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Brain Functional Alterations in Long-term Unilateral Hearing Impairment
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Original Research
Brain Functional Alterations in Longterm Unilateral Hearing Impairment Jianping Zhu, MM1, Jiangbo Cui, MM1, Gang Cao, BM, Jianwu Ji, MM, Xu Chang, MM, Chongjie Zhang, MM, Yongbo Liu, MD Background: The rate of patients with unilateral hearing impairments (UHI) increase with age and are characterized by asymmetric auditory afferents in which auditory information is asymmetrically transmitted to the brain. Long-term bilateral hearing imbalance can cause abnormal functional changes in the cerebral cortex. However, the relationship between functional alterations in the brain and the severity of the hearing impairment remains unclear. Methods: This study included 33 patients with UHI (left-sided impairment in 17 and right-sided impairment in 16) and 32 healthy patients. All participants underwent resting-state, blood oxygen level dependent functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuation (fALFF) values were calculated after data preprocessing and compared among the left-sided and right-sided impairment groups and the control group. Pure tone audiometry was used to evaluate patients’ hearing impairment level. The correlation between fALFF values of abnormal brain regions and the duration and severity of hearing impairment was analyzed. Results: Results provide evidence for altered resting-state functional activities in the brain of patients with left or right long-term UHI, with significantly increased fALFF values in the Heschl’s gyrus, superior temporal gyrus, and insula were observed. Moreover, complicated networks reorganization involved in the visual, cognitive, sensorimotor and information transmission functions except for the auditory function and some brain regions exhibited functional changes only in the one-sided impairment group. In addition, the severity of hearing impairment is related with the functional activities in the bilateral Heschl’s gyrus, bilateral insula, right superior temporal gyrus, and left middle frontal gyrus. Conclusion: In conclusion, alterations in functional activity are observed in the brains of patients with long-term hearing impairments and multiple brain regions within different functional networks are involved in the brain functional remodeling. The brain reintegration mechanism appears to be asymmetrical and the lateralization pattern in the contralateral brain hemisphere for auditory information processing related with the severity of hearing impairment. Key Words: Fractional amplitude of low frequency fluctuation; Hearing loss; Unilateral hearing impairment; Functional magnetic resonance imaging. © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
INTRODUCTION
T
he incidence of unilateral hearing impairment (UHI) increases with age and is characterized by asymmetric auditory afferents where auditory information is asymmetrically transmitted to the brain (1,2). Recognition and processing of auditory information are advanced functions in the human brain, implying that the underlying mechanisms of hearing impairments are complex (3,4). Hearing imbalance can cause poor sound localization and difficulty in
Acad Radiol 2019; &:1–8 From the Department of Imaging, Heping Hospital affiliated to Changzhi Medical College, Changzhi, PR China (J.Z., J.J.); Department of Imaging, Hepji Hospital affiliated to Changzhi Medical College, Changzhi, PR China (J.C.); Department of radiology, Peking University Lu’an Hospital, Changzhi, PR China (G.C., Y.L.); Graduate School of Changzhi Medical College, Changzhi, PR China (X.C.); Department of Imaging, Yuncheng Central Hospital, Yuncheng, PR China (C.Z.). Received August 11, 2019; revised September 13, 2019; accepted September 18, 2019. Address correspondence to: Y.L. e-mail: [email protected] 1 These authors contributed equally. © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.acra.2019.09.027
directional hearing, and long-term UHI can result in cerebral functional alterations and reorganization (5,6). Functional magnetic resonance imaging (fMRI) studies have been performed on patients with hearing impairments providing valuable insights into associated auditory information processing and functional integration mechanisms of the brain. Neurons encode binaural time or intensity signals by converting them into information about spatial characteristics in order to obtain the spatial location of sound. In addition, binaural information integration can also help to interact with brain function activity, which can maintain the relative acoustic stability in a certain background of stimulus parameters (7). The auditory cortex responsible for auditory function is located in the upper medial fissure of bilateral temporal lobe and includes the Heschl’s gyrus (HG) and part of the temporal gyrus (8). Studies have shown that patients with UHI exhibit psychological changes, which may result from functional activity changes in some brain regions including the right supramarginal gyrus, bilateral thalamus, and prefrontal lobe (9 11). Moreover, fMRI has shown that patients with UHI exhibit cortical functional remodeling of bilateral transverse temporal gyrus because of unilateral auditory
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stimulation and bilateral imbalance of auditory conduction (12,13). In such instances, the impaired side significantly affects the corresponding lateralization pattern and results in hemispheric dominance of auditory processing in the auditory functional network. While studies have begun to highlight functional changes in UHI, the exact association between unilateral auditory input patterns and auditory activity alterations of corresponding brain regions are still being explored (14 17). Amplitude of low frequency fluctuation (ALFF) can be calculated with the square root of power spectrum integrated in a low-frequency range (frequency range of 0 0.1 Hz) and it is an index used for detecting the regional intensity of spontaneous fluctuations in blood oxygen-level dependent signal of resting state functional MRI (18). Fractional ALFF (fALFF) is a methodological improvement of ALFF, denoted as the power within the low-frequency range divided by the total power in the entire frequency range (19). Both ALFF and fALFF reflect functional activities in the brain in the form of energy metabolism. Although previous neuroimaging studies have shown that certain brain regions related to auditory functions may be altered in patients with hearing impairments, fALFF studies on UHI are rare and the relationship between fALFF and the severity of hearing impairments remains unclear (20,21). Previous neuroimaging studies (22,23) also observed differences in abnormal brain activities in patients between left and right UHI. However, for patients with left or right long-term UHI, it is unclear whether there are bilateral fALFF differences along with abnormal functional activities. Therefore, we used fALFF to evaluate the functional alterations in patients with longterm UHI in order to identify the brain regions with abnormal functional activities in patients with left or right long-term UHI, respectively. In this study, we hypothesize that UHI leads to functional activity changes in certain regions of the brain and that intrinsic brain reintegration mechanisms will be different in patients with left- and right-sided hearing impairment. In addition, their altered brain functional activities correlate with the degree of hearing impairment. fALFF under resting-state fMRI was used to evaluate functional activities in the brains of healthy control and UHI patient groups. Differences in fALFF among the control group and patients with left or right UHI were compared and analyzed, respectively. Moreover, correlation analysis between quantitative fALFF, and the duration and severity of UHI was performed in the UHI group.
