Abstract
Background
Emerging evidence indicates an association between vestibular dysfunction and Depersonalization/Derealization (DD) symptoms. However, substantial heterogeneity in the studied populations, experimental paradigms, and assessment methodologies limits clear conclusions regarding the involvement of the vestibular system in the onset of DD symptoms.
Objective
To clarify the contribution of the vestibular system to DD symptoms in vestibular patients and healthy individuals undergoing vestibular stimulation.
Methods
Following PRISMA guidelines, we reviewed studies examining: (1) DD symptoms in vestibular patients, and (2) DD symptoms in healthy individuals during vestibular stimulation.
Results
Twenty-three studies met the inclusion criteria. Among these, 86.9% reported DD symptoms either in patients with vestibular disorders (14/15) or in healthy individuals during vestibular stimulations (6/8). Additionally, 82.61% of the studies identified an association between DD symptoms and anxiety or spatial disorientation.
Conclusions
Together, these findings indicate that vestibular alterations may contribute to the emergence of DD symptoms. Anxiety and spatial disorientation were found to frequently co-occur suggesting an interaction between vestibular processing, affective regulation, and spatial cognition. This association can be interpreted within a neurofunctional framework, which posits that vestibular alterations disrupt multisensory integration in parietotemporal, insular, and hippocampal regions, contributing to the core phenomenology of DD.
Keywords
Introduction
Bodily self-consciousness (BSC), the subjective experience of perceiving oneself as a coherent entity within the body and the surrounding space, is a fundamental requirement for human cognition and psychological well-being. This complex phenomenon encompasses several key components, including the experience of owning a body (or body ownership), the perception of occupying a specific spatial location (or self-location), and the ability to adopt a body-centered perspective from which to perceive the world (or first-person perspective).1–3 BSC relies on the integration of multisensory bodily afferent signals, which come from external (i.e., tactile, auditory, and visual information) and internal (i.e., interoceptive, proprioceptive, and vestibular signals) sources, 2 efferent motor signals and cognitive processes.1,4 Dysfunctional integration of these signals can lead to disturbances in maintaining a coherent sense of self. 5
A frequently overlooked yet significant phenomenon associated with altered BSC is the emergence of Depersonalization-Derealization (DD) symptoms. Depersonalization involves a feeling of partial or complete detachment from one’s own body and/or mental processes, leading to disturbances in body ownership, agency, first-person perspective, and self-location as well as emotional dysregulation (i.e., emotional numbing). Derealization, on the other hand, is marked by a sense of detachment and unreality concerning the external environment.6,7 When DD experiences become chronic and distressing, they may lead to Depersonalization and Derealization Disorder (DDD), a condition with significant implications for daily functioning.7,8 The severity and prevalence of DD symptoms are well-documented in clinical populations. Epidemiological studies indicate that approximately 70% of individuals experience at least one episode of DD in their lifetime, with ∼2% meeting the criteria for chronic DD. 7 This percentage is notably higher in psychiatric populations, where rates range from 3.3% to ∼50%.9,10 DD symptoms show high comorbidity with various psychiatric disorders, such as depression, bipolar personality disorder, and schizophrenia.8,10
In recent decades, it has been hypothesized that the vestibular system, which is mainly known for its role in postural control and balance, plays also a role in BSC (for a review, see 11) and therefore it might also be implicated in DD symptoms. Indeed, damages to this system have been associated with DD symptoms12–15 and even with Out-of-Body Experiences (OBEs, 16 ). Additionally, people suffering from DD often experience common vestibular symptoms, such as spatial disorientation, vertigo and dizziness. 17 Critically, longitudinal studies are needed to better understand whether alterations to the vestibular system can cause the onset of DD symptoms. This is clinically relevant, as 8.4% of American adults experience vestibular vertigo each year, 18 with 2.98% diagnosed with a vestibular disorder. 19
Although the putative contribution of the vestibular system to DD symptoms is still poorly understood (for a narrative review see: 20 ), its role in the generation of BSC has long been investigated (for a review see, 21 ). Specifically, by encoding head and trunk movements in three-dimensional space and the body position with respect to the surrounding environment, vestibular signals contribute to the neural computations underlying spatial aspects of BSC, in particular self-location and first-person perspective. 22 This is supported by the evidence that patients diagnosed with peripheral vestibular disorders manifest impairments in both spatial navigation and body orientation23–25 as well as difficulties in egocentric mental transformations. 26 Additional support to this hypothesis comes from studies artificially modulating the vestibular input, using Galvanic Vestibular Stimulation (GVS) or Caloric Vestibular Stimulation (CVS). For example, healthy individuals undergoing experimental vestibular modulations experience disturbances of body ownership,27,28 of body perception, 29 and of spatial orientation.30–32 Moreover, left-ear CVS improves body representation and spatial awareness in patients with somatoparaphrenia 33 or unilateral spatial neglect. 34
Despite the evidence linking the vestibular system to BSC, the precise role of the vestibular system on the emergence of DD symptoms remains unclear. Most studies have focused on the relationship between the vestibular system and specific aspects of BSC, often without directly taking into consideration DD symptoms. Even among studies that have considered these symptoms, the heterogeneity of clinical populations, experimental designs, and assessment methods prevents a comprehensive understanding of this relationship.
With this work we provide a detailed analysis of the vestibular system involvement in the experience of DD symptoms, by systematically reviewing the scientific literature on (i) the presence of DD symptoms in patients with vestibular disorders, and (ii) the induction of DD symptoms by artificial vestibular stimulations in healthy individuals. We also critically discuss current neurofunctional interpretations of the link between vestibular function and DD symptoms. Gaining a deeper understanding of this relationship is crucial, as it will enhance our comprehension of the vestibular system role in DD, ultimately contributing to the development of more effective diagnostic and prognostic tools as well as therapeutic strategies for the treatment of dissociative symptoms in vestibular and psychiatric patients.
