
==== Front
BMC Neurol
BMC Neurol
BMC Neurology
1471-2377
BioMed Central London

3819
10.1186/s12883-024-03819-5
Research
A comparative study of vestibular projection connectivity and balance in healthy young adults and elderly subjects
Yeo Sang Seok 1
Oh Seunghue 2
Cho In Hee choinhee95@hanmail.net

3
1 https://ror.org/058pdbn81 grid.411982.7 0000 0001 0705 4288 Department of Physical Therapy, College of Health Sciences, Dankook University, Dongnam-gu, Cheonan-si, Chungnam, Republic of Korea
2 https://ror.org/01jt32312 grid.443812.8 0000 0000 9565 9836 Department of Physical Therapy, Uiduk University, Gyeongju-si, Republic of Korea
3 https://ror.org/058pdbn81 grid.411982.7 0000 0001 0705 4288 Department of Health, Graduate School, Dankook University, 119, Dandae-ro, Dongnam-gu, 31116 Cheonan-si, Chungnam, Republic of Korea
6 9 2024
6 9 2024
2024
24 3242 4 2024
22 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Objective

Vestibular function is controlled by interactions between various neuropathways that have different effects on balance and are connected to various brain areas. However, few studies have investigated the relation between changes in VN connectivity and aging using neuroimaging. We investigated neural connectivities in the vestibular nucleus (VN) and ventralis intermedius (VIM) nucleus of the thalamus in young and old healthy adults by diffusion tensor imaging.

Methods

This study recruited twenty-three normal healthy adults with no history of a neurological or musculoskeletal disease, that is, eleven old healthy adults (6 males, 5 females; mean age 63.36 ± 4.25 years) and 12 young healthy adults (7 males, 5 females; mean age 28.42 ± 4.40 years). Connectivity was defined as the incidence of connection between the VN, VIM, and target brain regions. Incidence of connection was counted from VN and VIM to each brain region. The subjective visual vertical (SVV) and the Berg balance scale (BBS) were used to assess vestibular function and balance.

Results

The VN showed high connectivity with brainstem (dentate nucleus, medial longitudinal fasciculus, and VIM), but relatively low connectivity with cerebral cortex (parieto-insular vestibular cortex (PIVC) and primary somatosensory cortex) at a threshold of 30 streamlines. In particular, VN connectivity with PIVC was significantly lower in elderly adults (> 60 years old) than in young adults (20–40 years old) (p < 0.05). VIM showed high to mid connectivity with brainstems and cerebral cortexes at a threshold of 30, but no significant difference was observed between young and old adults (p > 0.05). SVV and BBS showed no significant differences between young and old adults (p > 0.05).

Conclusion

We investigated incidences of neural connectivities of VN and VIM in young and old healthy adults. Our results provide basic data that might be clinically useful following injury of vestibular-related areas.

Keywords

Vestibular nucleus
Ventralis intermedius
Connectivity
Diffusion tensor imaging
Aging
http://dx.doi.org/10.13039/501100003725 National Research Foundation of Korea RS-2022-00165732 issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
==== Body
pmcIntroduction

Balance control is required to maintain the center of mass within the support base and is an important consideration for ambulation and reducing fall risk [1, 2]. Balance ability requires the complex integration of visual, vestibular, and somatosensory systems [1, 3], but age-related degenerative changes in the neuromuscular system adversely affect balance ability, and thus, fall risk [1, 2, 4]. Previous studies have suggested age-related reductions in balance ability are caused by diminished abilities of the musculoskeletal, visual, somatosensory, and vestibular systems [1, 2]. In particular, some studies have investigated the effect of age on the relation between the vestibular system and balance ability [5, 6]. The vestibular system plays an important role in controlling head, body, and eye movements [7, 8]. However, unlike other sensory systems, previous studies have suggested that it has limitations to easily measure changes in vestibular functions because the assessment techniques are not various and not easily applicable [3, 6, 7, 9]. Furthermore, the need for sensitive measurement techniques that are capable of allowing evaluation of central and peripheral vestibular functions has increased in parallel with societal aging [10, 11]. Recent studies have demonstrated relations between vestibular functions and aging using the subjective visual vertical (SVV), which is a sensitive, simple neurophysiological technique, and have reported vestibular function diminishes with age [12–14].

Especially, vestibular function is mainly controlled by central neural system that interactes between various brain areas and neuropathways [15, 16], the latter of which may have different effects on balance depending on the brain areas and volume they project [15–17]. Many authors have suggested that vestibular projection pathways mainly connect with the parieto-insular vestibular cortex (PIVC), ventralis intermedius (VIM) nucleus of the thalamus, medial longitudinal fasciculus (MLF), vestibular nucleus (VN), and dentate nucleus (DN) of cerebellum [13, 18–21]. Previous studies have reported that the PIVC in the posterior parietal operculum/retroinsular region is a core region of vestibular input [22–24]. The PIVC contributes to the processing of bodily self-consciousness, estimation of verticality, and to the integration of visual motion [23, 25]. The VIM nucleus is located laterally to the thalamus between the ventral posteromedial nucleus and ventral lateral nucleus, whereas the MLF is situated in the medial part of the ipsilateral midbrain [17, 26], and the VIM and MLF play important roles in the sensing of body rotation and head tilt [17, 26]. Several authors have suggested correlations exist between the VIM and MLF and vestibular function based on visual vertical data, and have reported VIM and MLF receive vestibular signals related to visual vertical from the VN [9, 17, 27]. The DN of cerebellum is a main contributor to vestibular function because it receives vestibular input through projection pathways. In particular, the DN receives vestibular information from the VN and outputs information processed in the DN of cerebellum [28, 29]. Some researchers have emphasized a relation between the VN in brainstem and vestibular function because most vestibular inputs related to the PIVC, VIM, MLF, and cerebellum pass through the VN [9, 23, 27, 30]. In 2014, Conrad et al. reviewed the role and function of vestibular structures in the central vestibular system, and reported vestibular projection pathways ascended through the superior VN and that vestibular input was transmitted from the VN to other vestibular structures(9).