MATERIALS AND METHODS Participants
Thirty-three patients with UHI caused by idiopathic hearing loss were recruited for this study (20 male, 13 female, aged 24 55 years, mean age: 44.31 § 10.13), including 17 patients with left-sided hearing impairments and 16 patients with right-sided hearing impairments. All patients had been diagnosed with unilateral chronic hearing loss for at least 2 years. In addition, 32 healthy individuals (18 male, 14 2
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female, aged 22 58 years, mean age: 45.86 § 13.28) were recruited as the control group. Pure tone audiometry (PTA) was used to evaluate patients’ hearing level. Hearing thresholds of 500 kHz, 1000 kHz, 2000 kHz, and 4000 kHz were used to calculate the average PTA values in participants. All patients were diagnosed with moderate to severe impairments in one ear with PTA value of >40 dB HL, while all healthy ears and the control group had ''normal hearing'' at a PTA value of 25 dB HL. All participants were right-handed and patients with any of the following conditions were excluded: pregnancy, neurological diseases, poorly controlled hypertension, psychiatric disorders, history of heart disease, recent head injury, metabolic diseases, or any other condition that could affect the study. This study was approved by the hospital’s academic ethics committee and informed consent was obtained from all participants. Data Acquisition
A 3.0 T superconducting magnetic resonance scanner (MAGNETOM Skyra, German) with matched receiver coil and parallel imaging system was employed for MRI examination. All participants were asked to lie still, close their eyes, breathe calmly, and minimize head movements. Meanwhile, bilateral rubber earplugs and electrostatic headphones were given to reduce scanner noise and all participants were asked to refrain from sleeping and refrain from thinking about. First, localized images were obtained, following which conventional axial T2-weighted imaging was performed to exclude any organic lesions in the brain. Resting state fMRI was performed with an axial echo-planar imaging (GRE-EPI) sequence, using a single-shot acquisition technique (slice thickness = 3.5 mm, slice interval = 0.7 mm, repetition time (TR) = 2000 ms, echo time (TE) = 30 ms, inversion angle = 90°, matrix = 64 £ 64, field of view (FOV) = 240 £ 240 mm2, and number of excitations (NEX) = 1, 34 slices and 250 time points). Finally, a sagittal structural 3D T1-weighted image was collected using a 3D T1-weighted image with 3-dimensional fast spoiled gradientecho sequences (thickness =1 mm, TR = 6.7 ms, TE = min full, matrix = 256 £ 256, FOV = 256 £ 256 mm2, NEX = 1). Data Processing and Analysis
Data Preprocessing Data preprocessing was carried out using Data Processing Assistant for Resting-State fMRI (DPARSF, Advanced Edition). Preprocessing included data format conversion (from DICOM to NIFTI format), removal of the first five time points and slice-time correction. Head motion correction was carried out with a standard of 2 mm or 2°, and six motion parameters (three translation and three rotation) were obtained. Spatial standardization was performed. Functional images were coregistered with corresponding T1 structural images that were segmented and warped into the anatomical Montreal Neurological Institute template; they were then transformed at a resolution of 3-mm isotropic resolution into
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the standard Montreal Neurological Institute space. Spatial smoothing was performed with the full-width half-maximum was set to 4. Linear drift was removed and covariate regression was performed, and the white matter, cerebrospinal fluid signals, global signals, and six head-motion parameters were eliminated. Finally, Band-pass filtering was performed (0.01 0.08 Hz) to remove the effects of low-frequency drifts and high-frequency noise after fALFF calculation (24). fALFF Computation and Statistical Analysis fALFF values from resting state functional MRI were analyzed using Resting-State fMRI Data Analysis Toolkit v1.8 software (https://sourceforge.net/projects/resting-fmri). The time series of each voxel obtained from preprocessed data were converted to the frequency domain by a fast Fourier transform, and the square root of the power spectrum was computed as the ALFF. The ALFF value was then further divided by the global mean ALFF value to standardize the data within each group. The normalized ALFF value was divided by the ALFF value of the entire band to obtain the normalized fALFF value of each voxel. The differences between fALFF brain-maps from UHI and controls groups were compared using a two-sample t test, with covariance factors of sex, age, education level, and six head-movement parameters. Results were corrected using false discovery rate correction and p values were considered statistically significant at <0.05. The brain fALFF values at voxel level were extracted. These were used for Pearson’s correlations analysis with the PTA scores and the duration of hearing impairments, the differences were considered statistically significant if p < 0.05. RESULTS Clinical Data
There were no significant differences in sex, age, and educational level among UHI patient groups and healthy control groups (p > 0.05). The average duration and PTA of the affected ear in all patient groups were calculated (duration: mean 37.9 § 11.68 months and PTA: mean 67.4 § 18.75 dB HL in left-sided impairment; mean 36.88 § 10.29 months
and PTA: mean 68.5 § 21.22 dB HL in right-sided impairment). Moreover, the healthy side of patients, and both sides of the control group exhibited normal hearing ability (PTA 20 dB HL) (Table 1). fALFF Differences Between UHI Groups and Control Group
The left UHI group exhibited significantly higher fALFF values in the right HG, left inferior parietal lobule (IPL), right superior temporal gyrus (STG), left angular gyrus, right superior parietal gyrus (SPG), right precentral gyrus (PreCG), and right insula, compared with the control group. Furthermore, left UHI patients had significantly lower fALFF values in the right supplementary motor area (SMA) compared with the control groups (Table 2, Figure 1). The right UHI group exhibited significantly higher fALFF values in the left superior frontal gyrus, left HG, bilateral STG, bilateral middle frontal gyrus (MFG), right postcentral gyrus (postCG), left triangular part of inferior frontal gyrus (IFGtri), and left insula, compared with the control group (Table 3, Fig 2). Correlations Between Abnormal fALFF and PTA and UHI Duration
No significant correlation was found between fALFF values and duration of UHI. However, in the left UHI group, fALFF values positively correlated with PTA in the right HG (p< 0.01, r = 0.71) and right STG (p< 0.01, r = 0.74). Moreover, fALFF values negatively correlated with the PTA in the right insula (p< 0.01, r = 0.68) (Table 4, Fig 3). In the right UHI group, fALFF values positively correlated with PTA in the left HG (p < 0.01, r = 0.72) and left middle frontal gyrus (p < 0.01, r = 0.63). Moreover, fALFF values were negatively correlated with the PTA in the left insula (p< 0.05, p= 0.57) (Table 4, Fig 3). DISCUSSION In this study, fALFF values were used to evaluate resting-state changes in the functional activity of the brain in patients with
TABLE 1. Demographic and Clinical Data of Unilateral Hearing Impairment Patients and Healthy Controls All Patients (33) Protocols
Left Side(17)
Right Side(16)
HCs (32)
p Value
Gender (M/F) Age (y) Education (y) Duration (mo) PTA of affected ear (dB HL) PTA of normal ear (dB HL)
10/7 45.27 § 11.05 11.15 § 2.47 37. 9 § 11. 68 67.4 § 18.75 25
9/7 43.19 § 9.82 9.83 § 1.67 36. 88 § 10. 29 68.5 § 21.22 25
18/14 45.86 § 13.28 11.76 § 3.18 / / 25
0.34a 0.125b 0.238b 0.357c 0.326c /
HCs, healthy control patients; PTA pure tone audiometry. p Value was obtained using a Pearson chi-square test (two-tailed) among three groups. b p Value was obtained using one-way analysis of variance among three groups. c p Value was obtained using independent two samples t test between two groups. a
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TABLE 2. Brain Regions Showing Intergroup fALFF Differences Between Left Hearing Impairment and Healthy Control Groups
Brain Regions
BA
Peak MNI Coordinates (mm) (x, y, z)
HG.R IPL.L STG.R AG.L SPG.R PreCG.R SMA.R Insula.R
48 7 21 39 40 4 6 48
(52, 11, 7) ( 32, 57, 46) (59, 0, 10) ( 42, 65, 35) (42, 45, 60) (52, 8, 45) (7, 4,52) (42,4, 1)
t Value 2.72 3.48 2.55 2.43 2.88 3.36 3.53 3.26
AG.L, left angular gyrus; BA, Brodmann area; HG.R, right Heschl’s gyrus; Insula.R, right insula; MNI, Montreal Neurologic Institute; PL. L, inferior parietal lobule; PreCG.R, right precentral gyrus; SMA.R, right supplementary motor area; SPG.R, right superior parietal gyrus; ISTG.R, right superior temporal gyrus.