Methods
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were applied
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(see Figure 1) to set the structure and procedure. Articles were searched on the following online databases: PubMed, PsycINFO, Web Of Science, and Scopus using the string “((vestibular system) OR (vestibular disorders) OR (vestibular diseases) OR (vestibular impairments) OR (caloric vestibular stimulation) OR (galvanic vestibular stimulation)) AND ((depersonalization) OR (derealization) OR (dissociative disorders)).” Studies—published between 1989 and 2024—were selected according to the following inclusion criteria: (1) assessment of DD symptoms in patients with vestibular disorders or in healthy individuals following vestibular manipulations; (2) written in English; and (3) free full text available. The identified studies were categorized into (i) studies involving vestibular patients and (ii) studies involving artificial vestibular stimulation in healthy individuals. Within the first category, articles were further classified based on their research design,
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while in the second category, they were classified based on the employed stimulation technique. A risk of bias assessment was conducted for each study using the Joanna Briggs Institute (JBI) critical appraisal tool.
37
For each question, a positive, negative, or unclear answer was given and then studies were classified based on their risk of bias level: >70 % represented low risk of bias, <70 % represented moderate risk of bias, and <50 % represented high risk of bias. For each study, two judges independently assessed the risk of bias, with a third judge consulted to solve any discrepancy. Flow chart of the article selection process following the PRISMA guidelines.
Results
Summary of studies investigating DD symptoms in patients with vestibular disorders and in healthy volunteers undergoing vestibular stimulations.
Legend: CDS = Cambridge Depersonalization Scale; CVD = central vestibular disorder; CVS = caloric vestibular stimulation; DDI = Depersonalization and Derealization Inventory; DES = Dissociative Experiences Scale; HI = healthy individuals; MRI = magnetic resonance imaging; PPPD = persistent postural perceptual dizziness; pBVH = peripheral bilateral vestibular hypofunction; PVD = peripheral vestibular disorders; MJD = Machado Joseph disease; VD = vestibular disorder; VS = vestibular stimulation.
Vestibular disorders and DD symptoms
The 15 studies that investigated DD symptoms in patients with vestibular disorders included patients with peripheral or central vestibulopathy and neurological patients with vertigo and dizziness. Three studies were classified as case studies/case series,38–40 two as cohort studies,41,42 and 10 as cross-sectional studies.12–14,16,17,29,43–46 Studies are presented according to the experimental design (Table 1).
Case series/case study
Three case series described the association between vestibular disorders and DD symptoms. In their article, Grigsby and Johnston 39 described two young women diagnosed with Meniere’s disease, both associating DD symptoms to vertigo episodes, while only one to anxiety symptoms. Similarly, Sun and colleagues 40 described an adult man who reported depersonalization concomitant with vertigo symptoms originating from disturbances of the left otolithic organ. Gamble and colleagues 38 used semi-structured interviews to analyze the phenomenological experiences of 6 persistent postural perceptual dizziness (PPPD 47 ) patients. Two out of six patients reported depersonalization symptoms and autoscopic phenomena, such as OBEs and other dissociative experiences, which were often associated with anxiety. In all three cases, depersonalization symptoms were described as the sensation of disconnection from one’s own body, as expressed through sentences such as: “I feel like I’m outside of myself,” “I’m floating outside of the body,” or “I’m not actually being there or having anything to do with my body.” These reports provide qualitative evidence supporting a link between vestibular disorders, DD symptoms and in many cases also anxiety.
Cohort studies
Gómez-Alvarez and Jáuregui-Renaud 42 recruited 10 patients diagnosed with unilateral peripheral vestibular disorders to assess the correlation between spatial orientation, DD symptoms, balance and psychological symptoms (anxiety, depression, and general health) during 3-months follow-up. They tested patients’ spatial orientation abilities using the Subjective Visual Vertical (SVV)—which required participants to position a line according to their perceived body midline—and an orientation updating test, in which they had to report which wall they were facing after five blindfolded rotations. DD symptoms were assessed using both Depersonalization-Derealization Inventory (DDI) and Dissociative Experience Scale (DES). The authors additionally examined: balance symptoms (nine-item in-house questionnaire); self-perceived impairment (Dizziness Handicap Inventory, DHI); general health (12-item General Health Questionnaire, GHQ-12); anxiety (Zung Instrument for Anxiety Disorders, ZIAD); and depressive symptoms (17-item Hamilton Depression Rating Scale, HDRs). Results showed that, at the 3-month follow-up, patients significantly improved their performance in spatial tasks and DD symptoms compared to the first week. Notably, DDI (but not DES) scores were positively correlated with balance symptoms and with decreases in spatial reorientation errors.
Alessandrini and colleagues 41 employed Positron Emission Tomography (PET) to keep track of cortical metabolic alterations and psychological changes following the onset of vestibular neuritis. They recruited 8 patients diagnosed with vestibular neuritis and tested them 48 h after the diagnosis (T0) and after 1 month (T1). They also recruited 30 matched Healthy Controls (HC). Balance symptoms were assessed with a nine-item in-house questionnaire; anxiety and DD symptoms were assessed with the ZIAD and the DDI, respectively. Patients showed a significant reduction in balance symptoms, anxiety and DD symptoms at T1 compared to T0, with no differences between groups at T1. Interestingly, hypermetabolism found in parahippocampal, temporal and cingulate cortices in the acute phase of the vestibular neuritis was positively correlated with DDI scores suggesting that greater metabolic activity in these areas was associated with more DD symptoms.
The results of these two studies suggest that DD symptoms may arise after unilateral peripheral vestibular lesions, gradually diminishing over time. Interestingly, anxiety, balance symptoms and spatial disorientation proved to be factors associated with this relationship.
Cross-sectional studies
Four cross-sectional studies investigated the presence of DD symptoms in individuals experiencing dizziness. In the first study, Tschan and colleagues 17 investigated the association between DD symptoms and dizziness in the non-clinical population by comparing 201 individuals who spontaneously reported experiencing dizziness with 1068 individuals who did not. DD symptoms were assessed with the short version of the Cambridge Depersonalization Scale (CDS-9), social phobia with the 3-item Social Phobia Inventory and anxiety with the Generalized Anxiety Disorder Scale (GAD-7), panic disorder were assessed with the Patient Health Questionnaire (PHQ), and depressive symptoms with the 2-item depression module of the PHQ. Vertigo and dizziness were evaluated using the Vertigo Symptom Scale and specific questions (e.g., “How strong was dizziness in the past 4 weeks?”). Results showed that 62.7% of individuals who reported dizziness also experienced at least one DD symptom—compared to 21.2% in the non-dizziness group. In addition, participants who reported being significantly affected by DD symptoms in their daily lives, or that met the criteria for clinically relevant DD symptoms were ten times more likely to be included in the dizziness group than in the group without dizziness, even after controlling for other psychological factors. Lastly, anxiety, depressive symptoms, panic disorder and social phobia were also more common in individuals with dizziness compared to the group without dizziness.
