The dorsolateral prefrontal cortex as a potential target for electrical stimulation in the treatment of vestibular‐based nausea

Abstract

As a result of its location (facilitating ease of access) and its multimodal nature, the dorsolateral prefrontal cortex (dlPFC) is a commonly targeted site for transcranial electrical and magnetic stimulation in the treatment of psychiatric disorders. However, this cortical region has many interconnections throughout the brain, overlapping with other systems. One such example is the vestibular system. Starting at the vestibular organs within the inner ear, the vestibular system plays a major role in nauseogenic responses, and many vestibular disorders do not have well‐documented treatment plans. Given the overlapping circuitry between the dlPFC and vestibular processing networks, it has been hypothesised that the two would have interactions with one another when stimulated. Indeed, recent work has shown transcranial alternating current stimulation of the dlPFC to have an inhibitory action on sinusoidal galvanic vestibular stimulation‐induced nausea and perceptions of motion. Furthermore, stimulating the dlPFC through transcranial direct current stimulation has reduced dizziness in a cohort of phobic postural vertigo patients. This review aims to introduce the vestibular system and vestibular‐based nausea, including the cortical processing network, before discussing the dlPFC as a potential site for therapeutic targeting in various vestibular‐related disease states. This targeting focusses on transcranial stimulation, first in vestibular disorders, then in generalised motion sickness, concluding with speculation upon its possible (though perhaps less probable) ‘blue‐sky’ use in chemotherapy‐induced nausea and vomiting.

Abstract figure legend Recent work has shown transcranial electrical stimulation of the dorsolateral prefrontal cortex (dlPFC) to mitigate vestibular perceptions. Though definitive pathways require further elucidation, this interaction may be modulated by dlPFC inhibitory action on vestibular signalling in the insular cortex, thalamus and/or the nucleus of the solitary tract (NTS). If further research supports the dlPFC‐mediated suppression hypothesis, this work has the ability to translate to a wide range of clinical applications in vestibular‐ and nausea‐related ailments. Created with BioRender.com.

Introduction

The dorsolateral prefrontal cortex (dlPFC) is a multifunctional brain region, most known for its role in working memory performance (Barbey et al., 2013; Curtis & D'Esposito, 2003). However, because the dlPFC has extensive connections throughout the cortex, it is involved in all manner of functions from psychiatric disorders such as anxiety and major depressive disorder (Li et al., 2022; White et al., 2023) to executive function (Molavi et al., 2020; Panikratova et al., 2020). Importantly, recent work has also shown the dlPFC to exert inhibitory influences on vestibular‐related nausea (Lotze et al., 2025; McCarthy, Datta, et al., 2023a, 2025; Palm et al., 2019). This review aims to briefly highlight nausea in the context of the vestibular system (hence, with an emphasis on motion sickness) and discuss the cortical and subcortical regions involved in generating the nausea response. The dlPFC will then be introduced as a potential site to be targeted in the treatment of nausea and vestibular dysfunction, starting with vestibular disorders, before generalised motion sickness, and concluding with theoretical (and very much speculative at this stage) use in the treatment of chemotherapy‐induced nausea and vomiting.

The vestibular system and motion sickness

Before introducing motion sickness, it is important to briefly introduce the vestibular system, given the crucial role that it plays in this response. More in‐depth reviews on the vestibular system are provided by Day and Fitzpatrick (2005), Fife (2010) or McCarthy, Henderson, et al. (2023). Starting with the vestibular apparatuses located within the inner ear, the vestibular system encompasses several cortical and subcortical regions which work together to generate a human or animal's sense of balance (Hansson et al., 2010; Stephan et al., 2005). Simplistically put, vestibular hair cells within the vestibular apparatuses are bent with movement (Guth et al., 1998). The degree of gravitational and inertial accelerations in the linear plane is detected by the utricle and saccule, whereas the semi‐circular canals detect angular acceleration (Soyka et al., 2015). This information is sent towards the four (superior, inferior, lateral and medial) vestibular nuclei within the brainstem before being propagated to other regions including, but not limited to, the cerebellum, the parietal operculum, and the insular, somatosensory, prefrontal (including the dlPFC) and occipital cortices. Each region contributes to different aspects of vestibular processing (Barmack 2003; Brandt & Dieterich, 1999; Dieterich & Brandt, 2018; Frank & Greenlee, 2018), with many interconnections resulting in a rather complex system (discussed further below in the scction ‘Stimulation of the dlPFC’). It is for this reason that vestibular‐related maladies, such as motion sickness, still do not have conclusive results regarding their origin and cortical processing networks.