chronic UHI. fALFF is a relative ratio which is related to the total value and fluctuation amplitude value (18). At present, there is no study to measure the normal value level in large scalar group. In a small sample study the intergroup differences and statistical differences depend on the extent of differences between patients and healthy subjects (19). Previous study by Schmithorst et al. (25) showed that cortical remodeling occurs in patients with UHI for at least 2 years. Hence, this study included patients with a history of hearing impairment for at least 2 years. Significantly higher fALFF values were observed in the HG, STG, and insula in the UHI groups when compared with the control group. HG, also called the transverse temporal gyrus, is the primary cortical structure that processes auditory inputs and is shown to be active during tone and semantic tasks using fMRI (26). HG has been found to have significantly faster processing rates (33 Hz) in the left hemisphere than in the right hemisphere (3 Hz) (27). Additionally, the difference in processing rates was found to correlate with the volume of rate-related cortex in the HG, while the right HG is shown to be more active during auditory information processing than the left HG (28). The STG, in addition to its function in language processing, is an essential structure in auditory processing, and is involved
TABLE 3. Brain Regions Showing Intergroup fALFF Differences Between Right Hearing Impairment and Healthy Control Groups
Brain Regions
BA
Peak MNI Coordinates (mm) (x, y, z)
SFG.L HG.L STG.L STG.R MFG.L MFG.R PostCG.R IFGtri.L Insula.L
46 48 21 21 46 48 3 45 48
( 25, 53, 24) ( 48, 13, 7) ( 54, 0, 11) (57, 0, 6) ( 27, 37, 29) (29, 32, 19) (52,-19,40) ( 44,32,20) ( 40,1, 1)
t Value 2.66 3.27 2.47 2.35 2.74 2.83 3.45 2.64 3.15
BA, Brodmann area; HG.L, left Heschl’s gyrus; IFGtri.L, left triangular part of inferior frontal gyrus; Insula.L, left insula; MFG.L, left middle frontal gyrus; MFG.R, right middle frontal gyrus; MNI, Montreal Neurologic Institute; PostCG.R, right postcentral gyrus; SFG.L, left superior frontal gyrus; STG.L, left superior temporal gyrus; STG.R, right superior temporal gyrus.
in the processing of auditory information related to facial expressions (29). Moreover, research conducted with fMRI showed a link between insight-based problem solving and brain activity, specifically related to sudden auditory information (30). The STG is also involved in the perception of emotions in facial stimuli (31,32). The insula is involved in multimodal sensory processing, and functional imaging studies (33,34) have shown the activation of the insula during audio-visual integration tasks, indicating that the insula may be involved in the interactive remodeling of the auditory and visual functional network. Interestingly, in this study, some brain regions exhibited functional changes only in the one-sided impairment group. Abnormal fALFF values were observed in the IPL, angular gyrus, SPG, SMA, and PreCG only in the left-sided group. The SPG is involved in spatial orientation, receiving enormous amounts of visual and sensory input (35). While the IPL and angular gyrus are related to the perception of facial emotions as well as language comprehension and production (35). Furthermore, the PreCG and SMA are related to the prominent gyrus in the somatic motor cortex, usually described as the main and supplementary
Figure 1. Brain regions showed fALFF differences between left hearing impairment and healthy control groups. The abnormal regions with higher fALFF were observed in the right Heschl’s gyrus (HG), left inferior parietal lobule (IPL), right superior temporal gyrus (STG), left angular gyrus (AG), right superior parietal gyrus (SPG), right precentral gyrus (PreCG), and right insula. The regions with lower fALFF were observed in the right supplementary motor area (SMA) as compared with healthy controls.
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Figure 2. Brain regions showed fALFF differences between right hearing impairment and healthy control groups. The abnormal regions with higher fALFF were observed in the left superior frontal gyrus (SFG), left Heschl’s gyrus, bilateral superior temporal gyrus, bilateral middle frontal gyrus (MFG), right postcentral gyrus (postCG), left triangular part of inferior frontal gyrus (IFGtri), and left insula.