Diffusion tensor imaging (DTI) enables functional connectivity and anatomical structures to be visualized and reconstructed by imaging water diffusion patterns [31–33]. DTI provides images of the diffusion properties of white matter by quantifying diffusion in multiple directions [31–33]. Previous studies have reconstructed human neural connectivity in the VN and in other brain areas in three dimensions [23, 24, 28], and other studies have reported age-related changes in DTI parameters [34–36]. However, few studies have investigated the relation between changes in VN connectivity and aging.

In the present study, we reconstructed neural connectivity in the vestibular and ventralis intermedius nuclei of thalamus by DTI and investigated the association between neural connectivity and balance ability related to visual vertical in young and old healthy adults.

Materials and methods

Subjects

Twenty-three normal healthy adults with no history of a neurological or musculoskeletal disease were recruited for this study, that is, eleven old healthy adults (6 males, 5 females; mean age 63.36 ± 4.25 years) and 12 young healthy adults (7 males, 5 females; mean age 28.42 ± 4.40 years). Inclusion criteria for this study were as follows: (1) participants who had previously not been diagnosed with the musculoskeletal, neurologic and cognitive problems; (2) participants who were not diagnosed with problems related to brain injury by doctors. All participants provided informed consent prior for DTI and balance ability assessments. The study protocol was approved by the institutional review board of Yeungnam University Hospital (YUMC 2019-04-050-001).

Diffusion tensor image and probabilistic fiber tracking

The DTI data were acquired using a sensitivity-encoding head coil on a 1.5 T Philips Gyro scan Intera (Philips, Best, The Netherlands) with single-shot echo-planar imaging. For each of the 32 non-collinear diffusion sensitizing gradients, 67 contiguous slices (acquisition matrix = 96 × 96; reconstructed matrix = 192 × 192; field of view = 240 × 240 mm2; TR = 10,726 ms; TE = 76 ms; b = 1000 s/mm2; NEX = 1; and a slice thickness of 2.5 mm) were collected parallel to the anterior commissure-posterior commissure line [22].DTI data was analyzed using the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL; www.fmrib.ox.ac.uk/fsl). Head motion effect and image distortion due to eddy currents were corrected for using affine multi-scale two-dimensional registration. Fiber tracking was performed using a probabilistic routines based on a multifiber model in FMRIB Diffusion (5000 streamline samples, 0.5 mm step length, curvature threshold = 0.2) [37]. To reconstruct VN connectivity, a seed ROI was placed on the VN at the level of the pons equivalent to Deiters’ nucleus and Schwalbe’s nucleus (Fig. 1) [38]. VIM connectivity was reconstructed by placing a seed ROI between the ventral caudalis and the ventral oralis (anterior and posterior) nucleus at the level of the ventral thalamus (Fig. 2) [39]. 5000 samples were generated from the seed voxel, and results were visualized at a threshold of 1, 10 and 30 streamlines through each voxel for analysis.

Fig. 1 (A) Seed ROI used to determine connectivity of the VN (Deiters’ nucleus and Schwalbe’s nucleus) at the pons level. (B) Results of neural connectivity between the VN and vestibular-related areas (S1, PIVC, VIM nucleus of the thalamus, MLF, and DN of the cerebellum) in young and old healthy adults. (C) The structural connectivity of the VN at 1, 10, 20 and 30 streamlines as determined by DTI

Fig. 2 (A) Seed ROI for connectivity of the VIM nucleus of the thalamus was placed between the ventral anterior and posterior nucleus at the ventral thalamus level. (B) Results of neural connectivity between the VIM nucleus of the thalamus and vestibular-related areas (S1, PIVC, MLF, VN and DN of cerebellum) in young and old healthy adults. (C) The structural connectivity of the VIM thalamus at thresholds of 1, 10, 20 and 30 streamlines as determined by DTI

Determination of connections between the VN, VIM nucleus of the thalamus and target brain regions

Connectivity was respectively defined as the incidence of connection between the VN, VIM and the following target brain regions and calculated by whether the results passed through each target brain regions: (1) primary somatosensory cortex (S1), PIVC, VIM nucleus of the thalamus, MLF and DN of cerebellum, and (2) S1, PIVC, MLF, VN, and DN of cerebellum. Incidence of connection was counted from the VN and VIM nucleus to each brain region.

Functional evaluation

Subjective visual vertical (SVV)

Subjective visual vertical (SVV) was assessed using an opaque plastic bucket. A vertical straight line was placed on the interior bottom of the cylindrical bucket using color tape [40]. A protractor was then attached on the exterior bottom of the bucket so that the interior vertical straight line and protractor’s zero line were aligned [40]. A pendulum was positioned on the exterior bottom so as to match the zero line of the protractor [40]. The participants received the bucket after random rotation and were instructed to look at the line inside the bucket and to turn the buck so that the line was disposed vertically in a sitting position [40]. We measured angular deviations from true vertical regardless of whether they were clockwise or counter clockwise. SVV testing was performed in a subdued light to avoid a reflection from the protractor. The SVV test was performed three times and results were averaged.

Berg balance scale (BBS)

The Berg balance scale (BBS) was developed to evaluate balance in old adults [41]. The scale is composed of 14 items that address activities of daily living such as standing, moving, and turning. Items were each scored from 0 to 4, and thus, possible total scores varied from 0 to 56, where higher scores represented better balance. The BBS was conducted three times and results were averaged.