Nevertheless, motion sickness is known as a multifaceted response to both real and perceived motion, presenting with symptoms as diverse as cold sweating, facial pallor, sopite syndrome and, most commonly, nausea (Golding, 2016). In extreme circumstances, this may even lead to an emetic response (i.e. vomiting). As such, motion sickness and nausea in general can range from a mild inconvenience to a major debilitating factor. Despite its prevalence in society – especially so now, with advancements in virtual reality and importance in space travel – motion sickness remains an area of research that is not fully understood. There have been several different theories hypothesised throughout the years with respect to to the processing of motion sickness and nausea through the brain and why some people may experience it to a greater extent than others, but, undoubtedly, a key aspect of this response is the vestibular system, as discussed below.

Motion sickness susceptibility

The level of susceptibility to motion sickness has been approached from multiple perspectives, suggesting all manner of variables, from age to a cyclical pattern with gender, and even to spinal cord injury (Grunfeld & Gresty, 1998; Lamb & Kwok, 2015; Macefield & Walton, 2015). In general, motion sickness susceptibility peaks in childhood with a gradual decline during adolescence and adulthood, and females are reported to experience motion sickness to a greater extent than males (though even this is somewhat disputed (Cha et al., 2021)). However, because of the vast array of factors that may or may not influence susceptibility (Golding, 2006), this field is an ever‐expanding one. Even treatments used to counteract susceptibility, of which there are many, do not have guaranteed success and are not without other constraints. Pharmacological treatments, for example, are known to induce drowsiness and impaired cognitive performance (Weerts et al., 2014), which is especially critical for pilots, military personnel and similar roles. Moreover, behavioural treatments, such as habituation to the stimulus, can be time‐consuming as a result of repeated sessions and are restrictive to the specific type of stimuli, resulting in a lack of generalisation (Kaufman, 2005; Ressiot et al., 2013).

Hypotheses for the origin of motion sickness

Although the exact mechanisms behind the susceptibility of an individual to motion sickness remain unresolved, the most common explanation for motion sickness stems from sensory conflict (Yates et al., 1998). This can take place within the vestibular apparatus alone with: (i) mismatch between inputs from the semi‐circular canals and otolith organs; (ii) mismatch between a sensed and actual gravitational upright; and/or (iii) a multisensory mismatch in which the sensory input perceived differs from the input expected through past experience (Cha et al., 2021). It is for this latter reason that motion sickness is considered to be subject to habituation: when the unexpected input becomes expected through exposure, the prevalence of motion sickness will begin to abate (Wood et al., 1994).

Given that the primary role of the vestibular apparatus is to detect changes in head acceleration in space, it also serves as the first point of contact in the motion sickness pathway. Indeed, stimulation of the otolithic organs is capable of inducing nausea (Ventre‐Dominey et al., 2008). These factors emphasise the intrinsic involvement of the vestibular system in the processing of motion sickness and its associated nausea. For example, when visual cues determine that large movements are occurring in the external environment, and yet vestibular cues indicate that there are little to no actual head movements, sensory conflict occurs – initiating a motion sickness response (Yardley, 1990). Interestingly, however, vestibular sensory conflict does not necessarily need a visual component for motion sickness to take place. Individuals presenting with blindness, whether it be congenital, late‐acquired or induced for the sake of experimentation, show comparable levels of susceptibility to sighted individuals (Graybiel, 1970). For reasons such as this, it was considered that visceral graviceptors – receptors which detect acceleration by abdominal viscera and which contribute in large part to the detection of bodily position in space – may also play a largely deterministic role in sensory mismatch (Mittelstaedt, 1996; von Gierke & Parker, 1993). However, the involvement of graviceptors in this response is somewhat contentious. A more widely accepted view on sensory mismatch can be further seen in research describing the velocity storage network. Although this network will be elaborated upon in the section below, briefly: angular velocity is typically ‘stored’ in this model and eye movement is altered accordingly, with mismatches between these systems resulting in motion sickness. As such, Laurens and Angelaki (2011) have argued that the velocity storage phenomenon is itself a multisensory integration process. Furthermore, baseline sensitivity to visual–vestibular conflict would also seem to play an important role in determining an individual's motion sickness response, as Halow et al. (2022) have shown with their work in virtual reality, or ‘cyber sickness’, comprising a field of research that is becoming increasingly relevant. Each of these examples serve to showcase the breadth of the just one hypothesis for the origin of motion sickness, highlighting the complexity of the field.

Several other explanations for motion sickness have been suggested, one of which is the toxin detector hypothesis. It states that the vestibular system is capable of detecting unusual sensory input patterns and identifying them as malfunctions, which subsequently triggers an emetic response (Golding, 2016; Money & Cheung, 1983). This comes about through the vomit initiation response after the body detects possible neurotoxin ingestion and is, ostensibly, an accidental by‐product of an ancient evolutionary response. Similarly, the disorientation/motor warning hypothesis suggests that motion sickness is an evolutionary response to encourage avoidant behaviour of situations that compromise spatial perception and motor stability (Guedry et al., 1998). An alternative explanation lies in the evolutionary maladaptation hypothesis. This hypothesis states that motion sickness simply comes about through the proximity of the vestibular system and vomiting circuitry in the brainstem, in other words: by accident (Golding, 2016). This list of theories is by no means exhaustive [more in‐depth reviews on this specific aspect of motion sickness are provided by Cha et al. (2021) and Golding (2016)] but serves to highlight the diversity in the field. The limitations in each of these hypotheses are the reason why motion sickness research remains inconclusive and emphasises the need for further research.