Two studies 16 and 29 study 1 investigated the relation between DD symptoms and dizziness in both clinical and non-clinical populations. Indeed, 60 patients with dizziness in the first study 29 study 1, and 210 in the second study 16 were recruited, together with a matched number of HC. In both studies, DD symptoms were assessed with the long version of the CDS (CDS-29). In the second study, anxiety and OBEs were assessed via the Hospital Anxiety and Depression Scale (HADS) and the Palmer’s questionnaire, respectively. In both studies, DD symptoms were found to be significantly higher in the patients groups compared to controls. Notably, in the second study 16 CDS scores were found to predict OBEs and to be associated with anxiety in both groups. In addition, patients with OBEs were more prone to experience migraine.
Lastly, Toupet and colleagues 46 further explored the association between DD symptoms and dizziness in the clinical population in a prospective cross-sectional study. They recruited 319 patients with chronic dizziness and assessed: DD symptoms with the DDI, anxiety and depressive symptoms with the HADS, and visual and vestibular hypersensitivity with an in-house questionnaire and with the Dizziness in Daily Activities (DDA) questionnaire. Also in this study, patients with a migraine history manifested significantly more DD symptoms than those without a migraine history. Interestingly, DD symptoms were more frequent during vertigo spells, and in patients with higher anxiety and depressive symptoms.
Six cross-sectional studies investigated the relation between vestibular disorders and DD symptoms, as well as anxiety and/or spatial orientation as associated factors in this relationship.
In two studies, Jáuregui-Renaud and colleagues investigated the association between vestibular disorders and DD symptoms.13,43 In the first study they compared the spatial orientation abilities (assessed as in 42) and DD symptoms of 50 patients with peripheral vestibular disorders with those of 60 HC. In the second study, they compared DD symptoms in three groups of patients: 40 diagnosed with vestibular disorders, 40 with hearing loss, 40 with retinal disorders, and 80 HC. In both studies, DD symptoms and general health were assessed with the DDI and the GHQ-12, respectively. Results revealed significantly higher DDI scores in vestibular patients than in healthy individuals in the first study and higher DDI scores in vestibular and retinal patients compared to patients with hearing disorders and healthy controls in the second study. In addition, positive correlations were observed between DDI scores and disturbances of the general health status (including anxiety and depressive symptoms) in both studies, and between DDI scores and spatial estimation errors in the first study.
The role of anxiety in the relationship between vestibular disorders and DD symptoms was further explored by Kolev and colleagues. 14 In their study, they recruited 42 patients with peripheral vestibular disorders: 24 with concomitant anxiety and 18 without anxiety—assessed with the HADS—along with 18 HC. DD symptoms were assessed with the DDI. Results showed that DDI scores were significantly higher in vestibular patients compared to HC. Furthermore, patients with concomitant anxiety exhibited higher DDI scores compared to those without anxiety, and a positive correlation between DD symptoms and anxiety.
Elyoseph and colleagues 12 investigated potential differences in DD symptoms, spatial orientation, and anxiety in patients with peripheral or central vestibular disorders and in healthy volunteers. They recruited 14 patients with peripheral Bilateral Vestibular Hypofunction (pBVH), 19 patients with Machado Joseph Disease (MJD) and 20 HC. DD symptoms were assessed with the DDI, spatial skills with the Objective Perspective Taking test, and anxiety with the Body Sensation Questionnaire (BSQ). Results showed significantly more DD symptoms in the pBVH group compared to the MJD group and the control group. Moreover, regression analysis showed that the severity of DD symptoms in the pBVH group was predicted by both spatial abilities and anxiety scores.
Two studies by Jáuregui-Renaud and colleagues44,45 explored the contribution of spatial anxiety, a type of anxiety specifically related to performances in spatial tasks, perspective taking and individual factors, including DD symptoms, in dizziness related handicap. They recruited 153 patients diagnosed with peripheral vestibular disorders and 156 HC in the first study, 44 53 PPPD patients and 53 HC in the second study. 45 Both studies included a spatial task and psychological questionnaires to investigate the correlation between vestibular disorders, DD symptoms, spatial abilities and psychological factors. In the first study, the spatial task consisted of an Object Perspective Taking task, in which participants viewed multiple objects and had to answer questions about the spatial relations between objects after mentally adopting a particular viewpoint. In the second study, the spatial task consisted of a SVV task. In both studies spatial anxiety was assessed with the Spatial Anxiety Scale-10 (SAS-10), unsteadiness with a nine-item standardized questionnaire, anxiety and depression with the HADS, perceived stress with the Perceived Stress Scale-10 (PSS-10), and perceived handicap with the Dizziness Handicap Inventory (DHI). Only in the first study, sleep quality and motion sickness were evaluated with the Pittsburgh Sleep Quality Index (PSQI) and the Motion Sickness Susceptibility Questionnaire (MSSQ), while anxiety was further assessed with the STAI. The results of these studies show decreased spatial abilities in vestibular patients compared to controls, with larger orientation deviations in the OPT, and less precision in the SVV. In addition, while only in the second study higher DD symptoms were observed in the patients compared to controls, in both studies DD symptoms were positively correlated with multiple factors including anxiety, spatial anxiety, unsteadiness, perceived stress and handicap. Lastly, the contribution of these multiple factors, and in particular of spatial anxiety, in spatial task performance was also highlighted in both studies.
Overall, these results suggest that both vestibular symptoms in the non-clinical population and vestibular disorders in the clinical population are associated with DD symptoms. Additionally, spatial abilities and anxiety seem to be linked to this relationship.
Experimental manipulation of the vestibular system and DD symptoms
The 8 studies that have investigated the link between artificially induced vestibular modulations and DD symptoms have employed different techniques such as Caloric Vestibular Stimulation (CVS),15,29,48,49 unilateral centrifugation,50–52 and magnetic-induced stimulation. 53 One study used both CVS and unilateral centrifugation. 50 Each vestibular stimulation technique targets specific components of the vestibular system (for a comprehensive review, see 54), therefore the studies will be organized based on the type of stimulation employed (Table 1).
