Effects of Infra- and Ultrasound on the Brain
Condition: Brain Function; Ultrasound; Cognitive Function; Well-being; Depression; Sleep
MeSH terms: Depression
Study type: Interventional

Summary: 
      Findings in neuroscientific research show that the environment one lives in has measurable
      effects on brain morphology and functioning. Human exposure to airborne infra- and ultrasound
      has been constantly increasing during the last decades. For instance, the European Renewable
      Energy Directive, established in 2009, lead to an increased use of wind turbines, generating
      infrasound. The EU Directive states that until 2020 a 20% of the EUs' total energy needs is
      to be generated with renewables, therefore the current infrasound load in the European
      environment will increase further. Similarly, ultrasound is ubiquitous in the modern public
      environment, emitted from public address systems, animal repellents, industrial machines,
      even toothbrushes. The present study aims to investigate potential long-term effects of
      exposure to infra- and ultrasound on subjective well-being, cognitive and brain functioning,
      as well as on brain structure. The study will apply a randomized-(placebo) controlled
      single-blind approach to investigate this subject.
    

Detailed description: 
      Regarding effects of infra- and ultrasound on the brain, a pioneer study demonstrated that
      exposure to non-audible infrasound was associated with changes of neural activity across
      several brain regions, including areas involved in auditory and emotional processing, as well
      as autonomic control. These findings indicate that subliminal infrasound may have pathogenic
      effects. Research also indicates that low intensity focused ultrasound (LIFU) modulates the
      BOLD signal. However, the impact of ultrasound on auditory and other brain regions remains
      broadly unclear until today. Regarding adverse effects of low frequency noise on (mental)
      health and cognitive functions, preliminary evidence (summarized by two reviews) suggests
      mainly negative effects on sleep, stress levels (both subjective and objective; i.e. cortisol
      levels), headaches, fatigue, concentration, and memory. These reviews do however not
      explicitly address audible low frequency noise vs. non-audible infrasound.

      Research on the effects of infra- and ultrasound on cognitive functioning and well-being is
      in the fledgling stage. The few studies published so far vary strongly in their applied
      methods and results. Repeatedly, the media has covered stories about individuals suffering
      from 'ultrasound-sickness', a condition where the affected person suffers from headache,
      nausea and pain. In line with these subjective accounts, a review paper suggested that
      ultrasound exposure can be associated with hyperthermia, nausea, headaches, tinnitus and low
      blood pressure, as well as with neural excitability, irritation, memory problems and
      difficulties with concentration and learning, suggesting adverse effects of ultrasound
      exposure regarding (mental) health and cognition.

      Nonetheless, there are also indicators of positive effects of these types of sound; a study
      suggested that brief bursts of infrasound may have a positive effect on cognitive function.
      Also, pioneer works in the field are currently testing ultrasound therapy for Alzheimer's
      patients. It appears, that the effects (positive vs. negative) may be highly variable;
      depending upon the frequency, sound pressure levels and duration of exposure; as well as the
      quality of sound (mixed audible and non-audible vs. purely non-audible). Future studies need
      to clearly define these variables in order to be able to make clear statements about effects.

      The present study will hopefully shed further light on the long-term effects of (non-audible)
      infra- and ultrasound regarding human brain connectivity, structure and function, related
      cognitive functions and overall well-being. This may also lead to a more sophisticated and
      fact-based debate about 'noise pollution' of modern human living-environments.

      Healthy participants, who gave their written consent, will be exposed to infra- or ultrasound
      for 28 consecutive days during their night sleep. The sound sources produce sound that is at
      least 10 dB below the hearing threshold. The sources were designed to mimic exposure to
      infra- and ultrasound in everyday life. The construction and calibration of the sources was
      realized by experts of the Physical Technical Federal Institute of Germany (Physikalisch
      Technische Bundesanstalt; PTB), located in Braunschweig. Sound sources will be installed and
      gauged at the participants' bedrooms, following a standardized procedure and emit sound for 8
      hours during the participants' typical sleeping time. N = 60 participants will be randomized
      to one out of four conditions:

        1. Infrasound verum (n = 20; frequency = 6Hz, sound pressure = 85dB)

        2. Infrasound placebo (n = 10)

        3. Ultrasound verum (n = 20; frequency = 22.4 kHz, sound pressure = variable +/- 10 dB)

        4. Ultrasound placebo (n = 10); (single blind procedure).

      First, participants, age 18-40, will be screened for eligibility. In addition, a hearing
      assessment will be conducted to assure normal auditory ability of all participants. Before
      and after the sound exposure period, participants will be tested using psychological and
      (neuro-)cognitive test batteries and questionnaires in order to assess psychiatric and
      somatic symptoms, well-being and cognitive functioning (particularly tasks that also
      represent everyday cognitive challenges and assess executive functions); (T1, T2).
      Furthermore, sensitivity to sound (including to infra- and ultrasound) and current exposure
      to different sound sources (T1 and T2) will be assessed with questionnaires. In addition,
      Magnet Resonance Imaging (MRI) will be conducted in order to illuminate morphological and
      functional brain changes (T1 and T2). In the scanner, participants will execute a spatial
      n-back task. The task assesses participants' working memory and is also suited to assess
      stressful reactions due to permanent cognitive load - thus constituting a 'proxy' for a
      stressful working task in real life. During the n-back task, a dot is presented sequentially
      at different positions in a grid. Participants are instructed to indicate whether the
      currently presented dot coincides with the dot presented 3 trials before for each of the
      presented dots. During the 4-week exposure period through infra-/ ultrasound, participants
      will also fill out weekly questionnaires, assessing well-being, general health levels,
      psychiatric and somatic symptoms, quality of sleep, headache and overall quality of life.
    

Intervention name(s): Infrasound (85 dB; 6Hz) source; Ultrasound (10dB below hearing threshold; 22.4 kHz) source; Infrasound dummy source; Ultrasound dummy source
Intervention type(s): Device; Device; Device; Device
Intervention description(s): the infrasound source will emit inaudible 6Hz sound for 8 consecutive hours during participant's night sleep, local sound pressure (at participants head) will be calibrated at 85 dB; the ultrasound source will emit inaudible 22.4 kHz sound for 8 consecutive hours during night sleep; the infrasound dummy source looks exactly like the according verum infrasound source but produces absolutely no sound; the ultrasound dummy source looks exactly like the according verum ultrasound source but produces absolutely no sound
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science