M52. VOICES IN THE HEAD: AUDITORY VERBAL HALLUCINATIONS (AVH) IN HEALTHY INDIVIDUALS

Abstract Background Auditory verbal hallucinations (AVH) are conscious sensory experiences occurring in the absence of external stimulation. AVH are experienced by 75% of individuals diagnosed with schizophrenia and can manifest in other neuropsychiatric disorders. However, AVH are also reported amongst healthy individuals. This implies that hearing voices is not necessarily linked to psychopathology. Amongst voice hearers, the likelihood of AVH seems to reflect individual differences in hallucination proneness (HP). The HP construct allows placing individuals on a psychosis continuum ranging from non-clinical to clinical experiences. Clinical voice hearers tend to misattribute internal events to external sources (externalization bias). Specifically, they seem to experience altered sensory feedback in response to self-initiated stimuli: Although more predictable, clinical voice hearers show similar, neurophysiological responses in reaction to self-initiated vs. externally presented stimuli. EEG studies suggest that this aberrance of prediction is associated with diminished N1-suppression effects that are observed in healthy individuals in response to self-initiated stimuli. Accordingly, clinical voice hearers may have problems differentiating between self-initiated and externally generated speech, potentially leading to externalization of their own speech. In line with this proposal, the current study focusses on non-clinical aspects of the psychosis continuum in healthy voice hearers and controls. This approach avoids confounding factors (medication, disease onset/duration etc.) that typically impede comparisons of clinical and non-clinical voice hearers. By utilizing insights on prediction from the forward model concept within the auditory-sensory domain, we want to investigate how N1-amplitudes in reaction to one’s own or someone else’s voice are modulated as a function of HP. Next to ascertaining the mechanism behind AVH, this research could give direction to identifying risk factors that potentiate the emergence of first-incidence psychosis. Methods HP was assessed by means of the Launay-Slade Hallucination Scale. Each participant’s voice was recorded prior to EEG data acquisition (monosyllabic utterances, “ah” & “oh”, duration = 500 ms). Voice stimuli were morphed with an anchor voice, so that voice identity could be alternated from self- to other-voice (0%, 40%, 50%, 60%, 100%). To contrast neurophysiological responses between self- vs. externally generated voice stimuli, a well-established motor-to-auditory paradigm was used: In a motor-to-auditory condition (MAC) participants were prompted to press a button, thereby eliciting a voice stimulus (self-initiation). In an auditory-only condition (AOC), participants were prompted to passively listen to the voice stimulus (external generation). The motor-only condition (MOC), in which participants executed the button press only, served as a control condition to correct for motor activity in MAC. Results Data from 38 participants replicate the classical N1-suppression effects for self-initiated vs. externally generated self-voice stimuli. This pattern of suppression is also visible for other-voice stimuli. Furthermore, current findings seem to replicate reversed N1-suppression for self-voice in individuals with high HP. Discussion Preliminary findings suggest that HP modulates voice identity processing. More specifically, HP determines how voice stimuli are processed within the internal and external domain. Particularly, individuals with high HP show a reversal of N1-suppression for self-voice stimuli, which corroborates the external biasing hypothesis.

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Neural activity precedes conscious awareness of being in or out of a transient hallucinatory state

10.1101/2020.03.17.995282 ◽

2020 ◽

Author(s):

Kenneth Hugdahl ◽

Alexander R. Craven ◽

Erik Johnsen ◽

Lars Ersland ◽

Drozdstoy Stoyanov ◽

...

Keyword(s):

Neural Activity ◽

Button Press ◽

Conscious Awareness ◽

Response Button ◽

Hearing Voices ◽

Auditory Verbal Hallucinations ◽

Before And After ◽

Neurological Patients ◽

Time Courses ◽

The Mind

SummaryAuditory verbal hallucinations, or “hearing voices”, is a remarkable state of the mind, occurring in psychiatric and neurological patients, and in a significant minority of the general population. An unexplained characteristic of this phenomenon is that it transiently fluctuates, with coming and going of episodes with time. We monitored neural activity with BOLD-fMRI second-by-second before and after participants indicated the start and end of a transient hallucinatory episode during the scanning session by pressing a response-button. We show that a region in the ventro-medial frontal cortex is activated in advance of conscious awareness of going in or out of a transient hallucinatory state. There was an increase in activity initiated a few seconds before the button-press for onsets, and a corresponding decrease in activity initiated a few seconds before the button-press for offsets. We identified the time between onset and offset button-presses, extracted the corresponding BOLD time-courses from nominated regions-of-interest, and analyzed changes in the signal from 10 seconds before to 15 seconds after the response-button was pressed, which identified onset and offset events. We suggest that this brain region act as a switch to turn on and off a hallucinatory episode. The results may have implications for new interventions for intractable hallucinations.

