Infrasound in Biology and Medicine: Insights into Mechanisms, Health Outcomes and Research Perspectives - A Narrative Review

Abstract

The study of infrasound represents an underexplored domain with profound implications for human health and operational readiness, particularly within civil, defence and security settings. Human exposure to these frequencies is on the rise due to both natural and anthropogenic factors, such as occupational conditions, wind farms, warfare tactics and transportation. This review critically examines the dualistic nature of infrasound by consolidating the current evidence based on qualitative exposure-effect pattern, pathophysiological signatures across animal models and controlled human experiments. By synthesizing current scientific literature, this article highlights the observed effects of infrasound on human well-being, while identifying key research gaps in mechanistic understanding. Moreover, this review underscores the necessity for systematic research aimed at elucidating the cellular and systematic pathways underlying infrasound-induced physiological complexities, and advocates for the development of a robust real-time bio-surveillance system tailored to monitor the exposure related-health outcomes. Additionally, recent technological advancements are explored, with a forward-looking perspective on its integration into next-generation diagnostic modalities and non-invasive therapeutic interventions. By integrating insights from both defence and health perspectives, the review emphasizes on the need to acknowledge infrasound as both a potential health hazard and a promising therapeutic modality, thereby shaping future directions in scientific research, healthcare policy and protective countermeasure development.

KEY MESSAGES

• (1)Infrasound exposure influences multiple physiological systems, including cardiovascular, vestibular and neural pathways.
• (2)Health outcomes depend on frequency, intensity and duration (time) of exposure, underscoring the need for well-defined exposure thresholds.
• (3)Civil and Defence sectors are particularly impacted, where infrasound is both a potential hazard and a tool for surveillance, monitoring and communication.
• (4)Emerging therapeutic applications suggest that controlled infrasound may offer novel strategies in wound healing and pain management.
• (5)Future research must bridge biomedical and civil perspectives to establish biomarkers, protective measures and translational pathways for safe and beneficial use of infrasound.

INTRODUCTION

Infrasound refers to sound waves with frequencies below the threshold of human hearing (<20 Hz).[1] These waves have gained significant attention owing to their bizarre interactions with biological systems. Directed energy sources have emerged as a useful modality for multifarious applications as a result of technological advances in the civilian, military, aerospace and health care domains. Some examples of directed energy sources are high-intensity lasers, radiofrequency, microwaves and infrasound. The non-kinetic potential of Directed Energy Weapons (DEWs) makes them a potent and less expensive weaponry platform with unconstrained firing power as compared to conventional weaponry systems for deployment to counter military aircraft, unarmed aerial vehicles, drones, etc.

Understanding the physiological inflict and psychological outcomes of directed energy is crucial to damage, incapacitate, disable and/or destroy military equipment, facilities, personnel and space assets. Advancements in the area can lead to unraveling safer applications, mitigation strategies and regulatory policies. However,paucity of data highlights the need for research in this field. Among the stressors that have the strongest influence on public health, noise is a key environmental component and infrasound emerges as an important area. Infrasound and other low-frequency sounds are present ubiquitously, ranging from natural phenomena to anthropogenic activities such as industrial facilities and low-speed machinery.[2] Emerging evidence highlights that infrasound exposure can influence human health, thereby affecting neurological, cardiovascular and psychological functions [Figure 1]. Occupational exposure to high-intensity acoustic and electromagnetic waves can result in symptoms such as dizziness, otalgia, hyperacusis and hearing loss.[3] The unique ability of infrasound to influence human health and physiological processes has been partially attributed to its low frequency and amplitude, which overlaps with the frequency range of some of the endogenous biochemical processes, such as those associated with cardiovascular, neuronal and vestibular responses. However, the vibration patterns within the human body are highly complex, often non-linear and influenced by various physiological and environmental factors, making direct comparison with externally propagated infrasound difficult in terms of both their physical properties and biological effects. Infrasound waves may travel far distances without losing much power, owing to their significant wavelength and minimal absorption.[4] Additionally, it spreads across most media, making it quite challenging to significantly reduce its impact.[5]

Figure 1.

Schematic overview of bioeffects of infrasound on human health. The illustration summarizes the interaction of low-frequency acoustic waves (<20 Hz), originating from both natural (volcanic eruptions, oceanic turbulence) and anthropogenic (aircraft, military detonations) sources, with human biological systems. Identified physiological targets include the vestibular, cardiopulmonary and neurological systems. These interactions may contribute to a spectrum of adverse outcomes such as sleep disturbances, cognitive dysfunction and anxiety-related symptoms. The figure further highlights the existing knowledge gaps and underscores the need for comprehensive mechanistic studies, longitudinal bio-surveillance and the development of evidence-based protective countermeasures, particularly within high-exposure occupational and defence-related settings. Figure created via www.BioRender.com

Systematic monitoring of these low-frequency sound waves has become increasingly important with increasing recognition of the physiological and psychological effects of infrasound, especially in occupational and military-related settings. A significant advancement in this domain was marked by the signing of the Comprehensive Nuclear-Test-Ban Treaty in 1996, which led to the establishment of the International Monitoring System (IMS), marking a milestone in advancing low-frequency sound monitoring technologies for the detection and verification of nuclear explosions.[6] The IMS consists of a 60-station network engineered to detect infrasonic signals from atmospheric nuclear explosions of at least 1 kiloton, with simultaneous confirmation from two or more stations within the network.[6] These stations use ultrasensitive micro-barometers and advanced noise-reduction systems to detect pressure fluctuations from sources such as volcanic eruptions, meteor entries, industrial blasts and nuclear explosions.[7] However, beyond this role, because of its long-range propagation and subtle biological interactions, infrasonic monitoring has found growing relevance in both environmental health studies and defence applications. The global distribution of IMS infrasound stations enhances our ability to triangulate source locations and monitor events across extensive geographic ranges. A visual representation of the worldwide distribution of these monitoring networks is provided in Figure 2. Understanding the function, design and deployment of these monitoring systems is essential for assessing the broader implications of infrasound exposure, which is relevant to both the public health and homeland security domains.