area for motion (36). SMA is the only brain region related to motor function and was found to be negatively active in our study. The SMA exists in an overlapping somatotopic arrangement, found on the contralateral side of the brain to the corresponding body parts. As a result, in patients with UHI, functional activity of SMA was relatively lower on the contralateral side to impaired hearing than the ipsilateral side. Previous studies have suggested that perceptual compensation allows individuals to obtain sufficient information about the environment, by perceiving stimuli that are suitable for their own sensory patterns (24). For example, a study using magnetoencephalography found that visual areas in blind individuals are used to perform auditory functions (37). Therefore, the altered activity of these nonauditory areas in patients with UHI may support the perceptual compensation theory (38,39). Abnormal fALFF values were observed in the superior frontal gyrus, middle frontal gyrus, postcentral gyrus, and triangular part of inferior frontal gyrus only in the right-sided group. Among these regions, the frontal cortex is extremely important for language comprehension and production, and it has also been shown to play a role in inhibitory processes, including inhibiting learning of undesirable information (40). Furthermore, the postcentral gyrus is a prominent gyrus in the primary somatosensory cortex, usually described as the main sensory receptive area for touch (41,42). Comparison of auditory and visual processing showed that extensive brain areas were activated in both the parietal lobes and the inferior frontal gyrus, when integrating auditory and visual information. The abnormal functional activity of these brain areas in the present study suggests that brain reorganization mechanisms may occur in UHI patients with neurological deafness (43). However, the findings of this study are not entirely
consistent with previous literature. In previous studies, altered functional activities were found in the supramarginal gyrus of patients with hearing impairments (44 47). However, in this study, no significant differences were found in the supramarginal gyrus between UHI patients and the control groups (24). Furthermore, a previous study (34) showed that patients with rightsided hearing impairment showed abnormal fALFF alteration in the precuneus, and middle and inferior temporal gyrus, which showed no significant differences in our study. Previous studies inferred that the brain’s functional network may undergo neuroplastic changes during different physiological conditions, to adapt to the needs of the surrounding environment (23). Moreover, our results indicate that reorganization mechanisms are further complicated by the integration of different brain functional activities besides auditory function in the brain of UHI patients. On the other hand, abnormal fALFF values and the duration of UHI showed no significant correlations, indicating that the stages of the disease, shown in this study, do not affect brain function remodeling. However, both sides of HG, the right STG, and the left middle frontal gyrus showed positive correlations with PTA values in the impairment groups. These results highlight the role of HG, the STG, and the middle frontal gyrus in processing auditory inputs (48) and suggest that the relative activity of auditory functions in the left and right hemispheres are related to the severity of UHI. In contrast, regions showing negative correlations with PTA, were the bilateral insulae. The insular cortex is involved in multimodal sensory processing (33). Functional imaging studies show that the insular lobe is activated in audiovisual integration tasks and insular lobe is therefore involved in the interactive remodeling of
TABLE 4. Brain Regions Showed Correlation with PTA in Hearing Impairment Groups Group
Brain Regions
Correlation with
Left hearing impairment
HG.R STG.R Insula.R HG.L MFG.L Insula.L
PTA PTA PTA PTA PTA PTA
Right hearing impairment
r Values 0.71 0.74 0.68 0.72 0.63 0.57
p Values 0.001 0.001 0.002 0.001 0.009 0.02
HG.R, right Heschl’s gyrus; Insula.L left insula; Insula.R, right insula; MFG.L, left middle frontal gyrus; STG.R, right superior temporal gyrus.
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Figure 3. Correlations between altered fALFF values (vertical axis) of brain regions and corresponding PTA scores (transverse axis) of the patients. (A) The fALFF values that positively correlated with the PTA were the right Heschl’s gyrus (HG) and superior temporal gyrus (STG), and negatively correlated with the PTA were the right insula in the patients with left hearing impairment. (B) The fALFF values that positively correlated with the PTA were the left Heschl’s gyrus (HG) and middle frontal gyrus (MFG), and negatively correlated with the PTA were the left insula in the patients with right hearing impairment.
auditory and visual functional networks (34). We can speculate that auditory processing is related to information transmission to the contralateral hemisphere and that a decrease in auditory activity indicates a higher severity of UHI. These results correspond with those from previous studies (49) showing that the contralateral hemisphere exhibits brain lateralization for processing auditory information. This study has limitations. First, the sample size was relatively small and therefore the validity of statistical inference is low. Second, although, earplugs and electrostatic headphones were given to participants during fMRI scanning, the noise of the MRI scanner could not be completely eliminated. Finally, patients with UHI were not segregated based on etiology. Therefore, to verify the reliability of the results, in the future we should have to increase the sample size, use etiological grouping to differentiate between causes of the disorder, and apply methods to eliminate the impact of MRI noise.
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CONCLUSION This study provides significant evidence for altered resting-state functional activities in the brain of patients with left or right long-term UHI. Significantly increased fALFF values were observed in the HG, STG, and insula in both left- and rightsided UHI groups. Moreover, some brain regions exhibited functional changes only in the one-sided impairment group. Complicated network reorganization was seen in regions of the brain involved visual, cognitive, sensorimotor and information transmission functions besides the auditory function in the UHI patients. In addition, it is the severity of hearing impairment and not the duration of UHI which is associated with functional activity in different brain regions. In conclusion, multiple brain regions within different functional networks were involved in the brain functional remodeling for UHI patients. The altered functional activities in certain brain regions are not symmetrical and the lateralization pattern in
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the contralateral brain hemisphere for auditory information processing is related to the severity of hearing impairment.
AUTHOR CONTRIBUTIONS Jiangping Zhu and Jiangbo Cui contributed equally, they acquired and analyzed data, drafted the manuscript, and revised it. Gang Cao, Xu Chang, Jianwu Ji, and Chongjie Zhang analyzed and explained the data, and checked the data. Yongbo Liu revised the manuscript for extremely important intellectual content.
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19. Jing B, Liu CH, Ma X, et al. Difference in amplitude of low-frequency fluctuation between currently depressed and remitted females 323 with major depressive disorder. Brain Res 2013; 1540:74–83. 20. Pross SE, Chang JL, Mizuiri D, et al. Temporal cortical plasticity in singlesided deafness: a functional imaging study. Otol Neurotol 2015; 36:1443–1449. 21. Zhang Y, Mao Z, Feng S, et al. Altered functional networks in long-term unilateral hearing loss: a connectome analysis:. Brain Behav 2018; 8(2): e00912. 22. Burton H, Firszt JB, Holden T, et al. Activation lateralization in human core, belt, and parabelt auditory fields with unilateral deafness compared to normal hearing. Brain Res 2012; 1454:33–47. 23. Zhang Y, Mao Z, Feng S, et al. Monaural-driven functional changes within and beyond the auditory cortical network: evidence from longterm unilateral hearing impairment. Neuroscience 2018; 371:296–308. 24. Xie X, Liu Y, Han X, et al. Differences in intrinsic brain abnormalities between patients with left-and right-sided long-term hearing impairment. Front Neurosci 2019;13:206. doi: 10.3389/fnins.2019.00206. 25. Schmithorst VJ, Plante E, Holland S. Unilateral deafness in children affects development of multi-modal modulation and default mode networks. Front Hum Neurosci 2014; 8:164. 26. Warrier C, Wong P, Penhune V, et al. Relating structure to function: Heschl's gyrus and acoustic processing. J Neurosci 2009; 29:61–69. 27. Shah J, Pham GN, Zhang J, et al. Evaluating diagnostic yield of computed tomography (CT) and magnetic resonance imaging (MRI) in pediatric unilateral sensorineural hearing loss. Int J Pediatr Otorhinolaryngol 2018; 115:41–44. 28. Deal JA, Goman AM, Albert MS, et al. Hearing treatment for reducing cognitive decline: Design and methods of the Aging and Cognitive Health Evaluation in Elders randomized controlled trial. Alzheimers Dement (N Y) 2018; 5:499–507. 29. Pan P, Huang J, Morioka C, et al. Cost analysis of vestibular schwannoma screening with contrast-enhanced magnetic resonance imaging in patients with asymmetrical hearing loss. J Laryngol Otol 2016; 130(1):21–24. 30. Zhang Y, Mao Z, Feng S, et al. Convergent and divergent functional connectivity patterns in patients with long-term left-sided and right-sided deafness. Neurosci Lett 2017; 665:74–79. 31. Bigler ED, Mortensen S, Neeley ES, et al. Superior temporal gyrus, language function, and autism. Dev Neuropsychol 2007; 31(2):217–238. 