Statistical analysis

SPSS ver. 20.0 (SPSS, Inc., Chicago, Illinois) was used to analyze results. The chi-square test was used to determine the significances of differences in the incidences of connectivity in the VN and VIM nucleus of the thalamus in young and old adults. Differences of SVV and BBS between young and old adults were analyzed using Mann-Whitney U-test. Statistical significance was accepted for p values < 0.05.

Results

Structural connectivities of the VN and VIM

Connectivity of the VN

Reconstruction of VN connectivity is shown in Table 1; Fig. 1. VN showed 100% connectivity with the DN in the young and old groups regardless of the streamline threshold used. At thresholds of 1, 10, or 30, connectivity with the PIVC steadily decreased in young (100%, 95.83% and 79.17%, respectively) and old adults (100%, 86.36% and 50%, respectively). Notably, at a threshold of 30, connectivity with the PIVC was significantly lower in old (50%) than in young adults (79.17%) (p < 0.05). Connectivities with S1, VIM nucleus, and MLF, but not connectivities with the PIVC also showed decrements with increasing threshold in young and old adults, but connectivities at each threshold were not significantly different in the two groups (p > 0.05) (Table 1).

Table 1 Comparison of incidence of connectivity (%) from VN to target brain regions between young and old healthy adults

	Threshold (streamline)	
1		10		30	
Target brain region	Young	Old	p	Young	Old	p	Young	Old	p	
S1	95.83	100.00	0.333		79.17	90.91	0.268		62.50	63.64	0.936	
PIVC	100.00	100.00	1.000		95.83	86.36	0.255		79.17	50.00	0.038*	
VIM	100.00	100.00	1.000		100.00	95.45	0.291		91.67	90.91	0.927	
MLF	100.00	100.00	1.000		100.00	100.00	1.000		95.83	100.00	0.333	
DN	100.00	100.00	1.000		100.00	100.00	1.000		100.00	100.00	1.000	
VN: vestibular nucleus; S1: primary somatosensory cortex; PIVC: parieto-insular vestibular cortex; VIM: ventralis intermedius; MLF: medial longitudinal fasciculus; DN: dentate nucleus

* p < 0.05

Connectivity of the VIM nucleus of the thalamus

VIM connectivities are summarized in Table 2; Fig. 2. VIM showed 100% connectivity with target brain regions (S1, MLF and VN) in old adults regardless of threshold. In contrast, young adults showed lower connectivities with S1 (95.83%), MLF (95.83%) and VN (95.83%) at a threshold of 30. However, no significant difference was observed between the VIM connectivities of young and old adults (p > 0.05). At thresholds of 1, 10, and 30 streamlines, VIM connectivities with PIVC and DN of cerebellum steadily reduced in young and old adults, but no significant difference was observed between young and old adults (p > 0.05) (Table 2).

Table 2 Comparison of incidence of connectivity (%) from VIM nucleus on thalamus to target brain regions between young and old healthy adults

	Threshold (streamline)	
1		10		30	
Target brain region	Young	Old	p	Young	Old	p	Young	Old	p	
S1	100.00	100.00	1.000		100.00	100.00	1.000		95.83	100.00	0.333	
PIVC	100.00	100.00	1.000		100.00	95.45	0.291		87.50	72.73	0.207	
MLF	100.00	100.00	1.000		100.00	100.00	1.000		95.83	100.00	0.333	
VN	100.00	100.00	1.000		95.83	100.00	0.333		95.83	100.00	0.333	
DN	100.00	95.45	0.291		95.83	95.45	0.950		91.67	86.36	0.564	
VIM: ventralis intermedius; S1: primary somatosensory cortex; PIVC: parieto-insular vestibular cortex; MLF: medial longitudinal fasciculus; VN: vestibular nucleus; DN: dentate nucleus

* p < 0.05

Functional evaluation

SVV scores of the two groups were not significantly different, though the SVV scores of young adults tended to be lower (p > 0.05) (Table 3). Furthermore, although mean BBS scores also tended to be lower for old adults, there was no significant difference between young and old adults (p > 0.05) (Table 3).

Table 3 Comparison of the results of SVV and BBS between young and old healthy adults

	SVV (deg)	BBS (score)	
Young	1.75

(1.08)

	56.00

(0.00)

	
Old	2.68

(1.65)

	55.91

(0.30)

	
p	0.152	0.296	
Values represent mean (± standard deviation)

SVV: subjective visual vertical; BBS: Berg balance scale

* p < 0.05

Discussion

We investigated differences between the vestibular connectivities of the VN and VIM in young and old adults using probabilistic DTI tractography. We found high connectivity between the VN and vestibular-related areas in the diencephalon and which were commonly affected by brain stem lesion (DN:100%, MLF: 97.8%, VIM: 91.3% at a threshold of 30 streamlines), but a relatively low level of connectivity with cerebral cortex (PIVC: 65.2% S1: 63.0% at 30 streamlines). Notably, VN connectivity with the PIVC was significantly lower in old adults. The VIM vestibular connectivity showed high to mid connectivity with the brain stem (VN: 97.8%, MLF: 97.8%, DN: 89.1% at a threshold 30) and cerebral cortex (S1: 97.8%, PIVC: 80.4% at a threshold 30). However, VIM connectivities to vestibular-related areas were non-significantly different in young and old adults. Summarizing, no significant age-related relations between VN and VIM connectivities to vestibular related areas was observed, with the exception of the PIVC. These results suggest no significant differences in balance or visual vertical functions between young and old adults. On the other hand, diminished VN connectivity to the PIVC observed in old adults might be associated with aging with the vestibular system.