Caloric vestibular stimulation (CVS)
Four studies employed CVS to modulate the vestibular system. CSV is a technique that can be performed by irrigating outer ear canals with cold and warm liquids or gases to opposite ears (bilateral CVS), or by pouring water to a single ear (unilateral CVS). Although the exact mechanism by which CVS works is not yet fully understood, it is commonly attributed to changes in temperature between the inner and outer ear which are thought to modulate the vestibular input by acting on endolymphatic flow. CVS is known to predominantly act on horizontal semicircular canals. 54
In a quasi-experimental study, Sang and colleagues 15 investigated DD symptoms in 121 healthy individuals and 50 patients with peripheral vestibular disorders undergoing CVS (30/44°C cold water in left/right ears in a counterbalanced manner). DD symptoms were assessed with the DDI and the general health status with the GHQ-12. Results showed that CVS did not affect DD symptoms in vestibular patients, while they significantly increased during stimulation in healthy individuals, matching those experienced by the vestibular patients. Furthermore, DDI scores positively correlated with age in healthy subjects and with anxiety in vestibular patients.
More recently, Lopez and colleagues 48 investigated the contribution of CVS on the representation of body metric properties and DD symptoms. In the first experiment, 18 right-handed healthy individuals were recruited. Two blocks of CVS (47°C warm air in the right ear and 20°C cold air in the left ear in a counterbalanced manner) and two blocks of Sham stimulation (37°C body temperature air in both ears) were administered in a counterbalanced order. During both CVS and Sham stimulation, body metric properties were assessed by administering a tactile distance comparison task between two body parts (left hand and forehead), while DD symptoms were assessed with the DDI. Results showed that during CVS individuals reported significantly higher DDI scores compared to Sham, with “feeling spacy,” “being detached from your own body and the surroundings,” and “Not being in control of the Self” as main symptoms. In addition, the same distance applied to the hand—but not on the forehead—was judged to be longer during CVS than during sham. To explore the possibility that this effect was mediated by the right-lateralized representation of the left hand, the authors replicate the study focusing on the effects of CVS on left-hand metric properties. In the follow-up experiment, 17 right-handed healthy individuals were assessed with a localization task of anatomical landmarks on their left hand. Also in this case, the perceived length and width of the left hand and DD symptoms increased during CVS compared to Sham.
In a more recent study, Lopez and colleagues 29 study 2 further investigated the role of the vestibular function in hand representation and DD symptoms by administering the same stimulation procedure of the previous study to 16 healthy right-handed individuals. They adapted the localization task to assess the perceived width and length of participants’ hands. Results showed that CVS—independently of the side of stimulation—significantly increased DD Symptoms compared to the Sham stimulation, and left-warm/right-cold CVS significantly increased the perceived length of the left hand. However, no correlation was found between DDI scores and alterations in the perceived length of the participants’ left hand.
A study by Sedda and colleagues 49 sought to better understand the vestibular contribution to body representation and DD symptoms. The authors recruited 13 healthy volunteers who underwent CVS (0°C cold water in the left ear). Behavioral measures and questionnaires were administered before CVS, immediately after CVS, and 50 min after CVS. Body representation was assessed with two measures: Body temperature of upper limbs (used as a measure of disembodiment), and the Two Point Discrimination task—in which participants were stimulated with a mechanical caliper with their arms set at increasing distances until the participants reported to feel two separated tactile stimulations. DD symptoms and anxiety were assessed using the DDI and the STAI, respectively. Results showed that, compared to baseline and to 50 min after CVS, soon after CVS the body temperature of both arms significantly decreased and restored after 50 min. Moreover, 50 min after CVS, tactile acuity significantly increased and DDI scores significantly decreased compared to the other two time points. Anxiety scores did not statistically change at any time point.
This evidence showed that DD symptoms may emerge as a result of vestibular stimulation, further emphasizing the role of vestibular input alteration as a triggering factor of DD symptoms.
Unilateral centrifugation
Three studies employed unilateral centrifugation to modulate the vestibular input, exposing participants to unilateral centrifugal forces through a rotatory chair that is known to mainly stimulate horizontal canals. 54 In all three studies participants were exposed to rotations that reached a peak velocity of 300°/s at 3.5 cm rotating clockwise or counterclockwise.50–52
In a quasi-experimental design study, Aranda-Moreno & Jáuregui-Renaud 51 investigated the emergence of DD symptoms in 100 healthy individuals following unilateral centrifugation. Psychological evaluation consisted of different standardized questionnaires, assessing: DD symptoms (DDI) pre- and post-stimulation, anxiety levels (ZIAD), depressive symptoms (HDRs), and unsteadiness (9-item questionnaire). Post-stimulation, DDI scores significantly increased compared to pre-stimulation. Interestingly, DDI scores were positively correlated with unsteadiness, anxiety and depressive symptoms before the stimulation and with unsteadiness and depressive symptoms after the stimulation.
In another quasi-experimental study, Jáuregui-Renaud and colleagues 52 investigated the putative induction of DD symptoms by unilateral centrifugation. They recruited 47 patients with type 2 diabetes mellitus (a medical condition sometimes associated with otolithic impairments) and no history of vestibular disorders or vertigo, along with 50 HC. Concomitant to vestibular stimulation, participants were administered the SVV. Psychological evaluation was conducted as in the previous study. Results showed that both patients and controls experienced significantly higher DDI scores after centrifugation compared to before centrifugation. Moreover, while before centrifugation patients had higher DDI scores compared to controls, this difference disappeared after stimulation. Notably, DDI scores were influenced by depressive symptoms and SVV changes before the stimulation, while after the stimulation only depressive symptoms exerted an influence on DDI scores.
In a non-randomized crossover design study, Aranda-Moreno and colleagues 50 investigated the contribution of the vestibular system on DD symptoms and phantom limb pain sensations. The authors recruited 34 patients with unilateral supracondylar amputation after type 2 diabetes mellitus. Participants underwent two experimental sessions, with a randomized assignment to either CVS (same procedure as described in 15) or unilateral centrifugation (same procedure as in 52). The Lattinen index and the Douleur Neuropathique 4 Questions (DN4) questionnaire were administered to assess pain characteristics, while DES, ZIAD, HDRs, and GHQ-12 were administered to assess DD symptoms, anxiety, depressive symptoms, and general health, respectively. The results showed that both CVS and unilateral centrifugation significantly reduced phantom limb pain after the first stimulation, and both stimulations led to a reduction in DD symptoms.
