 5 reference images with the following pa- interest (ROI) drawing were obtained on direction-­encoded color
rameters: b-­value = 1000 s/mm2; TR = 2000 ms; TE = 23 ms; maps with sizes of 3 mm2 in bilateral ACx and subregions of the
XU et al. | 935

hippocampus (CA1 and CA2). The number of fibers and mean fiber fMRI data were not limited by instrumental noise, but by fluctua-
length in ROIs were evaluated. tions of biological origin, especially heartbeat and breathing.17
During our scanning, the frequency of breath between groups
showed no significance.
2.7 | Statistical analysis

Group differences in physiology measures and body weight were 3.2 | Bilateral hearing loss induced by
analyzed using the Student's t-­test. Additionally, to investigate the intense noise exposure
relationship between behavioral tests and body weight, the correla-
tion analysis was conducted using the Pearson correlation analysis A brief exposure to broadband noise at 122 dB SPL produced a
by SPSS software (version18.0; SPSS). A p < 0.05 was considered significant permanent threshold shift of moderate–­severe degree
statistically significant and Bonferroni correction for multiple com- as tested in the audiogram of ABR at 6 months post-­noise (6MPN)
parisons was applied in this analysis. (Table S1). Figure 1A,B represented the typical ABR waveforms of
HCs and NIHL rats, respectively. Compared with the HCs group, rats
post-­noise cannot lead waveform under different stimulus frequen-
3 | R E S U LT S cies, even 90 dB SPL.

3.1 | Basic characteristics of rats during the

experiments 3.3 | Group differences in hippocampal memory
in rats
The basic characteristics were detailed in Table 1. One rat was
excluded because of death which was induced by intolerable Spatial learning ability and memory were tested in an MWM
anesthesia. At baseline time, two groups were well matched for (Figure 2A). Figure 2B showed the escape latency in the training
number, age, gender, head motion, body weight, and frequency of session and no significance was observed. It was found that the
breath, and all rats had normal hearing. After noise exposure for platform crossing time of NIHL rats was less than HCs group in the
6 months, body weight showed a significant difference (p < 0.002). spatial orientation test period (p = 0.006, Figure 2C). In addition,
Unexpectedly, HCs group was heavier than the NIHL group, which rats in the NIHL group moved more than the HCs group in the target
meant the growth rate of weight was faster. It was reported that quadrant (SV III) on the test day (p = 0.018, Figure 2D).

F I G U R E 2 Weakened performance
underlying NIHL in MWM test. (A)
Schematic diagram of MWM. (B) Escape
latency of NIHL and HCs group during
training days. (C) Platform crossing time
on the test day. (D) Distance moved in SV
III on the test day. *p < 0.05; **p < 0.001.
HCs, healthy controls; MWM, Morris
water maze; NIHL, noise-­induced hearing
loss.
936 | XU et al.

3.4 | The alterations of functional connectivity 3.5 | Characteristics of fibers in auditory

present in rat brain cortex and hippocampus

The FC pattern is shown in Figure 3 and Table S2 (cluster size, At 6 months post-­
noise exposure, fiber number and mean fiber
and t-­v alues shown for the left and right hemispheres). Using length of bilateral ACx and right CA1 in NIHL were significantly less
the bilateral ACx as a seed, the NIHL group showed a signifi- than HCs group (Figure 4A–­F ). The mean fiber length of left CA1 and
cant bilateral decrease in FC in clusters located in the parafloc- right CA2 in the NIHL group was much lower than the HCs group
culus lobe of the cerebellum (PFL, 36 voxels), inferior colliculus (Figure 4H,J). We did not take the CA3 subregion into consideration
(IC, 11 voxels), lateral lemniscus (LL, 14 voxels), hippocampus because of its relatively small volume, and manual drawing led to
(17 voxels), the primary motor cortex (M1, 12 voxels), and olfac- certain deviations.
tory tubercle (Tu, 24 voxels), taking body weight as a covariance
(Figure 3A). Meanwhile, the two-­s ample t-­test reflected that ACx
showed weaker connectivity with PFL (10 voxels), agranular in- 3.6 | Correlation analysis between behavioral
sular cortex (AIP, 10 voxels), and hippocampus (30 voxels) in the tests and basic information
NIHL group without the covariance (Figure 3B). No increases
in FC were observed. Additionally, we tried to do a correlation A Pearson correlation analysis was performed to verify whether the
analysis between FC and behavioral measures, but no significant basic information is correlated with the outcome of MWM tests. A
results occurred. significantly negative correlation was observed between the body