Figure 2.

(A) The chart illustrates the country wise distribution of operational International Monitoring System (IMS) infrasound stations. (B) Global distribution of infrasound monitoring stations that are part of the IMS under the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The image was created using https://www.ctbto.org/our-work/station-profiles as reference.

Despite being well-established internationally, the science of infrasound is still relatively new in India. Drawing attention to this issue is of utmost importance, as it is envisioned that such an effort would bring about public interest for scientific researchers and encourage them to establish a key link between environmental infrasound and their health effects.[8] From a military perspective as well, it is of utmost importance to ensure the well-being and safety of military personnel against infrasound exposures. This step will also lead to the development of potential mitigation strategies against the adversary use of infrasonic weapons. In-depth knowledge and understanding of infrasound and other DEWs can assist in minimizing the adverse outcomes pertaining to health for both military officers and civilians subjected to long-term exposure to such frequencies, thereby ensuring improved environmental and occupational safety standards in a densely populated and industrialized country.

The present review is comprehensive in nature and presents an interdisciplinary analysis of the physiological and psychological effects of the infrasound acoustics on humans. It systematically addresses both the beneficial and detrimental impacts of infrasound exposure, while emphasizing its emerging relevance in both biomedical innovations and occupational health contexts. Based upon current experimental and clinical findings, this review highlights the mechanistic pathways, unresolved scientific questions and underscores the need for standardized monitoring protocols. By bridging insights from health sciences, acoustic physics and biomedical research, the article aims to inform future research directions, foster technological innovations and evidence-based policy formulation within this rapidly evolving domain.

MOLECULAR AND MECHANISTIC INSIGHTS INTO HUMAN RESPONSE TO INFRASOUND ACOUSTICS

Exposure to acoustical environments rich in high-intensity infrasound causes psychomotor effects, such as annoyance, sleep disturbances, psychological distress and other physiological alterations pertaining to cognitive performance and cardiovascular and auditory systems in both animals and humans.[9] The underlying evidence supports the fact that noise acts as a common and frequently underrated threat to auditory and non-auditory health, thereby making it necessary to come up with possible solutions to eliminate the ill-effects it can cause to the general public at large. The following section of the present review article emphasizes on the possible effects of infrasound exposure on both animal and human models. The findings of some of the scientific studies pertaining to physiological alterations resulting from infrasound exposure are summarized in Table 1.

Table 1.

Overview of infrasound induced physiological alterations in animal model.^*

S.No	Frequency (Hz)	SPL (dB, weighting)	Duration	Studydesign	Subject	Target organ	Effect	Magnitude	Ref
1.	1, 10, 20	150, 160, 170 dB SPL	Continuous or intermittent	In vivo	Chinchillas	Ear	Tympanic membrane perforation, stapes subluxation, bleeding from the middle ear mucosa and tensor tympani, strial pathology, Reissner’s membrane rupture, endolymphatic hydrops, saccular wall rupture, hair cell damage and blood in the cochlear scalae.	↑	Lim et al.[10]
2.	8	135 dB SPL	1.5 hour	In vivo	Guinea pig	Ear	↔ for vestibular and ABR measures, ↓DPOAE amplitudes and ultrastructure damage observed in inner ear.	↔/↓	Feng et al.[11]
3.	16	120 dB	20 minutes	In vivo	Rat	Endocrine system	↑ Plasma ACTH and corticosterone, ↓ gastric mucosal blood flow	↑ / ↓	Nishimura[12]
4.	5	130 dB	24, 48, 72 hours	In vivo	Rat	Heart	Induced apoptosis in cardiac myocytes, ↑apoptotic gene expression	↑	Pei et al.[13]
5.	16	120 dB	1 hour x 4 days	In vivo	Rat	Brain	↓norepinephrine and dopamine concentration	↓	Spyraki et al.[14]
6.	2–20	120 ± 3 dB	24 hours	In vivo	Rat	Pancreas	No change in GLUT ratio and insulin concentration	↔	Pereira et al.[4]
7.	4–20	79-86 dB	1 hour	In vitro	Rat	Bone marrow mesench-ymal stem cells (BMSC)	↑ Proliferation, ↓ apoptosis, ↑ survivin expression	↑ / ↓	He and Fan[15]
8.	12–20	<90 dB	1 hour/day × 42 days	In vivo	Rat	Bone	↑ Fracture healing, ↑ BMC & BMD	↑	Long et al.[16]
9.	4, 12, 20	100 dB	0.5 hour x 5 days	In vitro	Mice	Osteoblast like MC3T3-E1 cells	↑ Osteoblast-like cell proliferation, differentiation, growth	↑	Bing et al.[17]
10.	2–20	120 dB	28 days	In vivo	Rat	Bone	No change in calcium and phosphorous level	↔	Zagalo et al.[18]
11.	8	130 dB	2 hours/day x 21 days	In vivo	Rat	Testes	↓ Methylation levels and methyltransferase activity	↓	Rui-Man et al.[19]
12.	8	130 dB	2 hours/day x 14 days	In vivo	Rat	Gastric system	↓ Gastric contractions, epithelial damage, ↑ gastric wall thickness, ↓ NOS expression	↓	Zhao et al.[20]
13.	2–20	120 dB	24 hours x 1, 6, 12 weeks	In vivo	Rat	Liver	No influence of such exposure on the liver lipid content of both sham and glucose intolerant groups.	↔	Martins Pereira et al.[21]

Note: ^*Reported sound levels are presented as given in the original studies. The standard unit for acoustic measurement is Decibels Sound Pressure Level (dB SPL). However, some reports use dB without specifying weighting. These values are reported here for transparency but should be interpreted cautiously, as direct comparison across unspecified and weighted (dB(A), dB(C), dB(Z)) values is not appropriate; Arrows in the Magnitude column indicate the direction of effect: ↑ = increase, ↓ = decrease, ↔ = no significant change. Abbreviations: ABR = auditory brainstem response, ACTH = adrenocorticotropic hormone, BMC = bone mineral content, BMD = bone mineral density, dB = decibel, DPOAE = distortion product oto-acoustic emissions, GLUT = glucose transporter, Hz = Hertz, NOS = nitric oxide synthase, SPL = sound pressure level.