The PIVC processes and integrates vestibular information and makes allowances for gravity when body and head positions change, and is known to receive vestibular information from the vestibular nucleus through the VIM of the ventrolateral thalamus [42, 43]. Postural vertical and visual vertical adjustment based on gravitational information are the most important roles of the PIVC and thalamic nucleus associated with vestibular function [9, 24, 44, 45]. In terms of visual vertical testing, SVV tilt is commonly caused by bilateral vestibular dysfunction or a unilateral lesion of the labyrinth, vertical semicircular canal, or vestibular related nucleus [27, 42, 46]. According to previous study, SVV deviation caused by a peripheral lesion increased under condition where the visual background was rotated unlike in static visual background condition [42]. It was suggested that visual vertical was not controlled solely by vestibular system but by interplay between the vestibular and somatosensory systems [42]. Likewise, previous studies regarding SVV tilt caused by a central lesion reported on pathologic SVV tilt in patients with brain injury such as posterolateral, paramedian infarction and medial temporal gyrus hemorrhage [47, 48]. These results suggested vestibular function may be connected to various cortical areas around the core vestibular cortex as the PIVC [47, 48]. In other words, maintaining visual vertical to gravity or postural change is probably controlled by complex interactions between various brain regions and systems such as the vestibular, visual, and somatosensory systems, rather than a single nervous system or brain region.

In terms of vestibular projection pathways, several studies have recently used neuroimaging techniques to investigate the functional and structural connectivities of vestibular related areas [24, 49, 50]. According to the previous studies, the VIM and the ventralis oralis posterior (VOP) of the thalamic nucleus have different connectivities with brain regions with regard to motor thalamus. Especially, VIM showed greater connectivity to the ipsilateral M1 and the contralateral cerebellum than the VOP [49]. As regards the VN, it has been reported functional and structural connectivities with vestibular-related regions, that is, with the thalamic nucleus, PIVC, and VN [24]. In details, the left VN was functionally connected with the contralateral VN, both piriform cortexes, both insular cortexes, and the contralateral perirhinal cortex [24], and the right VN showed functional connectivities with the contralateral VN, both insular cortexes, and the ipsilateral posterior entorhinal cortex [24]. In addition, a recent study showed that VN to the vestibular related region was 100% connected with cerebellum, thalamus, oculomotor nucleus, trochlear nucleus, abducens nucleus, and reticular formation [50]. In contrast, VN connectivity to the premotor cortex, posterior parietal cortex, and prefrontal cortex showed relatively low connectivity (< 50% at a threshold of 15) [50]. These results of previous studies are consistent with high connectivities of VN and VIM to brainstem and the cerebral region and relatively low connectivities to the cerebral cortex.

Although no significant age-related association was found between neural connectivity and balance ability, our results indicate an age-related association between connectivities of the VN and VIM and the PIVC related to vestibular according to aging and provide basic data that might be clinically useful in cases involving injury to vestibular-related areas. According to previous study, the vestibular neural pathway projecting from vestibular nucleus to PIVC was decreased as age was increased [51] It is consistent with the results of this study, which showed that the connectivity between the VN and PIVC was significantly decreased with age. Another study reported that the vestibular nucleus was connected to various brain areas such as cerebellum, thalamus and posterior insular cortex and the changes of these vestibular projections were affected by age [52]. In other words. these suggested that vestibular function may be decreased because connectivity between vestibular-related areas is decreased according to aging. However, some of the results of this study are inconsistent with the results of previous studies, and the reasons for this are as follows: First, generalizations of our findings are difficult because of the small numbers of subjects recruited and we suggest that future study need to recruit the participants as conducting G*Power sample size calculations. Second, we only evaluated the balance ability using BBS and vestibular function using SVV. It is necessary to evaluate the balance ability using various assessment techniques such as mini-balance evaluation systems test and the vestibular function is needed to assess using VEMP and VOR. Third, we could not sufficiently rule out the effects of changes in visual function and somatosensory system on balance and visual vertical function due to aging. Finally, it was difficulty to locate ROIs accurately because of the diminutive size of the VIM nucleus and we only considered connectivity of the ipsilateral projection. Therefore, we suggest future research be conducted to investigate the association between neural connectivity and vestibular-related areas in contralateral projection.

Author contributions

All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization: S.S.Y. Methodology: S.S.Y. and I.H.C. Investigation: .S.H.O. and I.H.C. Formal Analysis: I.H.C. Writing - Original Draft: S.S.Y. and I.H.C. Writing - Review & Editing: S.S.Y. Visualization: S.H.O. and I.H.C.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. RS-2022-00165732).

Data availability

The raw data supporting the conclusions of this manuscript will be made available on request to the corresponding author.

Declarations

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the Medical Ethics Committee of Yeungnam University Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants provided informed consent prior for DTI and balance ability assessments. The study protocol was approved by the institutional review board of Yeungnam University Hospital (YUMC 2019-04-050-001).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

