A team of researchers has reported new evidence about the cause of auditory hallucinations, suggesting that in schizophrenia, and perhaps other illnesses, it may be traceable to an abnormality in the functional organization of part of the brain’s auditory cortex.

If confirmed in subsequent research, this would suggest that vulnerability to hallucinations may be detectable very early in life, long before psychiatric symptoms become apparent.

The research team was led by Sophia Frangou, M.D., Ph.D., of the Icahn School of Medicine at Mount Sinai. On November 1st, she will receive a BBRF 2019 Colvin Prize for Outstanding Achievement in Mood Disorders Research; she is also a 2008 BBRF Independent Investigator and 2002 Young Investigator.

The team used functional MRI imaging driven by a high-powered magnet to compare the auditory cortex of 16 patients with schizophrenia with those of 22 unaffected controls. The high-resolution scans were obtained while each individual passively listened to a series of sounds ranging widely across audible frequencies, first from low to high (88-8000 Hz) and then in reverse order.

Each of the patients in the study had a history of frequent (in many cases, daily) auditory hallucinations, which, at the time of the testing, were in remission thanks to antipsychotic medications. Knowing they were in remission enabled the team to compare their auditory cortex responses in a non-hallucinatory state to those of people who never experience hallucinations. About 80% of people with schizophrenia experience auditory hallucinations, which are not only distressing to patients but increase the risk of suicidal and aggressive behavior, the team notes.

Experts have debated for years about whether hallucinations are caused by “bottom-up” or “top-down” factors in the brain—i.e., factors affecting the perceptual apparatus itself or problems in high-order interpretation of sensory signals in the brain. Results obtained by Dr. Frangou and colleagues suggest the earliest deficit involves bottom-up processes.

Specifically, their scans revealed that schizophrenia patients with a history of regular hallucinations had abnormalities in primary sensory processing—in what scientists call the tonotopic organization of the auditory cortex. Tonotopy refers to the ordered representation of sound frequencies. Tonotopic maps of patients, as compared with controls, revealed that patients had greater activation in response to most sound frequencies. The team also noted a kind of “scrambling” in the way patients' auditory cortices mapped the range of sounds presented during the fMRI scanning.

Importantly, the tonotopic organization of the auditory cortex is established during prenatal and early postnatal life; it follows a genetic blueprint, the researchers explained. Thus, if the team’s findings are replicated, they will indicate that deviance in the organization of the auditory system actually begins prior to the development of both hearing and speech—and on average, 15-20 years before the onset of psychotic symptoms in people with first-episode episode psychosis, which often marks the onset of schizophrenia.

This means that the tonotopic organization or other abnormalities in the organization of the auditory cortex are potential early-life biomarkers for vulnerability to hallucinations as well as schizophrenia, the team said.

The team’s results, which appeared in NPJ Schizophrenia, are informative about the symptom of auditory hallucinations particularly within the context of schizophrenia. It is unclear if similar problems are present in other disorders, including bipolar disorder and depression, in which hallucinations sometimes develop. The team next hopes to replicate and expand these results and to quantify tonotopic disruption in the auditory cortex during hallucinatory experiences.

The research team also included Iris Sommer, M.D., Ph.D., a 2007 BBRF Independent Investigator and 2005 Young Investigator; and Priti Balchandani, Ph.D., a 2015 BBRF Young Investigator.