F I G U R E 3 NIHL alters functional connectivity in specific brain regions using ACx as the seed. (A) The ACx shows weakened connections
with Tu, M1, HIP, LL, IC, and PFL using body weight as the covariance. Scale bar is shown in lower right; t-­values ranged from −5.64 to −3.79.
(B) The ACx shows decreased connections with AIP, HIP, and PFL using no covariance. Scale bar is shown in lower right; t-­values ranged from
−5.29 to −3.77. ACx, primary auditory cortex; AIP, agranular insular cortex; HIP, hippocampus; IC, inferior colliculus; LL, lateral lemniscus;
M1, primary motor cortex; NIHL, noise-­induced hearing loss; PFL, parafloccular lobe of cerebellum; Tu, olfactory tubercle. (p < 0.001,
uncorrected).
XU et al. | 937

weight and swimming distance in SV III in the spatial orientation ex- network signature, characterized by widely distributed, marked re-
periment for each NIHL individual (Figure 5, r = −0.646, p = 0.017). ductions in temporally coherent FC with the bilateral ACx, as well as
However, no other correlation relationships were obtained in the degraded structural fibers. By comparison, we reported weight loss
present study. in NIHL rats and the anticorrelation between body weight and behav-
ioral characteristics. The implications of these findings are elaborated
below, including the concept that network disruption associated
4 | DISCUSSION with cognitive decline reflects a unique neurobiological condition
of sensory-­deprived diseases, and the related idea that optimally
Mapping the borders between sensory-­deprived diseases and neu- healthy cognition is enabled by an active neuroadaptive trajectory.
rodegeneration has proved challenging for human research. In the Interestingly, the negative correlation between body weight
current study, NIHL rats with impaired memory exhibited a distinct and distance moved in SV III provided us with a new insight into

F I G U R E 4 Track alterations of bilateral ACx and hippocampal subregions underlying NIHL assessed by DTI technique. (A) Number
of fibers of right ACx; (B) Mean fiber length of right ACx; (C) Number of fibers of left ACx; (D) Mean fiber length of left ACx; (E) Number
of fibers of right CA1; (F) Mean fiber length of right CA1; (G) Number of fibers of left CA1; (H) Mean fiber length of left CA1; (I) Number of
fibers of right CA2; (J) Mean fiber length of right CA2; (K) Number of fibers of left CA2; (L) Mean fiber length of left CA2. Data are shown as
mean ± SEM. ACx, primary auditory cortex; DTI, diffusion tensor imaging; NIHL, noise-­induced hearing loss.
938 | XU et al.