Other forms of artificial vestibular stimulation
So far, we reviewed studies using direct stimulation of the vestibular system. However, there are other techniques that do not have the primary goal of stimulating the vestibular system, yet indirectly alter the vestibular input, such as magnetic stimulation. The effects of this technique on DD symptoms are presented in the following paragraph.
In a quasi-experimental study, Martinez-Gallardo and colleagues 53 tested the ability of a 3T magnetic resonance imaging (MRI) scanner to induce DD symptoms, anxiety, and self-motion perception in a group of 47 healthy individuals. Participants underwent 5 min MRI exposures once a week for 2 weeks. DD symptoms were assessed with the DDI and anxiety was measured with the short version of the STAI. Both measures were performed pre- and post-MRI. Participants were asked to keep notes of potential dizziness and disorientation in the week between the two exposures. The results showed that during and after the first MRI exposure, 40% of the sample experienced self-motion perception. Dizziness was reported both after the first and second MRI exposure. DDI scores significantly increased only after the first MRI exposure and only in those who experienced self-motion perception. In particular, the direction with which the subjects entered the scanner (head vs feet), the mean hours of sleep per week, and motion perception influenced DDI scores. Finally, DDI scores positively correlated with STAI scores both pre and post the first exposure to the MRI stimulation.
These findings show that, similarly to the results obtained with CVS and unilateral centrifugation, DD symptoms can be observed following magnetic vestibular stimulation. These symptoms were associated with factors such as anxiety, sleep time, and previous experience with the stimulation.
Risk of bias
Methodological quality of reviewed studies.
Legend: green circle = yes; red circle = no; yellow circle = unclear; Na = not applicable; VD = vestibular disease; VS = vestibular stimulation; CF = confounding factors; ITT = intention-to-treat.
Summary
A total of 23 studies investigating the relationship between vestibular alterations and DD symptoms were identified. Among them, 15 studies focused on patients with vestibular disorders, while 8 studies investigated healthy individuals undergoing different types of vestibular modulations (see Table 1).
Participants
The reviewed studies included a total of 3537 participants (female = 2090; male = 1409). The total sample size does not correspond to the sum of male and female participants due to missing [48] or inconsistent sex reporting [12] in two studies. Apart from13,42 that balanced females/males ratio, female participants were the majority in 17 out of 23 studies (73.9%). Lopez and colleagues 48 did not report the females/males ratio. With the exception of 4 studies that employed participants under 30 years of age,29,48,49,53 all studies included adults with an average age of 49.1 ± 6.5 years old.
Vestibular alterations
Number of vestibular patients with different vestibular disorders in the reviewed studies. Orange cells indicate the presence of DD symptoms in patients with a specific vestibular disorder according to each study.
PA = peripheral acute; PC = peripheral chronic; C = central; NA = not otherwise specified.
further details on the specific number of patients within this etiology are not reported in the study. As a result, the column “total,” which reports the number of patients for each etiology, does not incorporate the data from this study.
Main evidence and correlated factors
In total, 20 out of 23 of the reviewed studies (86.9%) reported an increased rate of DD symptoms in both patients with vestibular disorders (14/15) and healthy individuals after vestibular stimulation (6/8) (see Table 1). Of all, 19 out of the 23 reviewed studies (82.61%) identified anxiety and/or spatial disorientation as factors significantly associated with DD symptoms. In particular, DD scores were found to correlate with spatial disorientation in 3 studies involving vestibular patients.12,13,42 Moreover, DD symptoms were associated with higher levels of anxiety in 13 studies involving vestibular patients12–17,38,39,41,43–46 and in 3 studies using vestibular stimulations.15,51,53 Finally, DD symptoms and OBEs were associated with migraine in two studies.16,46
Assessment tools
Questionnaires employed in the reviewed studies.
Legend: DDI = Depersonalization and Derealization Inventory; DES = Dissociative Experiences Scale; CDS = Cambridge Depersonalization Scale; ZIAD = Zung Instrument for Anxiety Disorders; GAD-7 = Generalized Anxiety Disorder Scale; HADS = Hospital Anxiety and Depression Scale; BSQ = Body Sensation Questionnaire; SAS-10 = Spatial Anxiety Scale; STAI = State-Trait Anxiety Inventory; HDR = Hamilton Depression Rating Scale; PHQ = Patient Health Questionnaire; DHI = Dizziness Handicap Inventory; SQSU = Standardized Questionnaire of Symptoms related to Unsteadiness; VSS = Vertigo Symptom Scale; DDA = Dizziness in daily life activities; MSSQ = Motion Sickness Susceptibility Questionnaire; GHQ-12 = General Health Questionnaire; PSQI = Pittsburgh Sleep Quality Index; SPI = Social Phobia Inventory; DN4 = Douleur Neuropathique 4; N = number of reviewed studies that employed each questionnaire.
Research design
Overall, 10 out of 15 studies (66.67%) involving vestibular patients were classified as cross-sectional studies, 2 out of 15 as cohort studies (13.33%), 2 out of 15 as case series (13.33%), and the remaining one as a single case study (6.67%). Among the studies that employed vestibular stimulations in healthy individuals, 3 out of 8 (37.5%) were randomized controlled trials, while 5 out of 8 were quasi-experimental studies (62.5%). Overall, 18 out of 23 studies (78.26%) had a low risk of bias.
In the following section, we discuss the significance of these findings in light of the specific role of factors associated with DD symptoms and vestibular dysfunctions, such as spatial disorientation and anxiety.