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Reconciling competing mechanisms posited to underlie auditory verbal hallucinations

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0702 ◽

2020 ◽

Vol 376 (1817) ◽

pp. 20190702 ◽

Cited By ~ 1

Author(s):

Katharine N. Thakkar ◽

Daniel H. Mathalon ◽

Judith M. Ford

Keyword(s):

Sensory Stimulation ◽

Mental Illnesses ◽

Sense Of Agency ◽

Predictive Processing ◽

Action Perception ◽

External Stimulation ◽

Hearing Voices ◽

Auditory Verbal Hallucinations ◽

Sensory Data ◽

Past Experiences

Perception is not the passive registration of incoming sensory data. Rather, it involves some analysis by synthesis, based on past experiences and context. One adaptive consequence of this arrangement is imagination—the ability to richly simulate sensory experiences, interrogate and manipulate those simulations, in service of action and decision making. In this paper, we will discuss one possible cost of this adaptation, namely hallucinations—perceptions without sensory stimulation, which characterize serious mental illnesses like schizophrenia, but which also occur in neurological illnesses, and—crucially for the present piece—are common also in the non-treatment-seeking population. We will draw upon a framework for imagination that distinguishes voluntary from non-voluntary experiences and explore the extent to which the varieties and features of hallucinations map onto this distinction, with a focus on auditory-verbal hallucinations (AVHs)—colloquially, hearing voices. We will propose that sense of agency for the act of imagining is key to meaningfully dissecting different forms and features of AVHs, and we will outline the neural, cognitive and phenomenological sequelae of this sense. We will conclude that a compelling unifying framework for action, perception and belief—predictive processing—can incorporate observations regarding sense of agency, imagination and hallucination. This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.

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Correlation of the commercial anti-SARS-CoV-2 receptor binding domain antibody test with the chemiluminescent reduction neutralizing test and possible detection of antibodies to emerging variants

10.1101/2021.05.25.21257828 ◽

2021 ◽

Author(s):

Yoshitomo Morinaga ◽

Hideki Tani ◽

Yasushi Terasaki ◽

Satoshi Nomura ◽

Hitoshi Kawasuji ◽

...

Keyword(s):

Receptor Binding ◽

Disease Onset ◽

Antibody Test ◽

Binding Domain ◽

Receptor Binding Domain ◽

Healthy Individuals ◽

Wild Type ◽

Serum Samples ◽

Serological Tests ◽

Convalescent Phase

Background Serological tests are beneficial for recognizing the immune response against SARS-CoV-2. To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT), using pseudotyped SARS-CoV-2, is critical. Whether commercial antibody tests are comparably accurate is unknown. Methods Serum samples collected before variants were locally found were obtained from confirmed COVID-19 patients (n = 74), confirmed non-COVID-19 individuals (n = 179), and unscreened individuals (suspected healthy individuals, n = 229). The convalescent phase was defined as the period after day 10 from disease onset. The CRNT against pseudotyped viruses displaying the wild-type spike protein and a commercially available anti-receptor binding domain (RBD) antibody test were assayed. The CRNT was also assayed, using South African (SA) and United Kingdom (UK)-derived variants. Results The CRNT (cut off value, 50% inhibition) and the anti-RBD antibody test (cut off value, 0.8 U/mL) concurred regarding symptomatic COVID-19 patients in the convalescent phase and clearly differentiated between patients and suspected healthy individuals (sensitivity; 95.8% and 100%, specificity; 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titer (r = 0.47, 95% CI 0.20-0.68). Compared with the wild-type, CRNT reduction was observed for the SA and UK-derived variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the UK and the SA variants, respectively. Conclusion The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. The strong positive results using the commercial antibody test can reflect neutralizing activity against emerging variants.

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Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

eLife ◽

10.7554/elife.63033 ◽

2021 ◽

Vol 10 ◽

Author(s):

◽

Heli Julkunen ◽

Anna Cichońska ◽

P Eline Slagboom ◽

Peter Würtz

Keyword(s):

General Population ◽

Disease Onset ◽

Severe Pneumonia ◽

Blood Sampling ◽

Low Grade ◽

Healthy Individuals ◽

Metabolic Biomarkers ◽

Low Grade Inflammation ◽

Increased Susceptibility

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.