Cardiovascular Response to Infrasound

The cardiovascular system, which serves as a central pump, is responsible for circulating blood, oxygen, nutrients and removal of waste products from the body tissues. Despite playing a crucial role in maintaining the overall health and well-being of living organisms, focus on studies investigating the ill-effects of low-frequency infrasound or acoustic vibrations below 20 Hz are limited.[22] Although inaudible to the human ear, infrasound can still affect the cardiovascular function in an indirect manner, leading to oxidative stress, vascular dysfunction and inflammation, thereby resulting in cardiac remodeling and fibrosis.[23,24,25] It is, therefore, of utmost importance to understand how infrasound alters the physiology of the cardiovascular system, especially in settings where exposure is either intermittent or continuous, e.g., areas contiguous to wind turbines, industrial zones and areas susceptible to natural disasters like storms and earthquakes. Short-term exposure to high-intensity infrasound may potentially influence cardiac contractility, highlighting cardiac tissue as a sensitive target of infrasound. Increased levels of infrasonic exposure result in alterations in cardiac ultrastructure and calcium metabolism [Figure 3] leading to mitochondrial swelling, oedema, platelet aggregation and capillary rupture.[26] These alterations are closely linked to disturbances in intracellular calcium homeostasis. Experimental evidence suggests, infrasound-induced calcium overload observed after a duration of 7 and 14 days of exposure may transiently augment the systolic function by elevating the contractile force. However, downregulation of Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 2 (SERCA2) activity impairs calcium re-uptake into sarcoplasmic reticulum (SR), ultimately impairing relaxation and resulting in diastolic dysfunction.[26] This aligns well with the observations where reduced SERCA2a expression, along with enhanced suppression by dephosphorylated phospholamban (PLN - an endogenous inhibitor), results in defective calcium cycling and impaired myocardial activity.[27] The pivotal role of SERCA2a in maintaining the contraction–relaxation cycle, highlights its potential as a therapeutic target in conditions of impaired cardiac function. At the cellular level, exposure to 8 Hz at 90 dB(Z) favours calcium accumulation within the cardiomyocytes, significantly damaging the ultrastructural components of the myocardium.[28] As a result, compromised membrane integrity facilitates excessive calcium influx via L-type channels, thereby impairing the efficiency of calcium transporters, vis-à-vis, Ca²⁺/Mg²⁺ ATPase and Ca²⁺/H⁺ ATPase. This imbalance drives cytosolic calcium overload, which disrupts oxidative phosphorylation, depletes ATP reserves, further impairing both synthesis and activity of SERCA2.[27] As the excitation–contraction mechanism of the heart relies on a precisely coordinated sequence of calcium influx, its release from ryanodine receptors and re-uptake into SR via SERCA2 can have deleterious consequences and any disturbance in this balance compromises the myocardial contractile cycle. While the initial upregulation of SERCA2 as observed by Pei et al.[26] may represent a transient compensatory response, its subsequent downregulation after prolonged infrasonic exposure of 7–14 days is indicative of impaired relaxation. Together these findings, underscore the crucial role of SERCA2 as a central determinant in mediating infrasonic cardiac injury, linking structural damage, calcium overload and energy depletion to progressive myocardial dysfunction.

Figure 3.

Mechanism of the infrasound-induced disruption of calcium metabolism in cardiac tissue. High-intensity infrasound exposure leads to ultrastructure cardiac damage, calcium channel dysregulation and impaired mitochondrial ATP production. The resulting calcium overload and reduced SERCA2 expression disrupts cardiac contraction–relaxation cycle, contributing to compromised cardiac performance. Figure created via www.BioRender.com

In addition to disrupting the calcium homeostasis, infrasonic exposure activates apoptotic pathways in cardiomyocytes. Exposure of 5 Hz at 130 dB(Z) upregulates pro-apoptotic proteins like Bax, Caspase-3, 8, 9 and first apoptosis signal receptor (FAS), while downregulating the expression levels of inhibitory apoptosis proteins (IAPs) such as Bcl-x, XIAP, cIAP-1 and cIAP-2. This loss of IAP-mediated caspase inhibition amplifies apoptotic signalling, while activation of the first apoptosis signal receptor/Fas ligand (Fas/FasL) pathway further complements this process by engaging death-inducing signalling complex, leading to Caspase-8 activation.[13] However, the extent of injury depends on the duration, target organ and intensity of exposure, clearly underscoring the target–dose–response relationship. It is still not unambiguously established that low-level exposure to infrasound always leads to adverse consequences at the organ, tissue, cellular and molecular level. The biological effect is highly dependent on the frequency and intensity of the sound, as well as the duration of exposure. Most research studies point out to the possible physiological and molecular disturbances, though few studies have documented the positive effects of infrasound. Reactivation of miR-29a, a potential target of the transforming growth factor-beta/suppressor of mothers against decapentaplegic 3 pathway, has been shown to inhibit angiotensin II − stimulated cardiac fibroblasts, which serve as the primary source of collagen in cardiac fibrosis.[29] These cells are known to play a pivotal role in the process of cardiac fibrosis, a major factor responsible for end stage heart failure in patients with hypertension and coronary heart disease, indicating that treatment with infrasound could have cardioprotective effects and might serve as a novel and efficient treatment strategy for fibrosis-related cardiac disorders.[13] In addition, studies on infrasound have shown that it can be used for combating cancer. The ultrastructure of tumour cells is directly impacted by infrasound, which also appears to make certain kinds of cancers more sensitive to chemotherapy, possibly as a result of membrane permeabilisation. When tumour cells are exposed to such low frequency sounds without the use of other therapeutic agents different effects are observed. These effects likely vary depending on the type of cells, the frequency and sound pressure level used and the exposure duration.[14,30] Notably, one limitation that exists till date is that much of the available evidence is derived from in vitro models, which lacks the complexity of systemic regulation observed in vivo. Future preclinical investigations should prioritize animal models with in vivo imaging of target organ dynamics, to gain deeper mechanistic insights. Complementing this, we believe that Organ-on-Chip platforms may further enable the study of cardiac functional dynamics under controlled experimental settings. On the translational front, conducting longitudinal epidemiological studies in occupationally or environmentally exposed individuals, together with real-time monitoring and biomarker profiling will be crucial for linking experimental findings to clinical relevance and informed therapeutic strategies. Additionally, endeavours are underway to explore the potential of infrasound as a non-invasive technique for cardiac monitoring in clinical settings by analysing infrasound produced by the heart.[31] These studies highlight the potential of infrasound to revolutionise the field of cardiology by providing a novel non-invasive method to detect cardiac abnormalities in early stages and prior to emergency situations. Together, these findings underscore the need for a nuanced approach to research, considering both the harmful and beneficial aspects of infrasound exposure to fully understand its potential applications and risks.