Cortical and subcortical processing

Several brain locations involved in the processing of motion sickness, on the other hand, have been extensively studied in recent years and have produced less ambiguous results. With this being said, a common pathway for nausea and vomiting is still yet to be clearly defined. Nevertheless, key structures in this pathway include the dorsal vagal complex [encompassing the nucleus of the solitary tract (NTS), area postrema and dorsal motor nucleus of the vagus nerve (DMX)], cerebellum, visual, cingulate and insula cortices, and many more (Fig. 1) (Cohen et al., 2019; Napadow et al., 2013; Varangot‐Reille et al., 2023; Zhong et al., 2021). The next section aims to give but a brief introduction to a few of the important cortical and subcortical regions involved in motion sickness – to cover the entire topic would require a separate review all of its own.

Figure 1. Key structures in the neural circuitry of nausea and vomiting.

Cortical and subcortical regions involved in the processing of nausea and vomiting are depicted. The complex interconnections between regions contributes in large part to the uncertainties in the field. Regions shown in blue are deep structures and can be located on the depicted brain slice. Regions shown in yellow are located more superficially to the brain slice in the diagram. The location of regions are approximations and slightly resized for clarity. ACC, anterior cingulate cortex; AP, area postrema; dlPFC, dorsolateral prefrontal cortex; DMX, dorsal motor nucleus of the vagus nerve; IFG, inferior frontal gyrus; NTS, nucleus of the solitary tract; PCC, posterior cingulate cortex; PIVC, parieto‐insular vestibular cortex; SII, secondary somatosensory cortex; vmPFC, ventromedial prefrontal cortex. Created with BioRender.com.

Although motion sickness will only lead to emesis in rare cases, it was once considered that the emetic response in motion sickness involved a chemoreceptive trigger zone in the area postrema situated within the dorsal medulla. This area lacks a distinct blood–brain barrier, which allows it to respond to toxins in the blood and trigger a non‐motion related emetic pathway (Borison, 1989). Indeed, lesions encompassing the area postrema can prevent vomiting, as shown through studies involving several emetic drugs (Miller & Leslie, 1994). However, more recent brain lesion studies have demonstrated that these effects may be a consequence of the lesions encompassing the immediately adjacent NTS, at least with regards to motion sickness (Yates et al., 2014). There has been a shift away from implication of the area postrema and it is now thought that, rather than the chemoreceptive trigger zone, it is the NTS or DMX that play major roles in the emetic response to motion sickness (Beh, 2021; Wickham, 2020; Zhong et al., 2021). The NTS is the recipient of area postrema efferents and visceral afferents and also receives direct projections from vestibular nuclei, placing it in a prime position to integrate emetic signals (Fig. 1). Additionally, the DMX receives information from the NTS as well as several other brain regions and itself has projections toward the gut, with studies demonstrating its influence on gastric motility (Berthoud et al., 1991; Hyland et al., 2001). Moreover, in a study conducted by Chen et al. (2018), the effects of histamine in the dorsal vagal complex were explored in relation to motion sickness. It was found that the expression of histamine N‐methyltransferase in this complex had an inverse relationship with the development of motion sickness and the resulting emesis. This serves as merely one example of the pharmacological basis of the brainstem contributions to motion sickness. A more comprehensive review on the topic is provided by Zhong et al. (2021).

Furthermore, it is also important to note the involvement of the velocity storage network, primarily situated within the brainstem as well. As Cohen et al. (2019) describe, this network comprises of a ‘velocity storage integrator’ and a ‘velocity storage time constant’ tightly moderated by the ‘vestibular‐only’ neurons located within the vestibular nuclei. As their name suggests, these neurons have been shown to have connectivity to the vestibular system, but not directly to motor control of the eye muscles (Büttner et al., 1991). Angular acceleration input from the hair cells within the semi‐circular canals is detected by the integrator and then ‘stored’ as an angular velocity signal. The integrator is then shown to hold the eye rotation axis steady with regards to the gravitational and spatial vertical (Raphan et al., 1981), offsetting the reaction of visual mismatch and diminishing the motion sickness response by way of the velocity time constant. Individuals with a high baseline time constant are more susceptible to motion sickness (Clément & Reschke, 2018) and, as such, when time constants are reduced through habituation, motion sickness is likewise reduced (Dai et al., 2003). The integrator itself has been shown to have robust inhibitory connections with the nodulus of the cerebellum (Meng et al., 2014). Indeed, lesion studies of the nodulus have demonstrated loss of eye movement adaptation (Cohen et al., 1992), leading to a regression back to motion sickness after habituation. Velocity storage has only been described in brief detail here and a more in‐depth review on the different representations of the phenomenon is provided by MacNeilage et al. (2008).