Discussion
This review aimed to analyze existing evidence and enhance our understanding of the relationship between vestibular alterations and Depersonalization and Derealization (DD) symptoms. Besides pioneering works on single cases,
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frequent episodes of DD have been documented in association with vestibular disorders12–14,16,29,38,42,43 and with dizziness.16,17,29,40,46 The reviewed literature shows that vestibular disorders—especially peripheral—and vestibular stimulations in healthy individuals are associated and can elicit DD symptoms, respectively. Furthermore, the reviewed studies reveal that this relationship is significantly associated with two key factors, namely spatial disorientation and anxiety (Figure 2), as discussed in more detail below. Model of how vestibular alterations lead to DD symptoms. When the vestibular input is altered by otoneurological causes or artificial stimulations it leads to a state of dissonance (i.e., predictive error) that, in turn, leads to an up-weighting of other sensory information over vestibular ones, leading to DD symptoms. In individuals who are predisposed, this may lead to anxiety that can be mitigated, when overwhelming, by inducing emotional numbing, a core feature of DD.
Vestibular contributions to spatial orientation and depersonalization symptoms
The results of the present analysis indicate that spatial disorientation may play a relevant role in the relationship between DD symptoms and the vestibular system. Spatial orientation is a complex cognitive function that enables individuals to be aware of their body position and movement relative to the surrounding environment. Disruptions in spatial orientation can manifest as spatial disorientation, characterized by confusion regarding one’s position, direction or motion. All three studies that explicitly investigated the role of spatial disorientation have associated this feature with the severity of DD symptoms in patients with bilateral vestibular loss, 13 unilateral vestibular loss, 42 or bilateral vestibular hypofunction. 12
The critical role of the vestibular system in spatial orientation is well-documented.24,79–84 Artificial vestibular stimulation leads to difficulties in constructing an egocentric, first-person perspective85,86 and in encoding the spatial coordinates of self-movements. 87 Once vestibular signals are transmitted from peripheral organs to the central nervous system they are integrated with other afferent and efferent signals, including visual, somatosensory, proprioceptive and motor signals,88,89 to generate a spatial representation of the body and its actions relative to gravity and the external environment.21,22,90 Indeed, the vestibular system projects to higher-order association regions such as the TPJ, the cingulate cortex, the precuneus, the insula, and to the hippocampus. 91 These areas not only process vestibular information but also underlie spatial cognition and bodily self-consciousness.92,93 For example, TPJ receives multimodal information and is involved in body representation, 94 orienting of visuospatial attention,95–97 and in distinguishing between the self and the external environment. 98 Notably, structural and functional alterations in TPJ have been found both in patients with vestibular disorders 99 and in those with DD symptoms.100–102 Moreover, stimulating at increasing intensities the right TPJ has been found to transform initial vestibular symptoms into DD experiences, 103 highlighting the crucial role of this region in linking the vestibular system to DD symptoms. Moreover, both the cingulate cortex and the precuneus are implicated in bodily self-consciousness93,104 and alterations in these structures have been associated with DD symptoms.92,105 Finally, the hippocampus—well-known for its role in spatial navigation—is critically involved in processing body position relative to spatial representations of the surrounding environment. 106 Patients with bilateral vestibular loss often report spatial navigation deficits associated with hippocampal atrophy.24,81
In light of this evidence, it is reasonable to hypothesize that altered vestibular input to a wide range of regions including TPJ, precuneus, cingulate cortex, insula, and hippocampus may disrupt the integration between the bodily self and the environment, potentially triggering DD symptoms in addition to spatial disorientation. To summarize, the high incidence of DD symptoms in patients with vestibular disorders and its association with spatial disorientation may reflect the specific contribution of the vestibular system to spatial aspects of bodily self-consciousness, such as self-location and first-person perspective.
The impact of anxiety on the relationship between vestibular alterations and DD symptoms
In most of the reviewed studies, anxiety was associated with both DD symptoms and vestibular dysfunctions. In particular, anxiety was found to be associated with DD symptoms in patients with acute and chronic vestibular disorders,14–16,39,41,43,44 PPPD,38,45 chronic dizziness, 46 and vestibular disorder of unknown origin 17. In healthy individuals, studies using experimental manipulations of vestibular input offer a less clear picture. Some studies showed that DD symptoms were associated with high anxiety levels after CVS, 15 unilateral centrifugation, 51 and magnetic stimulation, 53 while other studies showed that CVS affected DD scores without influencing anxiety levels. 49 This partial discrepancy might be due to the use of different types of anxiety evaluation questionnaires (for a complete list, see Table 4). Moreover, all studies relied on questionnaires that measured state anxiety, as they were specifically interested in capturing anxiety levels within a given time frame. However, assessing trait anxiety (a stable dispositional tendency to experience anxiety) may explain the heterogeneity in the observed results and could provide additional insights into its role in the relationship between vestibular alterations and DD symptoms.
The association between the vestibular system and anxiety has been explored for decades. Today we know that people with anxiety, even in absence of peripheral vestibular loss, 107 often report vestibular symptoms, especially dizziness. At the same time, individuals with vestibular disorders may also experience anxiety.108–112 However, it is still unclear whether these symptoms arise as a response to the emotional distress of living with a vestibular disorder, or if they arise from physiological changes in the brain’s neural circuits following vestibular loss. One of the main hypotheses is that the fear of falling, commonly associated with vestibular disorders, can generate significant anxiety. 113 The continuous perception of instability and difficulty in maintaining balance can induce a constant state of alertness and fear of falling, which may translate into anxiety.113,114 An alternative hypothesis is that the vestibular system has direct influence on emotional regulation networks. Recent research shows that the vestibular system is intricately linked to brain structures involved in emotional response, including cortical and subcortical regions associated with anxiety. 115 One of the most comprehensive models is the one proposed by Balaban, 116 which identifies the parabrachial nucleus (PBN) as a key structure for emotional regulation through its connections with areas such as the hypothalamus, amygdala, and orbitofrontal cortex, regions implicated in anxiety and fear responses.108,109,116 Balaban’s model 116 posits that vestibular input influences anxiety pathways through reciprocal projections between the PBN and vestibular nuclei, allowing for the integration of vestibular information in response to a perceived danger. 117 Thus, through this network, vestibular alterations might directly disrupt mechanisms underlying emotional regulation and, in patients who are predisposed, this might contribute to experience dissociation as a coping mechanism to deal with extreme anxiety, combining a state of increased alertness with an inhibition of the emotional response system. 118 Studies in patients with Post Traumatic Stress Disorder (PTSD) suggest that those with co-occurring DD symptoms have a distinct physiological profile, including bradycardia, increased prefrontal cortex and reduced amygdala activities—the opposite of PTSD patients without DD.119,120 In addition, PTSD with DD symptoms is associated with reduced functional connectivity between vestibular nuclei and cortical regions involved in self-perception.100,121 This pattern may reflect an adaptive survival response that reduces anxiety while increasing vigilance.