SVV Subjective visual vertical

PIVC Parieto-insular vestibular cortex

VIM Ventralis intermedius

MLF Medial longitudinal fasciculus

VN Vestibular nucleus

DN Dentate nucleus

DTI Diffusion tensor imaging

S1 Primary somatosensory cortex

VOP Ventralis oralis posterior

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Osoba MY Rao AK Agrawal SK Lalwani AK Balance and gait in the elderly: a contemporary review Laryngoscope Invest Otolaryngol 2019 4 1 143 53 10.1002/lio2.252
Osoba MY, Rao AK, Agrawal SK, Lalwani AK. Balance and gait in the elderly: a contemporary review. Laryngoscope Invest Otolaryngol. 2019;4(1):143–53.10.1002/lio2.252
2. Dunsky A Zeev A Netz Y Balance performance is Task Specific in older adults Biomed Res Int 2017 2017 7 10.1155/2017/6987017
Dunsky A, Zeev A, Netz Y. Balance performance is Task Specific in older adults. Biomed Res Int. 2017;2017:7.10.1155/2017/6987017
3. Cronin T Arshad Q Seemungal BM Vestibular deficits in neurodegenerative disorders: Balance, Dizziness, and spatial disorientation Front Neurol 2017 8 538 10.3389/fneur.2017.00538 29123498
Cronin T, Arshad Q, Seemungal BM. Vestibular deficits in neurodegenerative disorders: Balance, Dizziness, and spatial disorientation. Front Neurol. 2017;8:538.29123498 10.3389/fneur.2017.00538
4. Salzman B Gait and balance disorders in older adults Am Fam Physician 2010 82 1 61 8 20590073
Salzman B. Gait and balance disorders in older adults. Am Fam Physician. 2010;82(1):61–8.20590073
5. Jahn K The aging vestibular system: dizziness and imbalance in the Elderly Adv Otorhinolaryngol 2019 82 143 9 30947233
Jahn K. The aging vestibular system: dizziness and imbalance in the Elderly. Adv Otorhinolaryngol. 2019;82:143–9.30947233
6. de Melker Worms JLA Stins JF Beek PJ Loram ID The effect of fear of falling on vestibular feedback control of balance Physiol Rep 2017 5 18 27 10.14814/phy2.13391
de Melker Worms JLA, Stins JF, Beek PJ, Loram ID. The effect of fear of falling on vestibular feedback control of balance. Physiol Rep. 2017;5(18):27.10.14814/phy2.13391
7. Zalewski CK Aging of the human vestibular system Semin Hear 2015 36 3 175 96 10.1055/s-0035-1555120 27516717
Zalewski CK. Aging of the human vestibular system. Semin Hear. 2015;36(3):175–96.27516717 10.1055/s-0035-1555120
8. Miles RD Zapala DA Vestibular function Measurement devices Semin Hear 2015 36 1 49 74 10.1055/s-0034-1396926 27516710
Miles RD, Zapala DA. Vestibular function Measurement devices. Semin Hear. 2015;36(1):49–74.27516710 10.1055/s-0034-1396926
9. Conrad J Baier B Dieterich M The role of the thalamus in the human subcortical vestibular system J Vestib Research: Equilib Orientat 2014 24 5–6 375 85 10.3233/VES-140534
Conrad J, Baier B, Dieterich M. The role of the thalamus in the human subcortical vestibular system. J Vestib Research: Equilib Orientat. 2014;24(5–6):375–85.10.3233/VES-140534
10. Uloziene I Totiliene M Paulauskas A Blazauskas T Marozas V Kaski D Ulozas V Subjective visual vertical assessment with mobile virtual reality system Med (Kaunas) 2017 53 6 394 402
Uloziene I, Totiliene M, Paulauskas A, Blazauskas T, Marozas V, Kaski D, Ulozas V. Subjective visual vertical assessment with mobile virtual reality system. Med (Kaunas). 2017;53(6):394–402.
11. Tamura A Wada Y Kurita A Matsunobu T Inui T Shiotani A Visual effects on the subjective visual vertical and subjective postural head vertical during static roll-tilt Laryngoscope Invest Otolaryngol 2017 2 3 125 30 10.1002/lio2.72
Tamura A, Wada Y, Kurita A, Matsunobu T, Inui T, Shiotani A. Visual effects on the subjective visual vertical and subjective postural head vertical during static roll-tilt. Laryngoscope Invest Otolaryngol. 2017;2(3):125–30.10.1002/lio2.72
12. Davalos-Bichara M Agrawal Y Normative results of healthy older adults on standard clinical vestibular tests Otology Neurotology: Official Publication Am Otological Soc Am Neurotology Soc [and] Eur Acad Otology Neurotology 2014 35 2 297 300 10.1097/MAO.0b013e3182a09ca8
Davalos-Bichara M, Agrawal Y. Normative results of healthy older adults on standard clinical vestibular tests. Otology Neurotology: Official Publication Am Otological Soc Am Neurotology Soc [and] Eur Acad Otology Neurotology. 2014;35(2):297–300.10.1097/MAO.0b013e3182a09ca8
13. Buttner-Ennever JA Patterns of connectivity in the vestibular nuclei Ann N Y Acad Sci 1992 656 363 78 10.1111/j.1749-6632.1992.tb25222.x 1599156
Buttner-Ennever JA. Patterns of connectivity in the vestibular nuclei. Ann N Y Acad Sci. 1992;656:363–78.1599156 10.1111/j.1749-6632.1992.tb25222.x
14. Bittar RSM Sato E Ribeiro DJS Oiticica J Grasel SS Mezzalira R Video head impulse test relevance in the early postoperative period after cochlear implantation Acta Otolaryngol 2019 139 1 6 10 10.1080/00016489.2018.1535194 30664399
Bittar RSM, Sato E, Ribeiro DJS, Oiticica J, Grasel SS, Mezzalira R, et al. Video head impulse test relevance in the early postoperative period after cochlear implantation. Acta Otolaryngol. 2019;139(1):6–10.30664399 10.1080/00016489.2018.1535194