32. Radua J, Phillips ML, Russell T, et al. Neural response to specific components of fearful faces in healthy and schizophrenic adults. Neuroimage 2010; 49(1):939–946. 33. Bushara KO, Grafman J, Hallett M. Neural correlates of auditory-visual stimulus onset asynchrony detection. J Neurosci 2001; 21(1):300–304. 34. Yang M, Chen HJ, Liu B, et al. Brain structural and functional alterations in patients with unilateral hearing loss. Hear Res 2014; 316:37–43. 35. Kamali A, Sair HI, Radmanesh A, et al. Decoding the superior parietal lobule connections of the superior longitudinal fasciculus/arcuate fasciculus in the human brain. Neuroscience 2014; 277:577–583. 36. Rizzolatti G, Sinigaglia C. The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations. Nat Rev Neurosci 2010; 11(4):264–274. 37. Inui H, Sakamoto T, Ito T, et al. Magnetic resonance-based volumetric measurement of the endolymphatic space in patients with Meniere's disease and other endolymphatic hydrops-related diseases. Auris Nasus Larynx 2018; 29. pii: S0385-8146(18)30860-5. 38. Tan L, Chen Y, Maloney TC, et al. Combined analysis of SMRI and FMRI imaging data provides accurate disease markers for hearing impairment. NeuroImage: Clinical 2013; 3:416–428. 39. Husain FT, Pajor NM, Smith JF, et al. Discrimination task reveals differences in neural bases of tinnitus and hearing impairment. Plos One 2011; 6 (10):e26639. 40. Khan HZ, Park CY, Lim MA, et al. Radiographic findings in young adults with asymmetric sensorineural hearing loss. Am J Otolaryngol 2018; 11. pii: S0196-0709(18)30828-7. 41. Boudewyns A, Declau F, van den Ende J, et al. Auditory neuropathy spectrum disorder (ANSD) in referrals from neonatal hearing screening at a well-baby clinic. Eur J Pediatr 2016; 175(7):993–1000. 42. Conte G, Di Berardino F, Sina C, et al. MR imaging in sudden sensorineural hearing loss. time to talk. AJNR Am J Neuroradiol. 2017; 38(8):1475–1479. 43. Wang X, Xu P, Li P, et al. Alterations in gray matter volume due to unilateral hearing loss. Sci Rep 2016; 6:25811. 44. Paul A, Marlin S, Parodi M, et al. Unilateral sensorineural hearing loss: medical context and etiology. Audiol Neurootol 2017; 22(2):83–88.
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Original Research
Brain Functional Alterations in Longterm Unilateral Hearing Impairment Jianping Zhu, MM1, Jiangbo Cui, MM1, Gang Cao, BM, Jianwu Ji, MM, Xu Chang, MM, Chongjie Zhang, MM, Yongbo Liu, MD Background: The rate of patients with unilateral hearing impairments (UHI) increase with age and are characterized by asymmetric auditory afferents in which auditory information is asymmetrically transmitted to the brain. Long-term bilateral hearing imbalance can cause abnormal functional changes in the cerebral cortex. However, the relationship between functional alterations in the brain and the severity of the hearing impairment remains unclear. Methods: This study included 33 patients with UHI (left-sided impairment in 17 and right-sided impairment in 16) and 32 healthy patients. All participants underwent resting-state, blood oxygen level dependent functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuation (fALFF) values were calculated after data preprocessing and compared among the left-sided and right-sided impairment groups and the control group. Pure tone audiometry was used to evaluate patients’ hearing impairment level. The correlation between fALFF values of abnormal brain regions and the duration and severity of hearing impairment was analyzed. Results: Results provide evidence for altered resting-state functional activities in the brain of patients with left or right long-term UHI, with significantly increased fALFF values in the Heschl’s gyrus, superior temporal gyrus, and insula were observed. Moreover, complicated networks reorganization involved in the visual, cognitive, sensorimotor and information transmission functions except for the auditory function and some brain regions exhibited functional changes only in the one-sided impairment group. In addition, the severity of hearing impairment is related with the functional activities in the bilateral Heschl’s gyrus, bilateral insula, right superior temporal gyrus, and left middle frontal gyrus. Conclusion: In conclusion, alterations in functional activity are observed in the brains of patients with long-term hearing impairments and multiple brain regions within different functional networks are involved in the brain functional remodeling. The brain reintegration mechanism appears to be asymmetrical and the lateralization pattern in the contralateral brain hemisphere for auditory information processing related with the severity of hearing impairment. Key Words: Fractional amplitude of low frequency fluctuation; Hearing loss; Unilateral hearing impairment; Functional magnetic resonance imaging. © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
INTRODUCTION
T
he incidence of unilateral hearing impairment (UHI) increases with age and is characterized by asymmetric auditory afferents where auditory information is asymmetrically transmitted to the brain (1,2). Recognition and processing of auditory information are advanced functions in the human brain, implying that the underlying mechanisms of hearing impairments are complex (3,4). Hearing imbalance can cause poor sound localization and difficulty in
Acad Radiol 2019; &:1–8 From the Department of Imaging, Heping Hospital affiliated to Changzhi Medical College, Changzhi, PR China (J.Z., J.J.); Department of Imaging, Hepji Hospital affiliated to Changzhi Medical College, Changzhi, PR China (J.C.); Department of radiology, Peking University Lu’an Hospital, Changzhi, PR China (G.C., Y.L.); Graduate School of Changzhi Medical College, Changzhi, PR China (X.C.); Department of Imaging, Yuncheng Central Hospital, Yuncheng, PR China (C.Z.). Received August 11, 2019; revised September 13, 2019; accepted September 18, 2019. Address correspondence to: Y.L. e-mail: [email protected] 1 These authors contributed equally. © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.acra.2019.09.027
directional hearing, and long-term UHI can result in cerebral functional alterations and reorganization (5,6). Functional magnetic resonance imaging (fMRI) studies have been performed on patients with hearing impairments providing valuable insights into associated auditory information processing and functional integration mechanisms of the brain. Neurons encode binaural time or intensity signals by converting them into information about spatial characteristics in order to obtain the spatial location of sound. In addition, binaural information integration can also help to interact with brain function activity, which can maintain the relative acoustic stability in a certain background of stimulus parameters (7). The auditory cortex responsible for auditory function is located in the upper medial fissure of bilateral temporal lobe and includes the Heschl’s gyrus (HG) and part of the temporal gyrus (8). Studies have shown that patients with UHI exhibit psychological changes, which may result from functional activity changes in some brain regions including the right supramarginal gyrus, bilateral thalamus, and prefrontal lobe (9 11). Moreover, fMRI has shown that patients with UHI exhibit cortical functional remodeling of bilateral transverse temporal gyrus because of unilateral auditory
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stimulation and bilateral imbalance of auditory conduction (12,13). In such instances, the impaired side significantly affects the corresponding lateralization pattern and results in hemispheric dominance of auditory processing in the auditory functional network. While studies have begun to highlight functional changes in UHI, the exact association between unilateral auditory input patterns and auditory activity alterations of corresponding brain regions are still being explored (14 17). Amplitude of low frequency fluctuation (ALFF) can be calculated with the square root of power spectrum integrated in a low-frequency range (frequency range of 0 0.1 Hz) and it is an index used for detecting the regional intensity of spontaneous fluctuations in blood oxygen-level dependent signal of resting state functional MRI (18). Fractional ALFF (fALFF) is a methodological improvement of ALFF, denoted as the power within the low-frequency range divided by the total power in the entire frequency range (19). Both ALFF and fALFF reflect functional activities in the brain in the form of energy metabolism. Although previous neuroimaging studies have shown that certain brain regions related to auditory functions may be altered in patients with hearing impairments, fALFF studies on UHI are rare and the relationship between fALFF and the severity of hearing impairments remains unclear (20,21). Previous neuroimaging studies (22,23) also observed differences in abnormal brain activities in patients between left and right UHI. However, for patients with left or right long-term UHI, it is unclear whether there are bilateral fALFF differences along with abnormal functional activities. Therefore, we used fALFF to evaluate the functional alterations in patients with longterm UHI in order to identify the brain regions with abnormal functional activities in patients with left or right long-term UHI, respectively. In this study, we hypothesize that UHI leads to functional activity changes in certain regions of the brain and that intrinsic brain reintegration mechanisms will be different in patients with left- and right-sided hearing impairment. In addition, their altered brain functional activities correlate with the degree of hearing impairment. fALFF under resting-state fMRI was used to evaluate functional activities in the brains of healthy control and UHI patient groups. Differences in fALFF among the control group and patients with left or right UHI were compared and analyzed, respectively. Moreover, correlation analysis between quantitative fALFF, and the duration and severity of UHI was performed in the UHI group.
