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Finding the Neurobiological Mechanism for Hallucinations and Delusions

By: Sai Srihaas Potu

The personal, cultural, and clinical significances of hallucinations have changed in the 200 years since they were defined by Esquirol as “the intimate conviction of actually perceiving a sensation for which there is no external object.” There is a growing recognition that hallucinatory experiences attend a wide variety of psychiatric diagnoses and can be part of everyday experiences for people who do not meet the criteria for mental illnesses.


For the experiencer, hallucinations can have important personal meanings, and for clinicians, they are also significant in a variety of ways, including as diagnostic symptom and as factors which may impact on functioning and prognosis, and therefore potentially the necessity of treatment.


Similarly, delusional thoughts are common among patients with mental illnesses. These non-cognitive symptoms have important clinical implications as they contribute prominently to behavioral disturbances, institutionalization, and caregiver burden. However, the etiologic factors underlying delusions remain unclear.


Conceptually, delusional thoughts may be associated with memory deficits and poor insight. For example, the inability to recall accurate information may foster inaccurate beliefs. Poor insight, defined as reduced awareness of cognitive or functional deficits and impaired intuitive understanding, may undermine the patient’s appreciation of the illogical nature of these beliefs. While impaired memory and insight may be linked to delusional thoughts, the relationships are not necessarily causal and the extent of relationships and the neuropathological processes that mediate them are not known.


A new study from researchers at Columbia University Vagelos College of Physicians and Surgeons has found evidence of a potential neurobiological mechanism for hallucinations and delusions that fits within the hierarchical model of psychosis and can explain their clinical presentation.


Columbia researchers Kenneth Wengler, Ph.D., a Postdoctoral Research Fellow, and Guillermo Horga, MD, Ph.D., Florence Irving Associate Professor of Psychiatry, investigated the neurobiological mechanisms of two symptoms of schizophrenia: hallucinations and delusions. These two symptoms form the syndrome of psychosis, an immensely disabling psychiatric condition where patients lose their ability for reality testing.


Typically, patients with more severe hallucinations also have more severe delusions, and these two symptoms respond similarly to antipsychotic medications. But this is not always the case as some patients might have very prominent hallucinations but less severe delusions and vice versa. This suggests that these symptoms may share a common neurobiological mechanism while simultaneously depending on symptom-specific pathways.


Some experts in the field believe that a hierarchical perceptual-inference model can explain the mechanisms behind psychosis. The researchers believe that in its simplest form, the hierarchical model has two levels to the hierarchy: low and high. The low level makes inferences about basic features of stimuli and the high level makes inferences about their causes.


An intuitive example of this is inferring the weather. In this scenario, you must decide if you are going to take an umbrella with you when you leave the house. The stimulus in this scenario is what you see when you look out the window; let’s say it’s cloudy. The context in this scenario is what you expect the weather to be like on a given day in the city you are in; let’s say you are in Seattle. Although it is not currently raining, because it’s cloudy and you are in a city where it often rains, you may decide to take an umbrella with you.


The hierarchical model of psychosis frames hallucinations as resulting from dysfunction at the lower levels of the hierarchy and delusions as resulting from dysfunction at the higher levels of the hierarchy. Critically, these levels of inference are distinct but interconnected, so a dysfunction at one level would likely propagate upwards or downwards to other levels, therefore explaining why these symptoms tend to co-occur.


To investigate the neurobiological mechanisms of hallucinations and delusions within the framework of the hierarchical model, the researchers used functional magnetic resonance imaging to measure intrinsic neural timescales throughout the brain. These neural timescales reflect how long information is integrated into a given brain region. Most importantly, these neural timescales are organized hierarchically, making it a fitting measure to test the hierarchical model of psychosis.


The researchers collected data from 127 patients with schizophrenia from various online databases and determined how an individual’s neural timescales related to their hallucination and delusion severities together. They found that neural timescales in the lower levels of the hierarchy tended to be longer in patients with more severe hallucinations, while neural timescales in the higher levels tended to be longer in patients with more severe delusions.


These results provide the first direct evidence of a potential neurobiological mechanism for hallucinations and delusions that fits within the hierarchical model of psychosis and can explain their clinical presentation. The common neurobiological mechanism for both symptoms could result in increased neural timescales, but the symptom-specific pathways are the level of the hierarchy at which the neural timescales are increased.


Their findings have the potential to open the door for the development of treatments to target specific symptoms of psychosis depending on an individual subject’s symptom profile, in line with the current push for individualized medicine.


The overlap of relationships between temporal hypometabolism and both poor memory and delusions suggests that an inability to recall information and delusional thoughts has shared functional underpinnings.


Similarly, hallucinations are a feature of human experience that crosses diagnostic category boundaries and straddles the divide between psychopathological and nonclinical experience. They occur widely across diagnostic disorders and their presence or absence is only clinically useful when considered in conjunction with other symptoms and clinically relevant data.


It is important that researchers continue to study the psychological, biological, and neurological mechanisms behind hallucinations and delusions as solutions to these issues can help many people who are facing different mental health issues.



References:

1. Kenneth Wengle, Andrew T Goldberg, George Chahine, Guillermo Horga. Distinct hierarchical alterations of intrinsic neural timescales account for different manifestations of psychosis. eLife. 2020.

2. Sultzer DL, Leskin LP, Melrose RJ, Harwood DG, Narvaez TA, Ando TK, Mandelkern MA. Neurobiology of delusions, memory, and insight in Alzheimer's disease. The American Journal of Geriatric Psychiatry. 2014.

3. Waters F, Fernyhough C. Hallucinations: a systematic review of points of similarity and difference across diagnostic classes. Schizophrenia Bulletin. 2017.

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