15. Karnath HO Ferber S Dichgans J The neural representation of postural control in humans Proc Natl Acad Sci USA 2000 97 25 13931 6 10.1073/pnas.240279997 11087818
Karnath HO, Ferber S, Dichgans J. The neural representation of postural control in humans. Proc Natl Acad Sci USA. 2000;97(25):13931–6.11087818 10.1073/pnas.240279997
16. Thomas Brandt MD, Michael Strupp. Vertigo and dizziness. 2nd ed. ed: Springer; 2013.
17. Baier B Vogt T Rohde F Cuvenhaus H Conrad J Dieterich M Deep brain stimulation of the nucleus ventralis intermedius: a thalamic site of graviceptive modulation Brain Struct Function 2017 222 1 645 50 10.1007/s00429-015-1157-x
Baier B, Vogt T, Rohde F, Cuvenhaus H, Conrad J, Dieterich M. Deep brain stimulation of the nucleus ventralis intermedius: a thalamic site of graviceptive modulation. Brain Struct Function. 2017;222(1):645–50.10.1007/s00429-015-1157-x
18. Barmack NH Central vestibular system: vestibular nuclei and posterior cerebellum Brain Res Bull 2003 60 5–6 511 41 10.1016/S0361-9230(03)00055-8 12787870
Barmack NH. Central vestibular system: vestibular nuclei and posterior cerebellum. Brain Res Bull. 2003;60(5–6):511–41.12787870 10.1016/S0361-9230(03)00055-8
19. Shinder ME Taube JS Differentiating ascending vestibular pathways to the cortex involved in spatial cognition J Vestib Research: Equilib Orientat 2010 20 1 3 23 10.3233/VES-2010-0344
Shinder ME, Taube JS. Differentiating ascending vestibular pathways to the cortex involved in spatial cognition. J Vestib Research: Equilib Orientat. 2010;20(1):3–23.10.3233/VES-2010-0344
20. Frank SM Greenlee MW The parieto-insular vestibular cortex in humans: more than a single area? J Neurophysiol 2018 120 3 1438 50 10.1152/jn.00907.2017 29995604
Frank SM, Greenlee MW. The parieto-insular vestibular cortex in humans: more than a single area? J Neurophysiol. 2018;120(3):1438–50.29995604 10.1152/jn.00907.2017
21. Cullen KE The vestibular system: multimodal integration and encoding of self-motion for motor control Trends Neurosci 2012 35 3 185 96 10.1016/j.tins.2011.12.001 22245372
Cullen KE. The vestibular system: multimodal integration and encoding of self-motion for motor control. Trends Neurosci. 2012;35(3):185–96.22245372 10.1016/j.tins.2011.12.001
22. Yeo SS Jang SH Kwon JW Central vestibular disorder due to ischemic injury on the parieto-insular vestibular cortex in patients with middle cerebral artery territory infarction: observational study Medicine 2017 96 51 0000000000009349 10.1097/MD.0000000000009349
Yeo SS, Jang SH, Kwon JW. Central vestibular disorder due to ischemic injury on the parieto-insular vestibular cortex in patients with middle cerebral artery territory infarction: observational study. Medicine. 2017;96(51):0000000000009349.10.1097/MD.0000000000009349
23. Yeo SS Jang SH Kwon JW Lateral medullary syndrome following injury of the vestibular pathway to the core vestibular cortex: diffusion tensor imaging study Neurosci Lett 2018 665 147 51 10.1016/j.neulet.2017.12.010 29217256
Yeo SS, Jang SH, Kwon JW. Lateral medullary syndrome following injury of the vestibular pathway to the core vestibular cortex: diffusion tensor imaging study. Neurosci Lett. 2018;665:147–51.29217256 10.1016/j.neulet.2017.12.010
24. Kirsch V Keeser D Hergenroeder T Erat O Ertl-Wagner B Brandt T Dieterich M Structural and functional connectivity mapping of the vestibular circuitry from human brainstem to cortex Brain Struct Function 2016 221 3 1291 308 10.1007/s00429-014-0971-x
Kirsch V, Keeser D, Hergenroeder T, Erat O, Ertl-Wagner B, Brandt T, Dieterich M. Structural and functional connectivity mapping of the vestibular circuitry from human brainstem to cortex. Brain Struct Function. 2016;221(3):1291–308.10.1007/s00429-014-0971-x
25. Pfeiffer C Serino A Blanke O The vestibular system: a spatial reference for bodily self-consciousness Front Integr Nuerosci 2014 8 31 10.3389/fnint.2014.00031
Pfeiffer C, Serino A, Blanke O. The vestibular system: a spatial reference for bodily self-consciousness. Front Integr Nuerosci. 2014;8:31.10.3389/fnint.2014.00031
26. Venhovens J Meulstee J Verhagen WIM Vestibular evoked myogenic potentials (VEMPs) in central neurological disorders Clin Neurophysiology: Official J Int Federation Clin Neurophysiol 2016 127 1 40 9 10.1016/j.clinph.2014.12.021
Venhovens J, Meulstee J, Verhagen WIM. Vestibular evoked myogenic potentials (VEMPs) in central neurological disorders. Clin Neurophysiology: Official J Int Federation Clin Neurophysiol. 2016;127(1):40–9.10.1016/j.clinph.2014.12.021
27. Dieterich M Brandt T Perception of verticality and vestibular disorders of Balance and Falls Front Neurol 2019 10 172 10.3389/fneur.2019.00172 31001184
Dieterich M, Brandt T. Perception of verticality and vestibular disorders of Balance and Falls. Front Neurol. 2019;10:172.31001184 10.3389/fneur.2019.00172