The above shows an example of how the cerebellum is implicated in vestibular‐based nausea and, indeed, it is a region of vital importance. Cerebellar interactions with the vestibular system (which would later be dubbed the ‘vestibulocerebellum’) were first noted by Bard and Woolsey (1947) in their study on motion sickness in dogs. Ablation of the cerebellum (specifically the pyramis, uvula and nodulus) prevented vomiting as a result of the motion of a swing but did not alter vomiting reactions to spoiled food or emetic drugs. The vestibulocerebellum has subsequently been explored in depth, with many robust connections established between the cerebellum and vestibular nuclei (Barmack & Yakhnitsa, 2021; McCarthy, Henderson, et al., 2023).

Motion sickness, however, is not restricted to subcortical regions. With regards to the visual cortices, functional magnetic resonance imaging (fMRI) has revealed that the primary visual cortex (V1) and middle temporal cortex (V5) are activated with motion sickness induced by a visual stimulus (Napadow et al., 2013). However, Napadow et al. (2013) report that, because of the lack of activation with increasing nausea in other visual cortical areas and the vestibular nuclei, it would appear that V1 and V5 are coupled to nausea perception rather than a visual/vestibular mismatch. In addition to these findings, Napadow et al. (2013) found activation with increasing nausea perception in areas such as the insula, the cingulate cortex and the dlPFC. Results such as these are corroborated by other studies noting that these areas contribute towards interoception and cognition (Cieslik et al., 2013; Ernst et al., 2014), both of which are important for nausea as it is regarded as a subjective experience (Varangot‐Reille et al., 2023). When expanding upon their earlier study above, Toschi et al. (2017) went on to examine V1 and V5 in relation to the anterior insula and mid‐cingulate cortices. The peak nausea state of participants displayed a reduction in connectivity between the left and right V1 compared to baseline, which was negatively correlated with the motion sickness susceptibility questionnaire (Golding, 1998) scores of each participant; that is, participants who were more susceptible to motion sickness showed a greater reduction in connectivity. By contrast, connectivity between right V5 and the anterior insula, as well as between left V5 and the mid‐cingulate cortex, was found to increase during peak nausea. From these results, it was suggested that visual/vestibular mismatch information transfer may indeed be regulated by these regions after all, with the increased connectivity between brain regions associated with nausea and visual motion processing.

Stimulation of the dlPFC

Having established a basis for vestibular‐related nausea, we can now pivot towards clinical representation of the issue and a potential new treatment for it. As briefly mentioned above, activity within the dlPFC is known to correlate with nausea (Napadow et al., 2013). Given that the dlPFC is also known to have robust connections with the insula (Fu et al., 2021; Yuan et al., 2020), we recently sought to investigate whether the dlPFC has interactions with perceptual responses generated by the vestibular system (McCarthy, Datta, et al., 2023). In finding that the perceptions of sway and nausea induced by slow sinusoidal galvanic vestibular stimulation (sGVS) were significantly abated with concurrent transcranial alternating current stimulation (tACS) of the dlPFC, the work was then extended into fMRI (McCarthy et al., 2025). Using blood‐oxygen‐level‐dependent (BOLD) imaging, the findings suggested that the insula/parietal operculum, thalamus and/or NTS may be key structures involved in this apparent dlPFC‐mediated inhibition of the vestibular system. By extrapolating these results, this interaction between the two systems provides an exciting new avenue for potential targeted treatment.

Before exploring this notion, though, it is important to note the work by Lotze et al. (2025). They, too, support the idea of a dlPFC‐mediated top‐down inhibition of the vestibular system. Given that anxiety correlates with vestibular disorders (Bigelow et al., 2016; Lahmann et al., 2015), they designed a study in which sGVS was applied to healthy participants, as was a fear‐conditioning stimulus. Through this and BOLD fMRI, they were able to find considerable overlap in cortical activation between the stimuli. This analysis highlighted the prefrontal cortex, including the dlPFC, as previously observed in a meta‐analytical review on vestibular stimulation and fear learning (Neumann et al., 2023). That review, much like our previous work (McCarthy, Datta, et al., 2023a, 2025), indicated that the dlPFC was capable of acting through the posterior insula to suppress unwanted vestibular‐related effects. However, this conclusion focussed on emotion and anxiety processing, rather than direct application of stimuli to the dlPFC. Palm et al. (2019), following the same reasoning that the dlPFC and vestibular system interact through emotional processing, showed in their open label pilot study that transcranial direct current stimulation (tDCS) of the dlPFC was effective in reducing dizziness in phobic postural vertigo patients. Despite Palm et al. (2019) and our study (McCarthy et al. 2025) approaching dlPFC‐mediated vestibular function from different perspectives, they both reached the same conclusion: that the dlPFC could prove effective as a site for treatment of vestibular disorders.