MATERIALS AND METHODS Participants
Thirty-three patients with UHI caused by idiopathic hearing loss were recruited for this study (20 male, 13 female, aged 24 55 years, mean age: 44.31 § 10.13), including 17 patients with left-sided hearing impairments and 16 patients with right-sided hearing impairments. All patients had been diagnosed with unilateral chronic hearing loss for at least 2 years. In addition, 32 healthy individuals (18 male, 14 2
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female, aged 22 58 years, mean age: 45.86 § 13.28) were recruited as the control group. Pure tone audiometry (PTA) was used to evaluate patients’ hearing level. Hearing thresholds of 500 kHz, 1000 kHz, 2000 kHz, and 4000 kHz were used to calculate the average PTA values in participants. All patients were diagnosed with moderate to severe impairments in one ear with PTA value of >40 dB HL, while all healthy ears and the control group had ''normal hearing'' at a PTA value of 25 dB HL. All participants were right-handed and patients with any of the following conditions were excluded: pregnancy, neurological diseases, poorly controlled hypertension, psychiatric disorders, history of heart disease, recent head injury, metabolic diseases, or any other condition that could affect the study. This study was approved by the hospital’s academic ethics committee and informed consent was obtained from all participants. Data Acquisition
A 3.0 T superconducting magnetic resonance scanner (MAGNETOM Skyra, German) with matched receiver coil and parallel imaging system was employed for MRI examination. All participants were asked to lie still, close their eyes, breathe calmly, and minimize head movements. Meanwhile, bilateral rubber earplugs and electrostatic headphones were given to reduce scanner noise and all participants were asked to refrain from sleeping and refrain from thinking about. First, localized images were obtained, following which conventional axial T2-weighted imaging was performed to exclude any organic lesions in the brain. Resting state fMRI was performed with an axial echo-planar imaging (GRE-EPI) sequence, using a single-shot acquisition technique (slice thickness = 3.5 mm, slice interval = 0.7 mm, repetition time (TR) = 2000 ms, echo time (TE) = 30 ms, inversion angle = 90°, matrix = 64 £ 64, field of view (FOV) = 240 £ 240 mm2, and number of excitations (NEX) = 1, 34 slices and 250 time points). Finally, a sagittal structural 3D T1-weighted image was collected using a 3D T1-weighted image with 3-dimensional fast spoiled gradientecho sequences (thickness =1 mm, TR = 6.7 ms, TE = min full, matrix = 256 £ 256, FOV = 256 £ 256 mm2, NEX = 1). Data Processing and Analysis
Data Preprocessing Data preprocessing was carried out using Data Processing Assistant for Resting-State fMRI (DPARSF, Advanced Edition). Preprocessing included data format conversion (from DICOM to NIFTI format), removal of the first five time points and slice-time correction. Head motion correction was carried out with a standard of 2 mm or 2°, and six motion parameters (three translation and three rotation) were obtained. Spatial standardization was performed. Functional images were coregistered with corresponding T1 structural images that were segmented and warped into the anatomical Montreal Neurological Institute template; they were then transformed at a resolution of 3-mm isotropic resolution into
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the standard Montreal Neurological Institute space. Spatial smoothing was performed with the full-width half-maximum was set to 4. Linear drift was removed and covariate regression was performed, and the white matter, cerebrospinal fluid signals, global signals, and six head-motion parameters were eliminated. Finally, Band-pass filtering was performed (0.01 0.08 Hz) to remove the effects of low-frequency drifts and high-frequency noise after fALFF calculation (24). fALFF Computation and Statistical Analysis fALFF values from resting state functional MRI were analyzed using Resting-State fMRI Data Analysis Toolkit v1.8 software (https://sourceforge.net/projects/resting-fmri). The time series of each voxel obtained from preprocessed data were converted to the frequency domain by a fast Fourier transform, and the square root of the power spectrum was computed as the ALFF. The ALFF value was then further divided by the global mean ALFF value to standardize the data within each group. The normalized ALFF value was divided by the ALFF value of the entire band to obtain the normalized fALFF value of each voxel. The differences between fALFF brain-maps from UHI and controls groups were compared using a two-sample t test, with covariance factors of sex, age, education level, and six head-movement parameters. Results were corrected using false discovery rate correction and p values were considered statistically significant at <0.05. The brain fALFF values at voxel level were extracted. These were used for Pearson’s correlations analysis with the PTA scores and the duration of hearing impairments, the differences were considered statistically significant if p < 0.05. RESULTS Clinical Data
There were no significant differences in sex, age, and educational level among UHI patient groups and healthy control groups (p > 0.05). The average duration and PTA of the affected ear in all patient groups were calculated (duration: mean 37.9 § 11.68 months and PTA: mean 67.4 § 18.75 dB HL in left-sided impairment; mean 36.88 § 10.29 months
and PTA: mean 68.5 § 21.22 dB HL in right-sided impairment). Moreover, the healthy side of patients, and both sides of the control group exhibited normal hearing ability (PTA 20 dB HL) (Table 1). fALFF Differences Between UHI Groups and Control Group
The left UHI group exhibited significantly higher fALFF values in the right HG, left inferior parietal lobule (IPL), right superior temporal gyrus (STG), left angular gyrus, right superior parietal gyrus (SPG), right precentral gyrus (PreCG), and right insula, compared with the control group. Furthermore, left UHI patients had significantly lower fALFF values in the right supplementary motor area (SMA) compared with the control groups (Table 2, Figure 1). The right UHI group exhibited significantly higher fALFF values in the left superior frontal gyrus, left HG, bilateral STG, bilateral middle frontal gyrus (MFG), right postcentral gyrus (postCG), left triangular part of inferior frontal gyrus (IFGtri), and left insula, compared with the control group (Table 3, Fig 2). Correlations Between Abnormal fALFF and PTA and UHI Duration