28. Jang SH Kwon HG Connectivity of Inferior Cerebellar Peduncle in the human brain: a diffusion Tensor Imaging Study Neural Netw World 2016 26 5 439 47 10.14311/NNW.2016.26.025
Jang SH, Kwon HG. Connectivity of Inferior Cerebellar Peduncle in the human brain: a diffusion Tensor Imaging Study. Neural Netw World. 2016;26(5):439–47.10.14311/NNW.2016.26.025
29. Zhu Y Chen SR Pan HL Muscarinic receptor subtypes differentially control synaptic input and excitability of cerebellum-projecting medial vestibular nucleus neurons J Neurochem 2016 137 2 226 39 10.1111/jnc.13554 26823384
Zhu Y, Chen SR, Pan HL. Muscarinic receptor subtypes differentially control synaptic input and excitability of cerebellum-projecting medial vestibular nucleus neurons. J Neurochem. 2016;137(2):226–39.26823384 10.1111/jnc.13554
30. Aitken P Zheng Y Smith PF The modulation of hippocampal theta rhythm by the vestibular system J Neurophysiol 2018 119 2 548 62 10.1152/jn.00548.2017 29167325
Aitken P, Zheng Y, Smith PF. The modulation of hippocampal theta rhythm by the vestibular system. J Neurophysiol. 2018;119(2):548–62.29167325 10.1152/jn.00548.2017
31. Wang Q Yap P-T Wu G Shen D Diffusion tensor image registration using hybrid connectivity and tensor features Hum Brain Mapp 2014 35 7 3529 46 10.1002/hbm.22419 24293159
Wang Q, Yap P-T, Wu G, Shen D. Diffusion tensor image registration using hybrid connectivity and tensor features. Hum Brain Mapp. 2014;35(7):3529–46.24293159 10.1002/hbm.22419
32. Assaf Y Pasternak O Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review J Mol Neuroscience: MN 2008 34 1 51 61 10.1007/s12031-007-0029-0
Assaf Y, Pasternak O. Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neuroscience: MN. 2008;34(1):51–61.10.1007/s12031-007-0029-0
33. Wang Y Shen Y Liu D Li G Guo Z Fan Y Niu Y Evaluations of diffusion tensor image registration based on fiber tractography Biomed Eng Online 2017 16 1 9 10.1186/s12938-016-0299-2 28086899
Wang Y, Shen Y, Liu D, Li G, Guo Z, Fan Y, Niu Y. Evaluations of diffusion tensor image registration based on fiber tractography. Biomed Eng Online. 2017;16(1):9.28086899 10.1186/s12938-016-0299-2
34. Wassenaar TM Yaffe K van der Werf YD Sexton CE Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies Neurobiol Aging 2019 80 56 70 10.1016/j.neurobiolaging.2019.04.006 31103633
Wassenaar TM, Yaffe K, van der Werf YD, Sexton CE. Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies. Neurobiol Aging. 2019;80:56–70.31103633 10.1016/j.neurobiolaging.2019.04.006
35. Madden DJ Bennett IJ Song AW Cerebral white matter integrity and cognitive aging: contributions from diffusion tensor imaging Neuropsychol Rev 2009 19 4 415 35 10.1007/s11065-009-9113-2 19705281
Madden DJ, Bennett IJ, Song AW. Cerebral white matter integrity and cognitive aging: contributions from diffusion tensor imaging. Neuropsychol Rev. 2009;19(4):415–35.19705281 10.1007/s11065-009-9113-2
36. Koo BB Bergethon P Qiu WQ Scott T Hussain M Rosenberg I Clinical prediction of fall risk and white matter abnormalities: a diffusion tensor imaging study Arch Neurol 2012 69 6 733 8 10.1001/archneurol.2011.2272 22332181
Koo BB, Bergethon P, Qiu WQ, Scott T, Hussain M, Rosenberg I, et al. Clinical prediction of fall risk and white matter abnormalities: a diffusion tensor imaging study. Arch Neurol. 2012;69(6):733–8.22332181 10.1001/archneurol.2011.2272
37. Smith SM Jenkinson M Woolrich MW Beckmann CF Behrens TE Johansen-Berg H Advances in functional and structural MR image analysis and implementation as FSL NeuroImage 2004 23 1 051
Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(1):051.
38. Jang SH Kwon JW Yeo SS Three dimensional identification of medial and lateral Vestibulospinal Tract in the human brain: a diffusion Tensor Imaging Study Front Hum Neurosci 2018 12 229 10.3389/fnhum.2018.00229 29922138
Jang SH, Kwon JW, Yeo SS. Three dimensional identification of medial and lateral Vestibulospinal Tract in the human brain: a diffusion Tensor Imaging Study. Front Hum Neurosci. 2018;12:229.29922138 10.3389/fnhum.2018.00229
39. Anthofer J Steib K Fellner C Lange M Brawanski A Schlaier J The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation Acta Neurochir 2014 156 8 1497 504 10.1007/s00701-014-2103-z 24829155
Anthofer J, Steib K, Fellner C, Lange M, Brawanski A, Schlaier J. The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation. Acta Neurochir. 2014;156(8):1497–504. discussion 504.24829155 10.1007/s00701-014-2103-z
40. Ferreira MM Cunha F Gananca CF Gananca MM Caovilla HH Subjective visual vertical with the bucket method in Brazilian healthy individuals Braz J Otorhinolaryngol 2016 82 4 442 6 10.1016/j.bjorl.2015.08.027 26895747
Ferreira MM, Cunha F, Gananca CF, Gananca MM, Caovilla HH. Subjective visual vertical with the bucket method in Brazilian healthy individuals. Braz J Otorhinolaryngol. 2016;82(4):442–6.26895747 10.1016/j.bjorl.2015.08.027
