Perspective: Hippocampal theta rhythm as a potential vestibuloacoustic biomarker of anxiety

Abstract

Anxiety disorders are the most common mental illnesses — afflicting 19% of Americans every year and 31% within their lifetimes — yet diagnoses remain based on symptom checklists because existing technologies have yet to produce biomarkers sufficiently robust for clinical use. Some techniques provide superior spatial resolution of deep brain regions implicated in anxiety but have poor time resolution; while others measure signals in real time but lack spatial resolution. Often, the goal of probing deep brain regions in humans for anxiety research is to measure a putative analogue of a mammalian brain rhythm linked to behaviour that is suggestive of anxiety. This 4–12 Hz, 1–2 mV, behaviourally modulated, nearly sinusoidal “hippocampal theta rhythm” (hTheta) is one of the largest normal extracellular synchronous signals in mammals and although it has been linked to anxiety processes, its function remains unclear. This paper reviews the literature on hTheta as it relates to anxiety and sensory, in particular vestibuloacoustic, signals, concludes that hTheta can modulate sensory signals during anxiety and posits that such modulation of vestibular signals may be an anxiety biomarker that could be detected non-invasively in humans.