No significant correlation was found between fALFF values and duration of UHI. However, in the left UHI group, fALFF values positively correlated with PTA in the right HG (p< 0.01, r = 0.71) and right STG (p< 0.01, r = 0.74). Moreover, fALFF values negatively correlated with the PTA in the right insula (p< 0.01, r = 0.68) (Table 4, Fig 3). In the right UHI group, fALFF values positively correlated with PTA in the left HG (p < 0.01, r = 0.72) and left middle frontal gyrus (p < 0.01, r = 0.63). Moreover, fALFF values were negatively correlated with the PTA in the left insula (p< 0.05, p= 0.57) (Table 4, Fig 3). DISCUSSION In this study, fALFF values were used to evaluate resting-state changes in the functional activity of the brain in patients with
TABLE 1. Demographic and Clinical Data of Unilateral Hearing Impairment Patients and Healthy Controls All Patients (33) Protocols
Left Side(17)
Right Side(16)
HCs (32)
p Value
Gender (M/F) Age (y) Education (y) Duration (mo) PTA of affected ear (dB HL) PTA of normal ear (dB HL)
10/7 45.27 § 11.05 11.15 § 2.47 37. 9 § 11. 68 67.4 § 18.75 25
9/7 43.19 § 9.82 9.83 § 1.67 36. 88 § 10. 29 68.5 § 21.22 25
18/14 45.86 § 13.28 11.76 § 3.18 / / 25
0.34a 0.125b 0.238b 0.357c 0.326c /
HCs, healthy control patients; PTA pure tone audiometry. p Value was obtained using a Pearson chi-square test (two-tailed) among three groups. b p Value was obtained using one-way analysis of variance among three groups. c p Value was obtained using independent two samples t test between two groups. a
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TABLE 2. Brain Regions Showing Intergroup fALFF Differences Between Left Hearing Impairment and Healthy Control Groups
Brain Regions
BA
Peak MNI Coordinates (mm) (x, y, z)
HG.R IPL.L STG.R AG.L SPG.R PreCG.R SMA.R Insula.R
48 7 21 39 40 4 6 48
(52, 11, 7) ( 32, 57, 46) (59, 0, 10) ( 42, 65, 35) (42, 45, 60) (52, 8, 45) (7, 4,52) (42,4, 1)
t Value 2.72 3.48 2.55 2.43 2.88 3.36 3.53 3.26
AG.L, left angular gyrus; BA, Brodmann area; HG.R, right Heschl’s gyrus; Insula.R, right insula; MNI, Montreal Neurologic Institute; PL. L, inferior parietal lobule; PreCG.R, right precentral gyrus; SMA.R, right supplementary motor area; SPG.R, right superior parietal gyrus; ISTG.R, right superior temporal gyrus.
chronic UHI. fALFF is a relative ratio which is related to the total value and fluctuation amplitude value (18). At present, there is no study to measure the normal value level in large scalar group. In a small sample study the intergroup differences and statistical differences depend on the extent of differences between patients and healthy subjects (19). Previous study by Schmithorst et al. (25) showed that cortical remodeling occurs in patients with UHI for at least 2 years. Hence, this study included patients with a history of hearing impairment for at least 2 years. Significantly higher fALFF values were observed in the HG, STG, and insula in the UHI groups when compared with the control group. HG, also called the transverse temporal gyrus, is the primary cortical structure that processes auditory inputs and is shown to be active during tone and semantic tasks using fMRI (26). HG has been found to have significantly faster processing rates (33 Hz) in the left hemisphere than in the right hemisphere (3 Hz) (27). Additionally, the difference in processing rates was found to correlate with the volume of rate-related cortex in the HG, while the right HG is shown to be more active during auditory information processing than the left HG (28). The STG, in addition to its function in language processing, is an essential structure in auditory processing, and is involved
TABLE 3. Brain Regions Showing Intergroup fALFF Differences Between Right Hearing Impairment and Healthy Control Groups
Brain Regions
BA
Peak MNI Coordinates (mm) (x, y, z)
SFG.L HG.L STG.L STG.R MFG.L MFG.R PostCG.R IFGtri.L Insula.L
46 48 21 21 46 48 3 45 48
( 25, 53, 24) ( 48, 13, 7) ( 54, 0, 11) (57, 0, 6) ( 27, 37, 29) (29, 32, 19) (52,-19,40) ( 44,32,20) ( 40,1, 1)
t Value 2.66 3.27 2.47 2.35 2.74 2.83 3.45 2.64 3.15
BA, Brodmann area; HG.L, left Heschl’s gyrus; IFGtri.L, left triangular part of inferior frontal gyrus; Insula.L, left insula; MFG.L, left middle frontal gyrus; MFG.R, right middle frontal gyrus; MNI, Montreal Neurologic Institute; PostCG.R, right postcentral gyrus; SFG.L, left superior frontal gyrus; STG.L, left superior temporal gyrus; STG.R, right superior temporal gyrus.
in the processing of auditory information related to facial expressions (29). Moreover, research conducted with fMRI showed a link between insight-based problem solving and brain activity, specifically related to sudden auditory information (30). The STG is also involved in the perception of emotions in facial stimuli (31,32). The insula is involved in multimodal sensory processing, and functional imaging studies (33,34) have shown the activation of the insula during audio-visual integration tasks, indicating that the insula may be involved in the interactive remodeling of the auditory and visual functional network. Interestingly, in this study, some brain regions exhibited functional changes only in the one-sided impairment group. Abnormal fALFF values were observed in the IPL, angular gyrus, SPG, SMA, and PreCG only in the left-sided group. The SPG is involved in spatial orientation, receiving enormous amounts of visual and sensory input (35). While the IPL and angular gyrus are related to the perception of facial emotions as well as language comprehension and production (35). Furthermore, the PreCG and SMA are related to the prominent gyrus in the somatic motor cortex, usually described as the main and supplementary
Figure 1. Brain regions showed fALFF differences between left hearing impairment and healthy control groups. The abnormal regions with higher fALFF were observed in the right Heschl’s gyrus (HG), left inferior parietal lobule (IPL), right superior temporal gyrus (STG), left angular gyrus (AG), right superior parietal gyrus (SPG), right precentral gyrus (PreCG), and right insula. The regions with lower fALFF were observed in the right supplementary motor area (SMA) as compared with healthy controls.
