“Hearing voices no one else can hear isn’t a good sign, even in the wizarding world.” – J.K. Rowling, Harry Potter and the Chamber of Secrets
Do people actually hear voices, or are the sounds just figments of their imagination? Those who truly hear disembodied voices are likely experiencing a particular type of hallucination. Historically, hallucinations have been a powerful tool in storytelling, popping up in everything from the Euripides’ Greek tragedies to Shakespeare’s plays and more modern-day stories of demonic possession [1, 2]. Sometimes these voices appear to have good intentions, like those which inspired Joan of Arc, while others seem to taunt or even torture, like those which ‘possess’ their victims, forcing them to do unthinkable things . Hallucinations have captivated us for centuries, but the neurobiological basis for these phenomena is not well understood.
A hallucination can be defined as a sensory experience (seeing, hearing, smelling, tasting, or feeling something) that occurs in the absence of an external stimulus (object or person is not actually there). Hallucinations that involve hearing voices are called auditory verbal hallucinations and are symptoms of a variety of neurological disorders (e.g. epilepsy, mood and behavior disorders, schizophrenia), but also occur in healthy individuals. They can vary in tone, be male or female, young or old, have different accents, be in the third person, or even be more than one person. Sometimes they are non-verbal, and sound like a bunch of mumbling . In many cases, the voices sound threatening, like they want to harm the individual and might be an underlying reason for why people who have hallucinations have the sensation of being possessed. Intriguingly, the concept of possession is still prevalent in the belief systems of some non-Western cultures. [5, 6]
To understand how hallucinations form, researchers use different approaches. Many involve neuroimaging of the brain using techniques like computerized tomography (CT) or magnetic resonance imaging (MRI), which allow identification of lesions that may be associated with hallucinations. Researchers also look for parts of the brain that may be altered in size . Functional magnetic resonance imaging (fMRI) or functional neuroimaging allows scientists to directly observe what parts of the brain are active during a hallucination. fMRI allows a researcher to observe a person’s brain activity in real time: as a person is shown an image that makes them happy or sad, the fMRI can record what parts of the brain respond emotionally. The same can be done when someone experiences an auditory verbal hallucination.
Several research groups have conducted analyses on large collections of fMRI studies and revealed which parts of the brain seem to be most active during auditory verbal hallucinations . These include areas important for speech and memory. Speech centers are located on the outermost part called the neocortex. Not only is the neocortex responsible for processing information related to speech, it handles a host of other ‘higher-order’ functions like vision and hearing. Dysfunction in these areas has been attributed to all types of hallucinations including auditory verbal hallucinations. The hippocampus forms memories by integrating new information received from centers in the neocortex with recycled information that comes from old memories . Impaired memory formation is a symptom of neurological disorders like schizophrenia and appears in patients who also experience auditory verbal hallucinations.
There has been a growing body of evidence to support the role of the hippocampus in auditory verbal hallucinations. Neuroimaging of a patient’s brain while experiencing auditory verbal hallucinations shows a correlation with increased hippocampal activity . There are a number of reasons why this might be happening. Information from the neocortex is delivered to the hippocampus via different neural circuits. If connections along this circuit are disrupted, this can lead to elevated activity in the hippocampus and auditory verbal hallucinations. There is also evidence to suggest that abnormal communications between neurons within the hippocampus can lead to auditory verbal hallucinations . How might the latter work? The hippocampus contains a specialized set of neurons, called basket cells, which express a compound called GABA. GABA is a chemical messenger that gets sent from basket cells to the workhorses of the hippocampus, pyramidal cells, to inhibit them from being active. Basket cells know how much GABA to release because they are instructed to do so by another compound called glutamate. Basket cells sense levels of glutamate in their environment via a receptor molecule called NMDA. In some cases of schizophrenia NMDA isn’t working properly and basket cells can’t sense the glutamate surrounding them. When basket cells can’t respond to glutamate, pyramidal cells remain active and ultimately result in auditory verbal hallucinations. Now, this is just one possible way researchers believe we can hallucinate hearing voices. There are a number of other proposed theories involving other parts of the brain including the thalamus (important for relaying motor and sensory signals to the right parts of the cerebral cortex for processing) [12, 13]. As techniques evolve to more readily study the connectivity of the brain and to study brains of patients while they are actively experiencing hallucinations, we’ll be able to piece together how some people quite literally hear voices in our heads.
One possible way improper communication between neurons within the hippocampus can lead to auditory verbal hallucinations. If basket cells are unable to respond to glutamate because their NMDA receptors aren’t functioning, they can’t produce enough GABA to negatively regulate pyramidal cells. Over-activation of pyramidal cells may result in auditory verbal hallucinations.
Researchers can also use fMRI to create therapies to non-invasively treat patients who experience auditory verbal hallucinations . This kind of therapy targets neurofeedback signals (e.g. visual stimuli) to specific regions of the brain that may be the source of auditory verbal hallucinations. The goal is to help restore normal activity to these brain regions and eliminate the hallucinations. A diagnostic tool with therapeutic potential? Better start telling those voices to pack their bags.
Jennifer Lovick (@drjkyl)
Senior Editor, Science in Entertainment, Signal to Noise Magazine
PhD, Molecular, Cell, and Developmental Biology
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