41. Downs S Marquez J Chiarelli P The Berg Balance Scale has high intra- and inter-rater reliability but absolute reliability varies across the scale: a systematic review J Physiother 2013 59 2 93 9 10.1016/S1836-9553(13)70161-9 23663794
Downs S, Marquez J, Chiarelli P. The Berg Balance Scale has high intra- and inter-rater reliability but absolute reliability varies across the scale: a systematic review. J Physiother. 2013;59(2):93–9.23663794 10.1016/S1836-9553(13)70161-9
42. Bronstein AM Yardley L Moore AP Cleeves L Visually and posturally mediated tilt illusion in Parkinson’s disease and in labyrinthine defective subjects Neurology 1996 47 3 651 6 10.1212/WNL.47.3.651 8797458
Bronstein AM, Yardley L, Moore AP, Cleeves L. Visually and posturally mediated tilt illusion in Parkinson’s disease and in labyrinthine defective subjects. Neurology. 1996;47(3):651–6.8797458 10.1212/WNL.47.3.651
43. Wirth AM Frank SM Greenlee MW Beer AL White Matter Connectivity of the visual-vestibular cortex examined by diffusion-weighted imaging Brain Connect 2018 8 4 235 44 10.1089/brain.2017.0544 29571264
Wirth AM, Frank SM, Greenlee MW, Beer AL. White Matter Connectivity of the visual-vestibular cortex examined by diffusion-weighted imaging. Brain Connect. 2018;8(4):235–44.29571264 10.1089/brain.2017.0544
44. Tasker RR Organ LW Hawrylyshyn P Investigation of the surgical target for alleviation of involuntary movement disorders Appl Neurophysiol 1982 45 3 261 74 7036856
Tasker RR, Organ LW, Hawrylyshyn P. Investigation of the surgical target for alleviation of involuntary movement disorders. Appl Neurophysiol. 1982;45(3):261–74.7036856
45. Hawrylyshyn PA Rubin AM Tasker RR Organ LW Fredrickson JM Vestibulothalamic projections in man–a sixth primary sensory pathway J Neurophysiol 1978 41 2 394 401 10.1152/jn.1978.41.2.394 306422
Hawrylyshyn PA, Rubin AM, Tasker RR, Organ LW, Fredrickson JM. Vestibulothalamic projections in man–a sixth primary sensory pathway. J Neurophysiol. 1978;41(2):394–401.306422 10.1152/jn.1978.41.2.394
46. Bronstein AM The interaction of otolith and proprioceptive information in the perception of verticality. The effects of labyrinthine and CNS disease Ann N Y Acad Sci 1999 871 324 33 10.1111/j.1749-6632.1999.tb09195.x 10372082
Bronstein AM. The interaction of otolith and proprioceptive information in the perception of verticality. The effects of labyrinthine and CNS disease. Ann N Y Acad Sci. 1999;871:324–33.10372082 10.1111/j.1749-6632.1999.tb09195.x
47. Dieterich M Brandt T Thalamic infarctions: differential effects on vestibular function in the roll plane (35 patients) Neurology 1993 43 9 1732 40 10.1212/WNL.43.9.1732 8414023
Dieterich M, Brandt T. Thalamic infarctions: differential effects on vestibular function in the roll plane (35 patients). Neurology. 1993;43(9):1732–40.8414023 10.1212/WNL.43.9.1732
48. Boiten J Wilmink J Kingma H Acute rotatory vertigo caused by a small haemorrhage of the vestibular cortex J Neurol Neurosurg Psychiatry 2003 74 3 388 10.1136/jnnp.74.3.388 12588938
Boiten J, Wilmink J, Kingma H. Acute rotatory vertigo caused by a small haemorrhage of the vestibular cortex. J Neurol Neurosurg Psychiatry. 2003;74(3):388.12588938 10.1136/jnnp.74.3.388
49. Hyam JA Owen SL Kringelbach ML Jenkinson N Stein JF Green AL Aziz TZ Contrasting connectivity of the ventralis intermedius and ventralis oralis posterior nuclei of the motor thalamus demonstrated by probabilistic tractography Neurosurgery 2012 70 1 162 9 10.1227/NEU.0b013e3182262c9a 22158304
Hyam JA, Owen SL, Kringelbach ML, Jenkinson N, Stein JF, Green AL, Aziz TZ. Contrasting connectivity of the ventralis intermedius and ventralis oralis posterior nuclei of the motor thalamus demonstrated by probabilistic tractography. Neurosurgery. 2012;70(1):162–9. discussion 9.22158304 10.1227/NEU.0b013e3182262c9a
50. Jang SH Lee MY Yeo SS Kwon HG Structural neural connectivity of the vestibular nuclei in the human brain: a diffusion tensor imagingS study Neural Regeneration Res 2018 13 4 727 30 10.4103/1673-5374.230304
Jang SH, Lee MY, Yeo SS, Kwon HG. Structural neural connectivity of the vestibular nuclei in the human brain: a diffusion tensor imagingS study. Neural Regeneration Res. 2018;13(4):727–30.10.4103/1673-5374.230304
51. Yeo SS Kwon JW Cho IH Associations between Age-related changes in the core vestibular projection pathway and balance ability: a diffusion Tensor Imaging Study Behav Neurol 2020 2020 2825108 10.1155/2020/2825108 32104515
Yeo SS, Kwon JW, Cho IH. Associations between Age-related changes in the core vestibular projection pathway and balance ability: a diffusion Tensor Imaging Study. Behav Neurol. 2020;2020:2825108.32104515 10.1155/2020/2825108
52. Arshad Q Seemungal BM Age-related vestibular loss: current understanding and future research directions Front Neurol 2016 7 231 10.3389/fneur.2016.00231 28066316
Arshad Q, Seemungal BM. Age-related vestibular loss: current understanding and future research directions. Front Neurol. 2016;7:231.28066316 10.3389/fneur.2016.00231