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Figure 2. Brain regions showed fALFF differences between right hearing impairment and healthy control groups. The abnormal regions with higher fALFF were observed in the left superior frontal gyrus (SFG), left Heschl’s gyrus, bilateral superior temporal gyrus, bilateral middle frontal gyrus (MFG), right postcentral gyrus (postCG), left triangular part of inferior frontal gyrus (IFGtri), and left insula.
area for motion (36). SMA is the only brain region related to motor function and was found to be negatively active in our study. The SMA exists in an overlapping somatotopic arrangement, found on the contralateral side of the brain to the corresponding body parts. As a result, in patients with UHI, functional activity of SMA was relatively lower on the contralateral side to impaired hearing than the ipsilateral side. Previous studies have suggested that perceptual compensation allows individuals to obtain sufficient information about the environment, by perceiving stimuli that are suitable for their own sensory patterns (24). For example, a study using magnetoencephalography found that visual areas in blind individuals are used to perform auditory functions (37). Therefore, the altered activity of these nonauditory areas in patients with UHI may support the perceptual compensation theory (38,39). Abnormal fALFF values were observed in the superior frontal gyrus, middle frontal gyrus, postcentral gyrus, and triangular part of inferior frontal gyrus only in the right-sided group. Among these regions, the frontal cortex is extremely important for language comprehension and production, and it has also been shown to play a role in inhibitory processes, including inhibiting learning of undesirable information (40). Furthermore, the postcentral gyrus is a prominent gyrus in the primary somatosensory cortex, usually described as the main sensory receptive area for touch (41,42). Comparison of auditory and visual processing showed that extensive brain areas were activated in both the parietal lobes and the inferior frontal gyrus, when integrating auditory and visual information. The abnormal functional activity of these brain areas in the present study suggests that brain reorganization mechanisms may occur in UHI patients with neurological deafness (43). However, the findings of this study are not entirely
consistent with previous literature. In previous studies, altered functional activities were found in the supramarginal gyrus of patients with hearing impairments (44 47). However, in this study, no significant differences were found in the supramarginal gyrus between UHI patients and the control groups (24). Furthermore, a previous study (34) showed that patients with rightsided hearing impairment showed abnormal fALFF alteration in the precuneus, and middle and inferior temporal gyrus, which showed no significant differences in our study. Previous studies inferred that the brain’s functional network may undergo neuroplastic changes during different physiological conditions, to adapt to the needs of the surrounding environment (23). Moreover, our results indicate that reorganization mechanisms are further complicated by the integration of different brain functional activities besides auditory function in the brain of UHI patients. On the other hand, abnormal fALFF values and the duration of UHI showed no significant correlations, indicating that the stages of the disease, shown in this study, do not affect brain function remodeling. However, both sides of HG, the right STG, and the left middle frontal gyrus showed positive correlations with PTA values in the impairment groups. These results highlight the role of HG, the STG, and the middle frontal gyrus in processing auditory inputs (48) and suggest that the relative activity of auditory functions in the left and right hemispheres are related to the severity of UHI. In contrast, regions showing negative correlations with PTA, were the bilateral insulae. The insular cortex is involved in multimodal sensory processing (33). Functional imaging studies show that the insular lobe is activated in audiovisual integration tasks and insular lobe is therefore involved in the interactive remodeling of
TABLE 4. Brain Regions Showed Correlation with PTA in Hearing Impairment Groups Group
Brain Regions
Correlation with
Left hearing impairment
HG.R STG.R Insula.R HG.L MFG.L Insula.L
PTA PTA PTA PTA PTA PTA
Right hearing impairment
r Values 0.71 0.74 0.68 0.72 0.63 0.57
p Values 0.001 0.001 0.002 0.001 0.009 0.02
HG.R, right Heschl’s gyrus; Insula.L left insula; Insula.R, right insula; MFG.L, left middle frontal gyrus; STG.R, right superior temporal gyrus.
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Figure 3. Correlations between altered fALFF values (vertical axis) of brain regions and corresponding PTA scores (transverse axis) of the patients. (A) The fALFF values that positively correlated with the PTA were the right Heschl’s gyrus (HG) and superior temporal gyrus (STG), and negatively correlated with the PTA were the right insula in the patients with left hearing impairment. (B) The fALFF values that positively correlated with the PTA were the left Heschl’s gyrus (HG) and middle frontal gyrus (MFG), and negatively correlated with the PTA were the left insula in the patients with right hearing impairment.
auditory and visual functional networks (34). We can speculate that auditory processing is related to information transmission to the contralateral hemisphere and that a decrease in auditory activity indicates a higher severity of UHI. These results correspond with those from previous studies (49) showing that the contralateral hemisphere exhibits brain lateralization for processing auditory information. This study has limitations. First, the sample size was relatively small and therefore the validity of statistical inference is low. Second, although, earplugs and electrostatic headphones were given to participants during fMRI scanning, the noise of the MRI scanner could not be completely eliminated. Finally, patients with UHI were not segregated based on etiology. Therefore, to verify the reliability of the results, in the future we should have to increase the sample size, use etiological grouping to differentiate between causes of the disorder, and apply methods to eliminate the impact of MRI noise.
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CONCLUSION This study provides significant evidence for altered resting-state functional activities in the brain of patients with left or right long-term UHI. Significantly increased fALFF values were observed in the HG, STG, and insula in both left- and rightsided UHI groups. Moreover, some brain regions exhibited functional changes only in the one-sided impairment group. Complicated network reorganization was seen in regions of the brain involved visual, cognitive, sensorimotor and information transmission functions besides the auditory function in the UHI patients. In addition, it is the severity of hearing impairment and not the duration of UHI which is associated with functional activity in different brain regions. In conclusion, multiple brain regions within different functional networks were involved in the brain functional remodeling for UHI patients. The altered functional activities in certain brain regions are not symmetrical and the lateralization pattern in
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fALFF ALTERATIONS IN UNILATERAL HEARING IMPAIRMENTS
the contralateral brain hemisphere for auditory information processing is related to the severity of hearing impairment.
AUTHOR CONTRIBUTIONS Jiangping Zhu and Jiangbo Cui contributed equally, they acquired and analyzed data, drafted the manuscript, and revised it. Gang Cao, Xu Chang, Jianwu Ji, and Chongjie Zhang analyzed and explained the data, and checked the data. Yongbo Liu revised the manuscript for extremely important intellectual content.
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