Vestibular and Balance Disturbances

Exposure to low-frequency infrasound and ultrasonic acoustic waves can trigger audio-vestibular symptoms. Isolated reports of vestibular symptoms such as dizziness and nausea, as well as auditory complaints, such as tinnitus, have been well documented in the literature due to exposure to infrasound emitted from rocket engines and wind turbines.[3] Low-frequency sound waves can stimulate the otolith organs and semi-circular canals of the inner ear, leading to altered vestibular responses. Animal studies suggest that exposure to infrasound may influence the endo-cochlear potential, leading to a shift in the electrochemical voltage, which drives the receptor current through the transduction channels of auditory hair cells.[32] The long-term implications of exposure to infrasound remain uncertain, although reports suggest that such exposure might alter sleep habits, disturb work performance, and undermine individual well-being.[33] Hensel et al.[34] investigated the effects of infrasound on the human cochlea by assessing the distortion product oto-acoustic emissions (DPOAEs) in individuals with normal hearing. Their findings demonstrated that infrasound exposure at 6 Hz and 130 dB(Z) SPL modulated DPOAE amplitudes, suggesting alterations in the inner ear function due to such exposure. Hiraide’s[35] research indicated that exposure to high-intensity infrasound, especially at 20 Hz and 163 dB(Z) SPL can lead to specific cochlear damage in animals, including outer hair cell degeneration and tectorial membrane alterations. The lack of notable morphological changes at lower intensities and frequencies, however, points to a threshold effect for auditory impairment caused by infrasound. Extrapolating these findings to occupational environments raises critical concerns, as even subtle vestibular disturbances can disrupt spatial orientation, balance, and operational performance in high-demand, acoustically challenging scenarios. It is well documented in the scientific literature that individuals residing near wind farms claim to experience patterns of sleep disturbances, headaches, dizziness and anxiety, collectively referred to as wind turbine syndrome.[36] Although infrasound generated by wind turbines and low-frequency noise have been linked to these symptoms, the scientific basis for this association remains a topic of debate. Comprehensive assessment, including controlled null trials carried out on infrasound, reveals that the sound levels generated by wind turbines are insufficient to cause direct harm.[37,38] Infact, 90% population residing in wind farms are unaware that they generate infrasound and also what exactly is infrasound. Moreover, studies have revealed that psychological factors, such as the nocebo effect, which occurs due to the negative perceptions of people about infrasound, are likely to influence the health concerns of those residing near wind farms.[38] The existing evidence on potential health effects of wind-turbine-generated infrasound is mainly derived from observational studies and self-reported symptoms. Although some individuals have reported experiencing cognitive and vestibular disturbances. These subjective complaints were not consistent with the objective assessments, including measurement of cortisol level, heart rate variability or actigraphy-based sleep quality data.[39,40,41] A major limitation in the current literature lies in the difference in both exposure assessment (modelled vs. measured infrasound level, distance from the turbines or laboratory simulations) and outcome evaluation (sleep quality, cognitive function and psychological well-being). Such methodological inconsistencies contribute to conflicting results and prevent meaningful quantitative synthesis of results across studies. The evidence base is fragmented and calls for well-designed investigations to clearly differentiate the potential physiological effects of infrasound from psychological factors, including the nocebo effect. In order to address public concern and misconceptions regarding wind turbine-generated infrasound, emphasis should be placed on evidence-based communication strategies. Additionally, future studies should pay attention to identify thresholds of exposure, underlying mechanistic pathways and protective strategies by conducting longitudinal studies with well-characterized populations to mitigate infrasonic-induced risk. Such research can lead to enhanced safety protocols, improved technology designs and potential therapeutic applications for vestibular and overall health.

Neuroharmonics of Infrasound

Emerging studies highlight the potential of infrasound to influence brain function and neurophysiology, altering cognitive performance, emotional states and sensory processing. The interactions with neurotransmitter systems, brainwave patterns or the vestibular pathways may be the underlying factors for these response. Understanding how infrasound affects the physiology of the brain is critical, especially in environments where low-frequency sounds are prevalent, such as industrial zones, wind farms and military operations. To gain insights into the physiological effects of infrasound and evaluate possible health hazards, and explore therapeutic applications for neurological disorders there is a need for extensive research in this field. Studies conducted on animals have demonstrated that infrasound may influence the brain, cardiovascular and respiratory systems. Brain being the most vulnerable exhibits[42] significant sensitivity to infrasonic waves, especially those below 10 Hz. The initial breakthrough functional magnetic resonance imaging (fMRI) investigation conducted in 2009 established a link between exposure to infrasound (at SPL between 90 and 110 dB(Z)) and low frequency sounds (12–500 Hz) with that of altered blood oxygen level-dependent response in the superior temporal gyrus and primary auditory cortex, and the major regions involved in high-order auditory processing.[43] Another pilot study conducted in 2017 demonstrated that infrasound up to 8 Hz triggers brain activity within the auditory cortex, provided SPLs are above the hearing threshold.[44] Ascone et al. [45] explored the effects of airborne infrasound [6 Hz, 80–90 dB(Z)] on human mental health, cognition, sleep quality and brain structure of over a 28-night period. No discernible variations in terms of mental health, cognitive performance or sleep quality were observed in the behavioural assessments conducted between the two groups (sham and test). However, a non-significant tendency towards physical weakness in the exposed group were reported by exploratory analysis. Additionally, neuroimaging analysis in the test group via voxel-based morphometry revealed reductions in regional grey matter volume in specific brain areas, including the bilateral cerebellum villa and the left angular gyrus (BA39).[45] The fMRI studies investigating the effects of near-threshold infrasound on brain connectivity revealed significant alterations in both local and large-scale neural connectivity during infrasonic exposure. In contrast to supra-threshold and no tone scenarios, regional homogeneity analysis suggested enhanced local connectivity following near threshold infrasound exposure in the right superior temporal gyrus (near the primary auditory cortex), anterior cingulate cortex and right amygdala.[46] These reported observations highlight the potential of infrasound to alter brain morphology and influence neural activity in regions associated with auditory processing, emotional regulation and autonomic control, although the documented alterations did not line up with measurable behavioural effects.