Although more research is required to verify any mechanistic pathways, we are able to make early speculations upon how this interaction may be taking place. Stimulation of the dlPFC could promote inhibitory action (e.g. via the inhibitory neurotransmitter GABA) on histamine or ACh receptors, or even voltage‐gated ion channels, just as current medications to treat vestibular disorders do (Soto & Vega, 2010). Bunai et al. (2021) suggest that tDCS of the dlPFC promotes GABA release in the ipsilateral striatum. Given the connections between the caudate nucleus (a subset of the striatum) and vestibular function (Stiles & Smith, 2015), this hypothesis may have some merit. If such is the case, then the dlPFC may be able to inhibit the vestibular signalling cascade – preventing vestibular information from being properly processed. As discussed in McCarthy et al. (2025), altered BOLD signal‐intensity between transcranial electrical stimulation of the vestibular apparatuses, dlPFC and both sites concurrently, suggests that vestibular information processing may be stopped at the insular cortex, thalamus and/or the NTS. With (i) a suggested reciprocal feedback loop between the dlPFC and parietal operculum (Selemon & Goldman‐Rakic, 1988); (ii) direct dlPFC connections with the thalamus (Le Reste et al., 2016; Zikopolous & Barbas, 2007); and (iii) possibly indirect dlPFC connections with the NTS (perhaps via way of the insula or thalamus) (Levinson et al., 2023; Macefield & Henderson, 2020), GABAergic dlPFC influences have many possible ways of interfering with vestibular processing.

It is important to compare here, however, the types of stimuli used in our previous work (McCarthy, Datta, et al., 2023a, 2025) and Palm et al. (2019) (Table 1). In our study (McCarthy, Datta, et al. 2023), we used slow tACS (±2 mA, 0.08 Hz) to mimic the sGVS parameters previously shown to have the greatest nauseogenic response (Javaid et al., 2019; Klingberg et al., 2015). The mitigation of these responses was observed in stimulating both the left and right dlPFC. Given this finding, the right dlPFC was arbitrarily chosen for stimulation (±2 mA, 0.2 Hz) in the study by McCarthy et al. (2025). However, Palm et al. (2019) mitigated vestibular disorder by applying a direct current (anodal 2 mA) to the left dlPFC. Given these results, the parameters of stimulation seem somewhat flexible. Therefore, any future studies into this relationship would benefit from exploring stimulation optimisation. Although symptoms were reduced in Palm et al. (2019) and McCarthy, Datta, et al. (2023), they were not eradicated. The current intensity of (±) 2 mA chosen in each study is generally effective and well tolerated by participants, but it may very well be that higher or lower intensities will produce differing results. Indeed, this could be optimised on a case‐by‐case basis depending on biological variability (pain tolerance, scalp thickness, disorder severity, etc.), perhaps incorporating a closed‐loop circuit for real‐time adaptation of stimulation parameters based on biological feedback (Wansbrough et al., 2024). The same may be said for stimulation frequency and duration. Fortunately, the implementation of tACS and tDCS, and the changing of their stimulation parameters, is a simple task (as discussed further below) and so this individualisation is not a limitation. The three studies discussed here may lay some groundwork, but that is not to say that the parameters used were the most optimal.

Table 1.

Studies investigating prefrontal cortex influences on the vestibular system

Reference	Population	Sample size	Stimulation type	Number of sessions	Targeted hemisphere	Outcome measures
Palm et al. (2019)	Phobic postural vertigo patients (age 24–59 years, mean 45.6 ± 12.3)	8	tDCS (2 mA; 30 min; 15 s fade‐in/fade‐out)	5	Left dlPFC	Mitigation of dizziness
McCarthy, Datta, et al. (2023a)	Healthy adults (age 21–32 years, mean 23.3 ± 2.8)	23	tACS (±2 mA; 0.08 Hz; 100 cycles)	1	Left and right dlPFC	Mitigation of sGVS‐induced perceptions of movement and nausea
McCarthy et al. (2025)	Healthy adults (age 19–39 years, mean 26.6 ± 5.4)	20	tACS (±2 mA; 0.2 Hz; 60 cycles)	1	Right dlPFC	Mitigation of sGVS‐induced perceptions of movement and nausea with concurrent fMRI
Lotze et al. (2025)	Healthy adults (age range unspecified, mean 23.5 ± 4.2)	28	Pneumatic tactile stimulation of the left index finger	1	N/A	Identification of cortical structures involved in both anxiety and vestibular information processing

Note: The four studies comprising the field of prefrontal cortex stimulation (direct and indirect) to target overlaps with vestibular information processing are summarised.

Abbreviations: dlPFC, dorsolateral prefrontal cortex; fMRI, functional magnetic resonance imaging; sGVS, sinusoidal galvanic vestibular stimulation; tACS, transcranial alternating current stimulation; tDCS, transcranial direct current stimulation.