The limbic system is involved in many emotions and motivations,

and the hippocampus is a major limbic region, receiving direct or in-
direct neural input from the central auditory system,32 functioning in
long-­term memory.33 In an odor-­place-­associated task, neural activ-
ity recorded from the entorhinal cortex (EC) and CA1 was thought to
depend on the interfacing of the hippocampus with inputs from the
olfactory bulb and piriform cortex via the EC.34,35 During encoding
and retrieval of declarative memories, entorhinal and hippocampal
circuits are thought to interact via theta and gamma oscillations,36
which in awake rodents predominate frequency spectra in both re-
gions. Since MWM has become the most extensively used protocol
to study hippocampus-­dependent spatial learning and memory in
rodents,37 decreased FC between ACx and hippocampus, Tu may
reveal the potential mechanism of NIHL-­induced cognitive impair-
ment. Although previous studies often report that early auditory
deprivation or congenital deafness contributes to cross-­modal re-
F I G U R E 5 Correlation between body weight and distance deprived cortex38 and aging-­
organization in the auditory-­ related
moved in SV III. Inserted lines are the results of linear regressions. hearing loss is strongly linked to cognitive impairment,39 few studies
were concerned about incident dementia induced by post-­lingually
the relationship between dementia and body weight. Human stud- hearing loss because of clinical benefits from cochlear prosthetics.
ies indicated that unintentional body weight loss was common in In the present study, we have detected the deficits of micro-
patients with dementia and is linked to cognitive impairment and structural integrity in ACx and HIP using DTI analysis. Mao et al.40
18
poorer disease outcomes, and it was an independent risk factor established a rat model of hearing loss and tinnitus by exposing to
for dementia-­related mortality.19,20 Moreover, body weight was also blast noise, then explored alterations to axonal and myelin integrity
found to contribute to predicted changes in hippocampal redox ratio, of auditory brain areas at 2 and 4 weeks following blast exposure.
21
especially in aging animals. There is a body of literature demon- Significant structural changes were found in the IC and medial genic-
strating selective aging-­related vulnerability to oxidative stress in ulate body, but not the ACx. Another rat model of conductive hear-
the hippocampus, suggesting that peripheral hearing loss and hip- ing loss only found the reduced lateral lemniscus (LL) fiber tract in
pocampal redox changes may share common mechanisms which the duration of 1 week.11 These inconsistencies with our findings are
are highly sensitive to metabolic insults. 22,23 These data pointed to probably due to the progression of hearing loss since our research
the possibility of using body weight as a window into the oxidative followed up for 6 months and tracked the process of brain remodel-
state of hippocampal neurons. Kim et al. 24 have evaluated the ef- ing underlying NIHL.
fects of body mass index on hearing loss in large amounts of adults The FC data suggested that hearing loss decreased functional
and found that the rates of hearing were significantly in underweight connections in a broad-­neural network that includes core auditory
and obese than in normal-­weight adults. Combining all, the causality structures extending from LL, through IC to ACx consistent with
link between hearing loss-­induced cognitive impairments and body previous studies implicating these central auditory structures in
weight is needed to be further investigated, and weight loss might be deafness.41,42 The IC of the auditory midbrain integrates the major-
a statistical marker of neurodegeneration and associated cognitive ity of ascending auditory information from lower brainstem regions.
decline. It receives prominent long-­range inhibitory input from the LL, a re-
fMRI has clear advantages for auditory characterizations and be- gion thought to be important for temporal pattern discrimination.43
comes a vital tool to characterize the auditory pathway in rodents, What is more, the FC between ACx and M1 was disrupted, which
as it is non-­invasive, provides relatively high spatial resolution, and may indirectly reflect neural plasticity. Although sensory and motor
lends itself to repetitive studies, albeit relying on an indirect neu- systems support different functions, both systems can exhibit topo-
rovascular coupling to deliver its information. 25,26 Recent findings graphic reorganization of the cortex following training or injury.44
have suggested that the Tu, in addition to receiving input from the Unexpectedly, our data expanded that PFL is involved in regulating
27
olfactory bulb, also serves to integrate reward and motivation in- hearing loss. The cerebellum is mainly involved in motor planning
formation from other limbic structures. 28,29 Taking account of its and control, and some cerebellar regions such as the PFL and vermis
morphology, chemistry, and anatomical connectivity, the Tu has a receive inputs from auditory centers.45
trilaminar structure containing distinct layers of neurons and is in- Our study also has some limitations. Firstly, we did not find any
terconnected with numerous brain regions, including neighboring correlations between MRI and behavioral tests, which may be due
cognitive and reward-­related limbic structures, such as the nucleus to the limited sample size. And we applied uncorrected p-­value in
accumbens and ventral pallidum as well as the olfactory bulb, the imaging analysis, as it is reported that a small sample size might con-
prefrontal cortex, thalamus, and hippocampus.30,31 tribute to a low signal-­to-­noise ratio and poor statistical power.11
XU et al. | 939

Future studies should expand it and address data quality. Secondly, 6. Panza F, Solfrizzi V, Logroscino G. Age-­ related hearing impair-
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1985;78:833-­860.
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rats post noise exposure. CNS Neurosci Ther. 2022;28:1547-­1556.
doi:10.1111/cns.13896
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date the neural patterns of NIHL-­associated cognitive impairments. L. Object recognition and Morris water maze to detect cognitive
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scientific advice; Xindao Yin helped with discussion and revision; 2021;15:655172. doi:10.3389/fnsys.2021.655172
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This work was supported in part by the Doctoral Program of tial learning or memory in the Morris water maze. Neurotox Res.
Entrepreneurship and Innovation in Jiangsu Province (JSSCBS20211544), 2021;39:1148-­1159. doi:10.1007/s12640-­021-­0 0355-­9
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Xinghuo Talent Program of Nanjing First Hospital, and Nanjing Special
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The authors declare that there is no potential conflict of interest re-
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garding the publication of this study. tional magnetic resonance imaging signal fluctuations in the human
brain at rest: a 7 T study. Magn Reson Imaging. 2009;27:1019-­1029.
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ORCID s40266-­017-­0 462-­x
Yu-­Chen Chen https://orcid.org/0000-0003-0468-6452 19. Strand BH, Wills AK, Langballe EM, Rosness TA, Engedal K,
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