Infrasonic exposure of 16 Hz at 130 dB(Z) for 14 days resulted in notable cognitive impairments, including prolonged escape latencies and decreased time spent in the target quadrant during the Morris water maze test carried out in an animal model, unravelling deficits in spatial learning and memory.[47] Moreover, findings from molecular investigations revealed a significant downregulation of brain-derived neurotrophic factor (BDNF) and its associated tyrosine-kinase receptor B (TrkB) in the hippocampus of exposed rats, highlighting disruptions in critical neuroplasticity pathways.[47] Figure 4 presents an general overview of the possible mechanisms involved in infrasound-induced central nervous system (CNS) impairment.

Figure 4.

Highlights of infrasound induced CNS impairment due to calcium and Rho-associated coiled-coil containing protein kinase (ROCK) signalling. Exposure to high-intensity infrasound induces mechanical and biochemical disturbances in neurons, including calcium-influx mediated activation of calpain and Ras Homolog Family Member A (RhoA/ROCK) signalling. These cascades promote axonal cytoskeletal degradation, axonal beading, and progressive degeneration, ultimately leading to CNS impairment. Protective agents such as acetyl-leucyl-leucyl-norleucinal and Fasudil may attenuate these effects by stabilizing cytoskeletal integrity and preventing neuronal damage. Figure created via www.BioRender.com.

The biochemical and structural effects of acoustic vibrations on neurophysiology have been well documented in the literature. Liu et al.[48] examined the effects of infrasonic frequencies of 8 Hz at 90 and 130 dB(Z) on the intracellular calcium (Ca²⁺) ion concentration and hippocampal N-methyl D-aspartate 1 (NMDAR1 ionotropic receptor that are important in neurotransmission and synaptic plasticity). A distinct temporal expression pattern of NMDAR1 and alterations in the Ca²⁺ concentration at two different SPLs, with both being normalized by day 28 of the experiment, was reported. These findings highlight the reversible nature of NMDAR1 expression changes and Ca²⁺ ion fluctuations in response to infrasound, suggesting their potential implications for cognitive functions such as learning and memory.[48] Transmission electron microscopy (TEM) studies revealed significant ultrastructural damage in hippocampal neurons immediately after infrasound exposure (8 Hz, 140 dB(Z) for 2 hours daily), with signs of partial recovery after 1 week.[49] Additionally, elevated neuronal apoptosis after 24 and 48 hours of exposure was demonstrated by TUNEL labelling experiments. Furthermore, the peak expression of Heat Shock Protein 70 (HSP70), a crucial marker of the cellular stress response, at 24 hours post-exposure was confirmed by immunohistochemistry and western blot data.[49] The scientific contributions of Zhang et al.[50] highlight the pivotal role of astroglial connexin 43 hemichannels (Cx₄₃ HCs) in mediating cognitive functions such as learning and memory. These findings tend to reinforce the fact that activity of Cx₄₃ HCs in hippocampal astrocytes, results in excessive release of glutamate and ATP (Adenosine Triphosphate: a source of energy for use and storage at cellular level), and might be involved in learning and memory deficits induced by infrasonic exposure. Consistent with this finding, the “collusion hypothesis” proposes that microglia-derived glutamate not only elevates the extracellular glutamate concentrations but also suppresses astrocytic transporters. This hinders the reuptake of glutamate, and promotes excitotoxic stress, neuroinflammation and neural injury.[51] These changes are accompanied by elevated levels of proinflammatory cytokines, suggesting a strong interplay between neuroinflammation and cognitive dysfunction. Downregulation of Cx₄₃ HC expression significantly ameliorates deficits in learning and memory, thereby underscoring the potential of targeting astroglial mechanisms to mitigate environmental noise-induced neurocognitive disorders. These findings emphasize that while acute infrasound exposure can induce notable hippocampal damage and apoptosis, the potential for recovery exists. This underscores the need for further research to elucidate the mechanisms and long term effects of such exposures on neuronal health. Futuristic studies based on evaluation from in vivo models, advanced imaging of glial–neuron interactions, and targeted modulation of glutamate transport and Cx₄₃ HC activity could provide deeper insights into the causal mechanism and help identify potential therapeutic strategies.