The key studies performed to date have been critically appraised and are summarised in Table 1. Indeed, as Table 1 highlights, this field of research is still in its infancy. Although the transcranial electrical stimulation studies discussed here display promising early proof of concept, they are relatively small in size and lack sham stimuli. As such, both participant and investigator are not blinded to the stimulation, allowing for factors such as placebo and bias to affect the interpretation of the results. However, true blinding to a transcranial electrical stimulation protocol proves challenging because most participants can feel the electrical stimulation as a slight ‘burning’ or ‘tingling’ sensation on their scalp. Therefore, control stimulation areas can be employed, but they too will not be a true sham stimulation for the same reason. These points, alongside the small sample sizes, limit generalisability, with too many extraneous factors playing a role. Further research is required with larger controlled trials to cover a greater range of biological variability, and further standardisation of the tACS/tDCS methods could aid in addressing their limitations. This includes standardisation of the application for the limits on depth of cortical stimulation and focality. As a result of the very nature of transcranial electrical stimulation, weak electrical currents delivered will dissipate through the scalp and the skull before reaching the brain tissue, let alone penetrate to deeper cortical regions (Vöröslakos et al., 2018). Furthermore, the large surface electrodes are incapable of precise cortical targeting (Nitsche et al., 2008), which may impact the individualisation of any potential treatment protocols. These factors and more must be considered in any future applications of the methods discussed herein.

Implications for practice

Vestibular dysfunction

From vestibular migraine to persistent postural‐perceptual dizziness to vestibular neuritis and many more, a plethora of vestibular disorders exist with varying levels of prevalence (Agrawal et al., 2013; Hülse et al., 2019). Although not as common and hence not as well‐known as other disorders, the impact of vestibular disorders on the lives of those afflicted cannot be understated. A substantial proportion of patients have been shown to indicate an inability to work, disruptions to their familial and social lives and cognitive impairment amongst other challenges (Bronstein et al., 2010; Chari et al., 2022). This also presents as a growing concern because vestibular dysfunction is far more pervasive in the elderly (Iwasaki & Yamasoba, 2015), which is something worth considering with the world's ageing population. As it stands, some specific disorders have well‐documented treatment plans, yet the effectiveness of the treatment is notably variable and still other disorders are poorly understood (Strupp et al., 2020).

The tACS of the dlPFC presented in our previous studies (McCarthy, Datta, et al., 2023a, 2025), or the tDCS of Palm et al. (2019), may prove translatable as alternative treatments for vestibular disorders – stopping the processing of ‘incorrect’ vestibular signalling that leads to the symptoms of the disorders. In this way, it can be thought to work similarly to the receptor antagonist medications that are the current primary treatment options (Soto & Vega, 2010). However, an important caveat is that, in each of the transcranial electrical stimulation studies discussed thus far (McCarthy, Datta, et al., 2023a, 2025; Palm et al., 2019), participants were seated or lying down. Although participant‐reported perceived sway (and lack thereof) was recorded with a linear potentiometer in McCarthy, Datta, et al. (2023), whether actual balance responses (as opposed to perceived) were mitigated with dlPFC stimulation was not directly assessed. As has been studied before, galvanic vestibular stimulation in standing subjects leads to postural sway (Wardman et al., 2003) and there is the possibility that concurrent dlPFC stimulation may remove the perception of sway, whereas participants still exhibit postural instability. If so, the utility and generalisability of the technique in treating vestibular disorders may be undermined. With that being said, should tACS or tDCS of the dlPFC prove to be effective on vestibular disorders, even if only for a few, it could have profound effects on improving patients’ quality of life, especially for drug‐resistant disorders.

This idea is further substantiated by the ease with which tACS of the dlPFC can be implemented. Locating and stimulating the dlPFC is by no means difficult, with it being a large and easily accessible frontal area of the brain. All that is required are simple surface electrodes and a stimulating device. Indeed, this very concept is already in use as an alternative at‐home treatment for depression and can be conducted with remote supervision (via telehealth or the like) for additional safety and support (Alonzo et al., 2019; Charvet et al., 2023). Through this method, small portable handheld devices are used to deliver tDCS to the dlPFC, stimulating the area to modulate cortical excitability and working to offset the changes which accompany the malady (Fig. 2) (Nitche et al., 2009; Shaw et al., 2017), comprising the same stimulation treatment used by Palm et al. (2019) on phobic postural vertigo. With only minor adjustments to optimise current intensity and waveform, this depression treatment strategy has the potential to be used for the clinical treatment of vestibular‐related disease states or, in a broader sense, for the more common motion sickness response. Given the safe and straightforward nature of its implementation, even if the dlPFC stimulation does not produce any cumulative habituation over time to counteract the vestibular effects (essentially ‘curing’ the problem), it may still prove useful for short‐term preventative measures. In doing so, it may be considered somewhat similar to the way in which paracetamol is used for short‐term pain relief – safe and effective, with use on an as‐needed basis.