In conclusion, the findings of this review substantiate the idea that there is an association between the vestibular function and anxiety, and suggest that this association may exacerbate the severity of DD symptoms through specific neural pathways.
Neurofunctional models
The results of the present review seem to support the three-step model of Elyoseph and colleagues,
12
which integrates vestibular dysfunctions, spatial disorientation, anxiety and DD symptoms. According to this model, changes in the peripheral vestibular system, which primarily affect otolithic functions, can initially lead to spatial disorientation through their influence on the temporoparietal junction (TPJ) and hippocampal areas and increase anxiety levels via less defined neural pathways. According to the model, the interaction between spatial disorientation and anxiety contribute to the emergence of altered perceptions of the body and stimuli in the surrounding environment, experienced as DD symptoms. However, the findings of the present review provide important insights that need to be considered and integrated in Elyoseph’s model.
12
First, the results of the reviewed studies show that DD symptoms are not only associated with peripheral vestibular pathologies (otolith dysfunction) but are also linked to a broader range of vestibular alterations (see Table 3 & Figure 3). Second, in Elyoseph and colleagues (2023)
12
model, only TPJ and hippocampus are discussed in relation to the emergence of DD symptoms following vestibular alterations. However, as discussed in section 4.1, a wider network underpins vestibular processing, including areas such as the cingulate cortex, the precuneus, and the insula,
91
which are also implicated in DD.92,104,105,122 Finally, this model does not provide a clear explanation for the cognitive mechanisms by which DD symptoms would arise from the interaction between vestibular dysfunctions, spatial disorientation and anxiety. Graphical representation of the connection between each study, vestibular pathologies, and the presence of DD symptoms. Orange lines represent patients with DD symptoms and gray lines represent patients without DD symptoms. Colors coded the relative numerosity of patients within each vestibular pathology.
In relation to this last point, we propose that a possible theoretical framework in which Elyoseph’s model can find a suitable integration is that of the predictive coding (Figure 2). The predictive coding framework—positing that the brain continuously generates and updates models of body representation to predict sensory inputs—has been previously used to interpret DD symptoms.123,124 In line with this view, multisensory mismatch and perceptual incoherence have also been hypothesized to underlie self bodily alterations in patients with vestibular disorders. 125 According to the predictive coding framework, discrepancies between predicted and actual sensory inputs, known as prediction errors, prompt the brain to adjust its internal models to better align with reality. According to Saini and colleagues, 124 when interoceptive signals become incoherent and cannot be reconciled with input from the external environment, the prediction error dramatically increases. The organism would resolve this state of dissonance by silencing the bottom-up interoception leading to a scenario in which “the body is not anymore the physical medium through which the outside world is experienced. Consequently, the transparency that characterizes the phenomenological experience of being a self is now lacking, and will lead to phenomena of depersonalization.” 124 Still considering the loss of self-transparency as a central factor in the onset of DD symptoms, Ciaunica’s model (2022) 123 posits that, under normal conditions, individuals process bodily self-related information in background or “transparently.” On the contrary, in DD, pathological attention is directed toward bodily related information (e.g., interoception). This anomalous attention interferes with the normal self-processing, ultimately diminishing the transparency of the self and giving rise to DD symptoms as exampled in Ciaunica (2022) 123 : “In our example: over-attending to one’s leg movements while running may prompt people to detach themselves from the action, and see themselves from ‘above’.” (for a more detailed description of the mechanism, see 123). It is important to note that, in both models, the loss of a transparent self-processing is a crucial factor in the pathophysiology of DD. As we previously discussed, optimal self-processing requires bodily information to be efficiently processed in the background. When this information is either suppressed (as in Saini 124 ) or subjected to pathological attention that disrupts its natural, implicit processing (as in Ciaunica 123 ), the normal processing of bodily signals is compromised, ultimately leading to DD symptoms. However, both Saini’s and Ciaunica’s models do not explicitly include the vestibular system. Here, we propose an integration of Elyoseph’s model that aligns with the models of both Saini (2022) 124 and Ciauinca (2022), 123 and builds on Lopez and colleagues (2013) 125 account of multisensory mismatches underlying bodily self-disorders following vestibular alterations. When a vestibular dysfunction occurs, the brain’s expectations do not match the received vestibular signals, leading to prediction errors related to body orientation and movement. The inability to reconcile these errors would create a state of cognitive dissonance that would prompt the brain to down-weight vestibular signals in favor of other information related to bodily processing and movement that it deemed more reliable such as vision and interoception. These reweighting of sensory modalities may generate an imbalance towards specific bodily information (e.g., vision and interoception) that would interfere with their normal processing, disrupting the phenomenological transparency of the self and leading to DD symptoms as hypothesized by Ciaunica and colleagues (2022). 123 Interestingly, continuous experience of multisensory mismatch could lead to alterations in the internal models, thereby altering predictions about movement and body position. This may explain why patients suffering from chronic vestibular disorders manifest DD symptoms. Crucially, this sensory mismatch is inherently stressful and, depending on individual susceptibility, can trigger anxiety as the brain interprets the mismatch as a potential threat to physical stability and safety. 126 Following vestibular alterations, it is also possible that, when anxiety becomes overwhelming, it is mitigated through the downregulation of emotional responses, 127 leading to emotional numbing and thereby exacerbating the severity of DD symptoms. This hypothesis is supported by the evidence of vestibular system connections to regions involved in emotion regulation, stress response, motor control, and in the generation and updating of internal models of body position and orientation. 126
In conclusion, we here propose that spatial disorientation and anxiety may not be considered merely marginal symptoms associated with vestibular disorders but rather as intrinsic factors that can determine the intensity of DD symptoms. Based on the reviewed studies and theories, we propose a revision of Elyoseph’s model 12 in which vestibular dysfunction, by altering the activity of higher-order regions (e.g., TPJ, precuneus, and cingulate cortex) and the hippocampus, disrupts the brain’s ability to generate accurate predictions about bodily spatial representation and movement, leading to spatial disorientation. Such an impairment may prompt the brain to up-weight other sensory information over vestibular ones, generating DD experiences and, in individuals with psychological vulnerability, contributing to the development of anxiety. To cope with this anxiety, the brain may downregulate the fear response, producing emotional numbing. The combination of spatial disorientation and anxiety may, in turn, exacerbate the frequency and intensity of DD symptoms. Future research should systematically investigate this model, adopting a multidisciplinary approach that integrates neuroimaging, in-depth clinical evaluations, and behavioral assessments to further elucidate the complex mechanisms involved.