The neuroprotective effect of the fibroblast growth factor 2/fibroblast growth factor receptor 1 signalling pathway against infrasound-induced astrocyte-mediated inflammation, thereby mitigating infrasound-induced CNS impairment, points to its potential for the development of novel treatments and therapeutic interventions.[52,53] A recent study sheds light on how inaudible infrasound alters functional connectivity (FC) in central resting-state brain networks, including the default mode (DMN), sensorimotor (SMN), and executive control network (ECN). According to reports, decreased FC in the DMN and increased FC in the SMN are indicative of disruptions in self-referential processing and sensorimotor integration, respectively. Whereas mixed alterations observed in the ECN represent convoluted effects on cognitive control.[54] These changes interestingly correlate with individual sensitivity, with FC alterations in the DMN and ECN associated with somatic symptoms and annoyance. Behler and Uppenkamp[55] investigated the neural processing of low frequency and infrasound stimuli, focusing on their perceived loudness and perceived unpleasantness. These researchers reported that both stimuli activate the primary and secondary auditory cortex, similar to higher frequency sounds, suggesting a continuity in auditory processing across frequencies. However, individual differences in the perception of loudness and unpleasantness are not linked to specific neural correlates. A pilot study exploring the potential impact of wind turbine infrasound (WTI) and low-frequency noise (LFN) on human mental performance and well-being revealed no discernible differences in cognitive performance or subjective well-being upon exposure, indicating that neither WTI nor LFN has a direct impact on mental performance or post-exposure health complaints.[56] These findings highlight the complexity of auditory processing and the variability in subjective experiences, emphasising the need for further research into the neural basis of low-frequency sound perception. Understanding these mechanisms can help mitigate potential health risks, guide the development of protective strategies, and inform regulations for noise control in environments where infrasound exposure is prevalent.

Beyond experimental investigations, the real-world scenarios have raised concerns about the possible biomedical/health implications of low-frequency and infrasonic exposure. Of particular relevance are the putative link between infrasound and Havana syndrome − a cluster of unexplained neurological symptoms reported in the literature where personnel might have been routinely exposed to atypical acoustic environments affecting the brain function, though it is still not scientifically well established and remains a mystery. The present review provides important context for understanding the translational significance of infrasound research for human health applications. The subsequent section addresses some of these issue as special topics, placing the biomedical evidence within applied and real-world perspectives.

SPECIAL TOPICS: TRANSLATIONAL PERSPECTIVES

Havana Syndrome: Biomedical Enigma and Controversies

Between the year 2016 and 2018, concussion-like symptoms, such as headache, tinnitus, cognitive manifestations, and other unusual sensory and auditory stimuli were reported by several U.S. diplomats residing in Havana. Similarly, abnormalities in the cognitive, oculomotor, and vestibular systems were reportedly experienced by Canadian diplomats and their families stationed in Havana, thus prompting widespread debate and several hypotheses regarding the etiology of these anomalous health incidents (AHIs), now termed as the Havana syndrome.[57] The primary cause behind such experiences remains unclear; however, some studies report exposure to microwaves,[58] cholinesterase inhibitors,[59] and acoustic attacks via devices capable of producing sounds at high levels[60] as a possible reason. A multidisciplinary diagnostic framework that focuses on exploring both the environmental (exposure to directed energy and toxins) and psychological dimensions to better comprehend Havana syndrome was put forward by Abouzari et al.[61] Researchers recommended a comprehensive and research-driven approach to unmask the underlying mechanism behind the clinical neuropsychological and vestibular manifestations to aid in accurate diagnostics. The crucial regulatory pathways of neuropsychological disruption in the Havana syndrome are highlighted in Figure 5. The mystery, as it persists, cannot be unequivocally established that the bioeffects were really manifested in plausibly exposed individuals.

Figure 5.

Putative neuropsychological disruptions associated with directed energy exposures. Figure created using from reference.[62] Figure created using Microsoft PowerPoint. Abbreviations: BDNF, brain-derived neurotrophic factor; GDNF, glial cell line-derived neurotrophic factor, IGF-1, insulin-like growth factor 1; IL-1, interleukin 1, IL-10, interleukin 10; NGF, nerve growth factor; ROS, reactive oxygen species.

Insights gained from the report of F.B.I.’s Behavioural Analysis Unit reveal the possibility of Havana syndrome being considered as a functional neurological disorder, termed as mass psychogenic illness, wherein a feedback loop develops between sensations, perception and anxiety, leading to the development of negative and potentially harmful symptoms, irrespective of whether the person is exposed to an attack. Consistent with this view, findings from the National Institute of Health study revealed no conclusive evidence of traumatic brain injury or any biological abnormality in the MRI scans obtained from patients experiencing neurological symptoms, pertaining to Havana syndrome, supporting the role of psychological factors, rather than structural brain damage behind these manifestations.[63] On the other hand, an exploratory study led by Chan et al.[64] revealed no significant differences among individuals reporting AHIs and control participants with respect to any clinical biomarker measurement and analysis, further complicating the interpretation.

The inconsistency across scientific studies reflects the unresolved nature of Havana syndrome and the challenges in establishing a definitive causal mechanism. While the psychogenic factors have gain wide attention, a physiological basis, possibly linked to acoustics or directed energy exposure, cannot be ruled out. This uncertainty is pertinent to infrasound research, as its neurophysiological and psychological effects, vis-à-vis excitotoxic stress and neuroinflammation offer a mechanistic explanation for symptoms like headaches, tinnitus, fatigue and cognitive impairment. Although the direct association of Havana syndrome with infrasound, microwaves and radiofrequency (RF) exposure remains hypothetical, the overlap in clinical manifestations underscores why this condition is pertinent even in today’s scenario and hence forms a part of this review.

Future research should aim to develop reliable diagnostic frameworks capable of distinguishing psychogenic origins from genuine exposure-related mechanisms. In our view, this may call for integration of advanced neuroimaging, electrophysiological testing and biomarker profiling with standardised monitoring. Simultaneously, experimental models such as neuronal cultures, animal models and Organ-on-Chip platforms are crucial to systematically investigate the implications of potential exposure to infrasound, microwaves and radiofrequency under controlled conditions. While experimental in vivo and in vitro models do provide controlled insights into the potential mechanisms, their extrapolation to humans is limited to a great extent by the physiological and other environmental differences. Consequently, longitudinal epidemiological studies in higher-risk populations, coupled with predictive modelling studies, using AI/ML approaches are needed to elucidate the possible disease trajectories and long-term health outcomes.