Figure 2. Home‐based transcranial direct current stimulation of the dorsolateral prefrontal cortex.

An example of a typical at‐home transcranial direct current stimulation (tDCS) device is shown. These devices deliver electrical current through cables to surface electrodes placed on the left and right dorsolateral prefrontal cortex (dlPFC). The anode is placed on the left dlPFC in the diagram because this is the site used for depression treatment. The dlPFC can be easily stimulated with the large surface electrodes and localisation can be further facilitated with the help of a treating practitioner through telehealth. Created with BioRender.com.

This approach could be regarded as especially helpful for people who suffer from motion sickness as a direct result of their occupation. Motion sickness is far more common than vestibular disorders, with an estimated prevalence peaking in childhood at 35–43%, but remaining a significant problem in 14% of young adults (Cha et al., 2021). An epidemiological study of 70 million people, on the other hand, has shown vestibular disorders (including unspecific vertigo, vestibular neuritis and Meniere's disease) to present in 6.5% of people, with a skew towards the older age range (Hülse et al., 2019). To many, motion sickness may only be a minor discomfort which can be remedied with avoidant behaviour, although this is often to the compromise of efficiency. Though the methods discussed here might prove useful in these situations, they could also be used in more extreme and unavoidable situations too. Many transport‐based occupations come with an inherent risk of inducing motion sickness, whether that be on land (e.g. truck drivers), on the sea (e.g. captains of ships), in the air (e.g. pilots of aircraft) or even in space travel (Ortega et al., 2019; Reschke et al., 1998), with the latter being a consideration that is rapidly becoming more and more relevant. As mentioned earlier in this review, pharmacological treatments are available to offset the sickness, but their efficacy is variable and can induce drowsiness and reduced cognitive performance (Paul et al., 2005; Weerts et al., 2014). With technical nuance and the operation of heavy machinery, many of these jobs require strict vigilance to ensure the well‐being not only of the afflicted person in question, but also those around them. As such, the side‐effects of the drugs can be almost as problematic as the sickness itself. This is where dlPFC stimulation as a treatment differs from the medications: it lacks this drawback. Rather the opposite, it has been shown to actively enhance task‐based cognition (Lehr et al., 2019; Meiron & Lavidor, 2014). Therefore, this technique has the potential for a two‐fold beneficial effect: primarily to stop the motion sickness response, but also perhaps providing an additional attention‐ and response‐based side‐effect.

Chemotherapy‐induced nausea and vomiting

Finally, in more of a stretch to determine the extent to which the dlPFC can inhibit nausea, it would be particularly interesting to observe its effects on cancer chemotherapy‐induced nausea and vomiting. It is crucial to preface this section, however, with a note that the following is highly speculative and takes more of a ‘blue‐sky’ approach. Although there seems to be some circumstantial evidence that transcranial electrical stimulation and the dlPFC may be effective here, the infancy of the field necessitates much more in‐depth work to verify any of these claims. The following section merely aims to act as a vehicle to stimulate thought on the further use of transcranial electrical stimulation and the dlPFC as a target.

With that being said, chemotherapy‐induced nausea and vomiting is an aspect of cancer treatment that can be overlooked, given that it is a somewhat unavoidable side effect of a lifesaving treatment plan. Nevertheless, it has been shown to have profound impacts on the quality of life of afflicted patients, as evidenced by the ‘functional living index – emesis’ questionnaire (Lindley et al., 1992; Sommariva et al., 2016). Indeed, the vomiting itself can affect up to 40% of people undergoing chemotherapy, with the prevalence of nausea higher than even that (Ballatori et al., 2007; Gupta et al., 2021; Wickham, 2020). Prevalence does rely on several factors, however, including age, sex and the type of chemotherapeutic agent being used, with expert consensus grouping agents into four classes based on their intrinsic emetogenicity: minimal risk (<10%), low risk (10–30%), moderate risk (31–90%) and high risk (>90%) (Hesketh, 2008; Roila et al., 2006). This form of nausea is, admittedly, not directly related to any vestibular influences. However, the cortical emetic pathway related to these two types of nausea shares some common regions, namely: the NTS and DMX (Zhong et al., 2021). The primary means by which chemotherapeutic agents can induce the emetic response is considered to be through the enterochromaffin cells of the small intestine which release serotonin (Hesketh, 2008). Signals are then sent via vagal afferent nerves from these cells to the NTS, which acts as a hub for further signalling to induce nausea and vomiting (Ullah & Ayaz, 2023). The NTS also receives input from the vestibular nuclei to initiate the same response, and our work (McCarthy et al., 2025) has shown dlPFC connections to the NTS. Moreover, one participant in our previous study (McCarthy, Datta, et al., 2023) had an emetic response as a direct result of the nausea produced by the low‐frequency sGVS protocol. This same participant also reported no nausea sensations, let alone the feeling of wanting to vomit, when the vestibular apparatuses and dlPFC were stimulated concurrently. In this example, the dlPFC can be seen to perhaps have anti‐emetic properties, but one example is by no means conclusive. Furthermore, this stimulation is perhaps not as probable to play a role in chemotherapy‐induced nausea and vomiting as it is in the aforementioned vestibular dysfunctions. However, the capacity for dlPFC stimulation to be further applied to chemotherapy patients remains to be assessed and presents as an exciting prospect. Even in the event that it proves ineffective, the weak stimulation is highly tolerable and would probably not inconvenience the patients.