Clinical implications
The findings of this review hold several clinical and theoretical implications. One potential recommendation is to expand routine clinical assessment for patients with vestibular disorders to include evaluations of anxiety and DD symptoms. Enhancing our understanding of the causal relationship between vestibular dysfunction and the emergence of DD symptoms may inform the development of more effective and tailored treatment strategies. Currently, the most commonly employed interventions for DD symptoms include pharmacological approaches (e.g., antidepressants, antipsychotics, antiepileptics, and opioid inhibitors), psychotherapy, and non-invasive neuromodulation techniques. 128 While the first two approaches may prove beneficial due to the aforementioned association between DD symptoms and anxiety, the third one represents a novel avenue for the treatment of DD symptoms. Indeed, DD disorder has been associated with alterations in the activity of fronto-temporo-parietal areas 101 and stimulation techniques that target these areas appear to ameliorate DD symptomatology.128,129 For instance, a 3-week 1 Hz rTMS treatment (30 min per session at 100% of the resting motor threshold) over the right TPJ improved DD symptoms in 23 outpatients diagnosed with DD disorder. 130 It is noteworthy that vestibular stimulation has been found to affect the activity of areas that partially overlap with those altered in patients with DD.91,131,132 Random noise GVS, which add stochastic resonance to the peripheral vestibular system, 133 and left-ear CVS have been proved effective in rehabilitating visuospatial and body-representation disorders origination from TPJ lesions, such as neglect (for a review, see 34) and somatoparaphrenia. 33 For a detailed review on the clinical use of GVS see 134. These observations suggest that vestibular stimulation may prove beneficial in alleviating DD symptoms.
Limitations of current studies and future perspectives
The results of this review may help to improve our understanding of the vestibular system involvement in DD symptomatology. However, the majority of the discussed studies employed a cross-sectional design, posing limits to the possibility of addressing a causal relationship between vestibular disorders and DD symptoms. To this purpose, future research should investigate this relationship by using more controlled protocols such as RCTs. Furthermore, the integration of neuroimaging techniques could reveal new insights into the neurofunctional mechanisms of this relationship.
As for the correlated factors, both anxiety and spatial disorientation have been found to be correlated with DD symptoms in vestibular patients and in healthy individuals undergoing vestibular stimulation. However, they were assessed with different questionnaires and tasks, posing constraints to the possibility of comparisons across studies. Moreover, anxiety measured in healthy individuals following vestibular stimulations refers to episodic anxiety, which differs from the chronic anxiety experienced by patients with vestibular alterations. More consistency between assessment tools would allow a better comprehension of how anxiety and spatial disorientation contribute to shape DD symptoms in vestibular patients and in healthy individuals undergoing vestibular stimulations.
Finally, 20 out of 23 studies assessed DD symptoms via questionnaires, and the remaining 3 via qualitative reports. Future research should take into account behavioral symptoms of DD besides self-reporting. Indeed, by knowing how patients with DD disorder perform during specific experimental tasks, we could investigate whether vestibular patients or healthy individuals undergoing vestibular stimulation produce performances comparable to those of DD patients. For instance, there is evidence of self-face recognition deficit in patients with DD disorder.135,136 It might be of interest to investigate whether vestibular patients and healthy individuals after GVS/CVS display a similar pattern of behavioral responses. Moreover, patients with DD disorder show a specific pattern of physiological responses (i.e., reduced electrodermal activity to unpleasant stimuli).137,138 It may be of interest to investigate whether vestibular alterations lead to comparable changes. This approach integrates both the phenomenological and the behavioral counterpart of the relationship between vestibular alterations and DD symptoms, allowing us to grasp a more complete understanding of this relationship.
Conclusions
This systematic review aimed to analyze the existing evidence on the relationship between alterations in the vestibular input and the occurrence of DD symptoms. Based on the reviewed studies, both patients with vestibular disorders and healthy individuals exposed to artificial vestibular stimulation can manifest DD-like symptoms comparable to those observed in individuals diagnosed with DD disorders. Notably, within this relationship, anxiety and spatial disorientation often appear as co-occurring symptoms. Following vestibular changes, the interaction between these two symptoms could dysregulate the perception of self in the environment and lead to DD symptoms. Within the predictive coding framework, such vestibular alterations may prompt the brain to downregulate the vestibular input in favor of other body related information, altering their normal processing and leading to the emergence of DD symptoms. Crucially, this state of uncertainty can cause anxiety which in turn could trigger emotional numbing, a key feature of DD symptoms. Future research is necessary to clarify the mechanisms linking vestibular changes to DD symptoms. The results of this research will enhance our understanding of the neural underpinnings of self-consciousness and pave the way for more effective and targeted therapeutic interventions.
Footnotes
Acknowledgments
This article was produced while CZ was attending the PhD program in Space Science and Technology at the University of Trento, Cycle XXXIX, with the support of a scholarship financed by the Ministerial Decree no. 118 of 2nd march 2023, based on the NRRP - funded by the European Union - NextGenerationEU - Mission 4 “Education and Research,” Component 1 “Enhancement of the offer of educational services: from nurseries to universities” - Investment 4.1 “Extension of the number of research doctorates and innovative doctorates for public administration and cultural heritage.
ORCID iDs
Author Contributions
Samuel Cento: Writing—review and editing, writing—original draft, supervision, methodology, and conceptualization. Roberto Gammeri: Writing—review and editing, writing—original draft, supervision, methodology, and conceptualization. Claudio Zavattaro: Writing—review and editing, methodology, risk of bias assessment, and conceptualization. Emanuele Cirillo: Writing—review and editing. Hilary Serra: Writing—review and editing. Raffaella Ricci: Writing—review and editing, supervision, and conceptualization.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a MUR (Ministero dell’Università e della Ricerca) grant to RR (grant number: RICR_RILO_19_02).
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