Infrasound in Strategic and Civil Context

Low-frequency and infrasound acoustics, which alter the neural system, cognition and well-being, present both challenges and opportunities for innovative applications. By exploring the biological effects and applications of infrasound, it is possible to develop advanced sensors, sound-based detection systems and even non-lethal weaponry. Strategic benefits could be gained by military innovations influenced by natural phenomena, such as infrasound-sensitive sensors modelled after the ability of elephants to detect distant threats. In addition, the potential use of infrasound as a non-lethal weapon to disrupt adversary communications or induce disorientation, nausea and pain[65] has gained significant attention. The unrealized potential of infrasound in defence and reconnaissance tactics is further highlighted by futuristic technologies, such as the U.S. Air Force’s portable navigation device, which utilizes ultra-low acoustic frequencies to provide information on direction-finding and alternative positioning schemes for military teams operating without GPS access.[66] On the other hand, active sonar sensors can be employed by military units specializing in naval anti-submarine warfare for effective submarine monitoring and underwater object detection, thereby facilitating timely detection of submarine launched ballistic and cruise missiles.

Low-frequency sound or infrasound with the potential to detect seismic events, such as earthquakes and volcanic eruptions,[67] holds great promise for improving the disaster management systems. With the advent of infrasound-based early warning systems, especially in areas prone to natural disasters, critical alerts before the occurrence of catastrophic events can help save maximum lives. Additionally, addressing the concern of infrasonic waves generated from large-scale industrial projects such as wind turbines and industrial machinery on the environmental front can improve public health and well-being. Furthermore, as countries across the globe aim to strengthen their space and aerospace technology, research and development pertaining to this field can help build new acoustic systems, navigation devices and countermeasures that complement both civil and military domains alike.

TRANSLATIONAL POTENTIAL OF INFRASOUND: FROM THERAPEUTICS TO TECHNOLOGY

While often associated with natural disasters, infrasound acoustics holds immense potential for beneficial applications across fields such as health sciences and smart technology development. The science of infrasound holds promising potential for revolutionary applications in the health sector and disease management. The electric, thermal, chemical and acoustic energies generated within humans due to respiration, heart rate, blood pressure and muscular contraction can be detected via wearable technology such as implantable sensors, wireless devices and lab-on-chip nano sensor platforms. Biometric monitoring plays a crucial role in assessing health and managing diseases by tracking vital physiological parameters in real time. Introducing infrasound and other low-frequency sound waves can complement biometric monitoring by offering non-invasive strategies to monitor and manage various health conditions, particularly those requiring long-term supervision and therapeutic intervention. Gilliam et al.[68] in this domain made a significant contribution by introducing a novel method called In-ear infrasonic haemodynography (IH) to monitor cardiovascular health. The proposed technique utilised in-ear headphones equipped with sensors to detect low-frequency (<20 Hz) vibrations produced by vital organs. With a correlation coefficient of 0.99, their study revealed a strong relationship between IH measurements and electrocardiography (ECG) data. Additionally, the IH accurately differentiated between sinus rhythm and atrial fibrillation and effectively monitored variations in heart rate during breathing exercises, mirroring the efficacy of the conventional ECG technique. These findings suggest that IH technology offers a continuous, non-invasive and wearable solution for real-time cardiovascular monitoring. Similarly, Meniere’s disease, an inner ear condition marked by endolymphatic hydrops that often leads to vertigo and hearing loss in humans, has been treated with a therapeutic device called the Meniett, that utilizes infrasound in the range of 6–9 Hz.[69] On the other hand, investigations on in-ear infrasonic earbuds are being carried out for their ability to monitor and influence neural activity, thereby aiding in the management of conditions such as anxiety, depression and chronic pain.[64] The underlying technology relies on infrasound to promote relaxation and stimulate neuroplasticity, providing a non-invasive, portable alternative for therapeutic intervention. Apart from this, the scientific literature documents the positive influence of infrasound waves in wound healing process, mediated via enhanced fibroblast migration, collagen synthesis, angiogenesis and modulation of mechano-transduction pathways. These acoustic stimulation, in particular, have shown great promise in enhancing bone growth, osteogenic differentiation of bone marrow stem cells, bone mineral density, thereby accelerating fracture healing and promoting tissue regeneration in chronic wounds.[70] Evidence from animal models and in vitro experiments support these observations. Long et al.[16] demonstrated that exposure to low sound pressure level (<90 dB(Z)) infrasound at 12–20 Hz for 30 minutes twice a day, enhanced fracture healing in rats, with treated animals showing higher bone mineral content and density compared to the control. Complementing this in vivo observation, He and Fan[15] reported that in vitro exposure of rat BMSCs to infrasound at 16 Hz, 90 dB(Z) for 60 minutes markedly enhanced proliferation and osteogenic differentiation, reduced apoptosis by upregulating the expression of surviving an anti-apoptotic protein, indicating a mechanistic role in cell survival.

Building on these findings, we believe that the therapeutic applications of infrasound are promising, non-invasive alternative and can complement the current wound healing methods under investigation, such as laser-based therapies. Besides the added advantage of cost-effectiveness, it is beneficial for public health settings and military field operations, where the advanced medical infrastructure may be limited. An important limitation to consider is that human studies on low acoustic stimulation are scant. Consequently extrapolating findings from animal or in vitro models may not fully reflect the physiological responses in humans, posing a significant challenge for clinical translation. Thorough investigations must be conducted to fully comprehend the mechanisms underlying their interaction with the biological systems. In particular, future research should employ the 3D tissue constructs and Organ-on-Chip platforms as physiologically relevant models to elucidate multicellular interactions, mechanotransduction and extra-cellular matrix remodelling under precisely controlled acoustic stimulation. Systematic investigation of frequency, intensity and duration-dependent effects will be crucial to establish optimal therapeutic parameters.[70] Future investigations might unravel new prophylo-therapeutic approaches, thereby enhancing the utility and ensuring the safety and efficacy of infrasound in medical practice. While preliminary findings point to the promising potential of infrasound in the field of diagnostics and therapeutics, the current evidence base remains limited and largely speculative. Much of the data is derived from in vitro models and animal experimentation, making translation to human health uncertain. Additionally, variability in exposure parameters such as frequency, sound pressure level, duration, and inconsistencies in outcome reporting, limit the reproducibility and make cross-study comparison challenging. To address these gaps, future research must prioritize standardized protocols, larger cohorts and rigorously controlled human trials to establish both the safety and efficacy of infrasound in these domains.