The concept of using dlPFC stimulation on a cancer chemotherapy patient group is not exclusive to potential use in the treatment of nausea and vomiting. This idea can further extend to post‐chemotherapy. Although necessary for treatment, it is well established that the drugs used in chemotherapy can have lasting neurotoxic effects, with chemotherapy‐induced peripheral neuropathy present in ∼68% of patients 1 month after chemotherapy (Banach et al., 2017; Seretny et al., 2014; Wang et al., 2021). Interestingly, these effects can sometimes manifest in the form of postural instability. Through this, a bridge is provided between both the vestibular dysfunction and the chemotherapy patients as described above. In their meta‐analytical review, Wang et al. (2021) have stated that studies investigating this postural instability primarily attribute the dysfunction to poor somatosensory feedback. However, they also make note of the fact that most of the studies lack robust testing of the vestibular system, so the extent to which it may be playing a part remains unclear. Indeed, Prayuenyong et al. (2018), in their own meta‐analysis, conclude that evidence for vestibular toxicities stemming from platinum‐based chemotherapy does exist, but the field is still somewhat inconclusive and in need of further research. Additionally, Wampler et al. (2007) attribute, in part, the postural instability seen in their cohort of women with breast cancer to vestibular malfunction. With this in mind, another avenue for dlPFC stimulation as a treatment method may present itself. The postural instability reported in these patients presents somewhat similarly to the aforementioned vestibular disorders and, as such, may be treatable with dlPFC stimulation in much the same way. This is not to say, however, that this is the only possible treatment option because physical training, for example, has been shown to reduce postural symptoms (Brayall et al., 2018; Yeasmin & Azharuddin, 2024). Furthermore, the use of tACS is by no means a panacea, merely a prospect or perhaps an adjuvant to other treatments. Nevertheless, tACS has the potential to reduce the instability by preventing the processing of ‘incorrect’ vestibular signalling that leads to the postural problems (again, possibly through GABAergic pathways (Bunai et al., 2021) centred on the insula/parietal operculum, thalamus or NTS (McCarthy et al., 2025)), but of course more research into the potential role of the vestibular system here is needed too.

Conclusions

Although nausea has been extensively researched throughout the years, because of its complex nature, many unknowns remain. Importantly, this extends to treatment. What is known, however, is that the vestibular system is integral to the motion sickness response and many other nausea‐related disease states. Given the shared cortical processing networks between the vestibular system and the dlPFC, and the fact that the dlPFC is already commonly targeted as a site for transcranial electrical stimulation in treating psychiatric disorders, this review has presented the dlPFC as a site for further treatment of nausea. This ranges from potential use in generalised motion sickness, to mitigating more specific pathological vestibular dysfunction and even to chemotherapy‐induced nausea and vomiting. Although such a treatment method would be simple to implement, whether or not it is actually effective in these conditions remains to be seen. Much research needs to be carried out aiming to evaluate the viability of this idea and optimising the stimulation technique and methods, perhaps on a case‐by‐case basis: indeed, it may be that the frequency of tACS may need to be adjusted in each individual to optimise symptom reduction. Nevertheless, should it prove effective, tACS of the dlPFC for the treatment of nausea has the potential to be life‐changing for patients with diseases that still do not have concrete treatment plans, as well as otherwise healthy people suffering from motion sickness.

Additional information

Competing interests

The authors declare that they have no competing interests.

Author contributions

B.M., E.J.H. and V.G.M. were responsible for conceptualisation. B.M. was responsible for writing the original draft. B.M., E.J.H. and V.G.M. were responsible for reviewing and editing. E.J.H. and V.G.M. were responsible for supervision

Funding

This work did not receive any funding.

Supporting information

Peer Review History

Biography

Brendan McCarthy is a postdoctoral research fellow at the Baker Heart and Diabetes Institute, having completed his PhD in 2024 through the Baker Department of Cardiometabolic Health at the University of Melbourne. His work has focused on non‐invasive electrical brain stimulation of the vestibular apparatuses and dorsolateral prefrontal cortex (dlPFC). Through this, he has worked to interrogate the networks associated with the human sympathetic connectome and cortical modulation of muscle sympathetic nerve activity. Brendan's research further extends into how the dlPFC may interact with the vestibular system to suppress motion‐induced nausea and the vestibulosympathetic reflexes.