Technological advancements in the field of acoustics have opened new avenues for advanced computational integration, thereby enabling precision sensing, real-time monitoring, analysis and applications across diverse domains. In this regard, the integration of artificial intelligence and machine learning models (AI/ML) might enhance the potential of a therapeutic device to provide real-time diagnostics by analysing infrasound signals. This would offer a new dimension in early disease detection, particularly in cardiovascular and respiratory conditions. One such breakthrough in this area is the novel development of the world’s first AI-ready infrasound stethoscope (FDA approved-2022) developed by the Israeli start-up company Sanolla, which uses low-frequency sound waves to detect subtle physiological changes in the body that conventional methods often overlook. The integration of machine learning algorithms with modern medical techniques, such as digital stethoscopes capable of capturing both audible and inaudible lung sounds, facilitates accurate diagnosis of Covid-19 and related respiratory conditions. These systems demonstrate an approximate sensitivity and specificity of 97% and 93% respectively, underscoring the potential of AI-enhanced infrasound analysis as a non-invasive, cost-effective and precise diagnostic modality within the field of pulmonary medicine.[71] Leveraging the effectiveness of ML in enhancing medical diagnosis, a similar approach has now been extended to explosion monitoring. In scenarios where real-world data are limited, synthetic infrasound datasets have been employed to train ML models to reliably detect large explosions with over 90% accuracy, with successful validation against actual explosion recordings.[72] Apart from this, studies focusing on an AI-driven approach to distinguish between earthquakes and man-made explosions using seismic and infrasound data is gaining attention to enable real-time detection and classification of seismic anomalies with improved accuracy. Together, these innovations point to a future where infrasound and AI become a fundamental pillar of modern personalized medicine, facilitating improved diagnostics and treatment efficacy, and monitoring of seismic anomalies, thereby providing new insights into the intricacies of human health and global surveillance systems. In essence, novel advances in infrasound research could position India as a leader in cutting-edge technologies, while enhancing national security, disaster preparedness and environmental sustainability.

CONCLUSION AND FUTURE OUTLOOK

The underlying potential of infrasound and other low-frequency acoustic waves to alter human physiology and psychology highlights the importance of continued investigations in this area. Exposure to such frequencies, though often subtle, can result in various health complications, as alluded to above. Understanding the possible mechanisms underscoring these risks is crucial for developing advanced strategies to mitigate adverse outcomes, especially in environments with high infrasound levels, such as industrial sites, wind farms or areas prone to calamities such as earthquakes and volcanic eruptions. The integration of biotechnology and molecular biology presents exciting possibilities for advancing infrasound research. By leveraging cutting-edge technologies, such as genetic analysis and molecular profiling, researchers and scientists could gain in-depth knowledge and a better understanding of the biological mechanisms through which infrasound affects the human physiology. Such an interdisciplinary approach in the near future may aid in the development of more accurate and reliable diagnostic tools and techniques, as well as novel therapeutic interventions to balance out the ill-effects of infrasonic exposure. Ultimately, the combination of advanced technologies with biological insights offers Immense scope of improvement of public health response, promote preventive measures and enhance the overall well-being of individuals residing in the areas that are increasingly impacted by low-frequency sound.

Advancing infrasound research is crucial from a public health perspective and as a strategic priority for the defence sector. Military operations expose troops to intense low frequency acoustics, such as those generated by artillery shelling, heavy-lift aircrafts, missile launches and standoff detonations, that can result in physiological and psychological distress. The existing body of knowledge pertaining to the underlying biophysical mechanism of infrasound-induced alterations, both short and long-term remains inadequate to carry out informed comprehensive health risk assessments and develop effective mitigation strategies. To advance this science, attention should be drawn towards carrying out targeted mechanistic studies that dissect the cellular, molecular and systemic responses to infrasound. Simultaneously, establishment of continuous, theatre-wide surveillance systems is equally important to facilitate early detection of physiological perturbations. Such a proactive monitoring would enable timely interventions to prevent the progression of sub-clinical effects, which may otherwise degrade performance or compromise operational readiness. Finally, the development of evidenced-based countermeasures, ranging from smart-ear defence to real-time analytics is essential for safeguarding the cognitive abilities of individuals, critical to mission success. Therefore, integration of these scientific and operational threads is imperative to address the existing limitations, and to strengthen the physiological resilience of defence personnel operating in an acoustically complex and challenging battle space.

Given the current knowledge gaps, future investigations on infrasound must focus on addressing several shortcomings. Establishing precise exposure threshold by determining the intensity and duration of infrasound exposure, capable of eliciting a measurable physiological or psychological response in humans remains an immediate research need. Equally important is the development of standardized metrics, including harmonized SPL and frequency weighing protocols, to ensure comparability and reproducibility across studies. Additionally, identification of robust diagnostic markers − molecular, genetic or physiological is critical for enabling early detection and monitoring of both short-term and long-term effects of infrasound. In parallel, longitudinal cohort studies are essential to clarify how sustained exposure to infrasound impacts cardiovascular, neurological and cognitive health trajectories over time. Collectively, addressing these directions will not only advance the scientific understanding of infrasound bioeffects but will also inform public health policies and measures to ensure safer environmental and occupational exposure standards.

Availability of Data and Materials

The datasets used and/or analysed in this article are available from the corresponding author. This article contains only unclassified and non-confidential data.

Author Contributions

PK outlined the review work, conducted the literature search, analyzed the relevant studies, and drafted and wrote the initial and final version of the manuscript. RBY did the figures for the manuscript. NA and SG contributed to the literature search, manuscript structuring, and provided feedback during the revision process. RA conceptualized, provided critical guidance, overall supervision, strategic direction, expert insights, drafted and finalized manuscript, and coordinated the review and submission process. All the authors revised and approved the final version of the manuscript and agreed to be accountable for all aspects of the work, accuracy, integrity, and appropriate investigation of the manuscript. The authors are qualified and designated as authors qualification for the authorship.

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Conflicts of Interest

The authors declare no conflicts of interest.