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Book Review: Hearing voices: the histories, causes and meanings of auditory verbal hallucinations

Australasian Psychiatry ◽

10.1177/1039856213486304 ◽

2013 ◽

Vol 21 (4) ◽

pp. 407-408

Author(s):

Nick O’Connor

Keyword(s):

Hearing Voices ◽

Auditory Verbal Hallucinations

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M187. A MULTIMODAL, NEUROIMAGING STUDY OF TDCS MECHANISMS RELATED TO AUDITORY VERBAL HALLUCINATIONS IN HEALTHY INDIVIDUALS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.499 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S207-S207

Author(s):

Marquardt Lynn ◽

Isabella Kusztrits ◽

Alexander R Craven ◽

Kenneth Hugdahl ◽

Karsten Specht ◽

...

Keyword(s):

Electric Field ◽

Mr Spectroscopy ◽

Dichotic Listening ◽

Block Design ◽

Brain Activation ◽

Healthy Individuals ◽

Auditory Verbal Hallucinations ◽

Sham Stimulation ◽

Dichotic Listening Task ◽

Listening Task

Abstract Background Transcranial direct current stimulation (tDCS) is a brain stimulation method which is growing in popularity in both research and clinical settings, especially as a treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia. However, the underlying neural mechanisms of this tDCS treatment are poorly understood. Current AVH models propose that AVH arise from hyperactivation in the left temporo parietal (LTPC), causing AVH, and from hypoactivation in the left dorsolateral prefrontal cortex (LDLPFC), leading to diminished control over AVH. We aimed to “mimic” this hyper-/hypoactivation pattern in healthy individuals with tDCS by placing the excitatory anode above the LTPC and the inhibitory cathode over the LDLPFC and then to study the effects of tDCS on these brain areas. Previous studies examined either brain activation, neurochemistry, or behavior, with other electrode montages, but few looked at those aspects together. The present study therefore examined tDCS effects with fMRI (functional magnetic resonance imaging), MR spectroscopy, behavioral tasks and simulation of the electric field in a multimodal approach. We hypothesized that tDCS would (a) lead to similar behavioral deficits in healthy individuals as in schizophrenia patients and (b) induce changes in the stimulated areas on neurotransmitter and functional activation level. Methods Thirty-two healthy participants (18 males, mean age=26 yrs) were tested twice, ca. one week apart, with either real or sham (control) 2mA tDCS for 20 min while in a GE 750, 3T MRI scanner. The order of real/sham stimulation was counterbalanced in a double-blind design. During fMRI, participants completed a dichotic listening task in a block design, in order to measure behavior and brain activation changes. Before and after fMRI/tDCS, MR spectroscopy was carried out in two voxels placed under the electrodes. The data was analyzed with repeated measures ANOVAs. After data-collection, the structural T1 sequence was used to simulate the electric field of tDCS stimulation. Results Glx (Glutamate and glutamine combined) showed a trend (F(1,31)=3.35, p=.077, η2p=.098) to increase after tDCS stimulation compared to before, however this was not electrode specific. Neither fMRI, nor the dichotic listening task (all F≤1.64, p≥.203, η2p≤.052) showed any stimulation specific differences between real and sham stimulation. The tDCS simulation revealed large individual differences in the electric field induced. Discussion In the present study, tDCS seemed to have little effect on the measured brain parameters and little validation for the AVH model was found. The mechanisms of tDCS and how it affects the underlying brain tissue are poorly understood and seem to be affected by different stimulation parameters like stimulation duration, current strength and electrode montage. To use tDCS most effectively in schizophrenia research and treatment of auditory hallucinations, it should be validated with a multitude of methods, similar to the approach described here.

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COMT-Val158Met polymorphism modulates antipsychotic effects on auditory verbal hallucinations and temporal lobe gray matter volumes in healthy individuals—symptom relief accompanied by worrisome volume reductions

Brain Imaging and Behavior ◽

10.1007/s11682-019-00043-5 ◽

2019 ◽

Vol 14 (5) ◽

pp. 1373-1381 ◽

Cited By ~ 1

Author(s):

Chuanjun Zhuo ◽

Langlang Cheng ◽

Gongying Li ◽

Yong Xu ◽

Rixing Jing ◽

...

Keyword(s):

Temporal Lobe ◽

Gray Matter ◽

Psychiatric Symptoms ◽

Symptom Relief ◽

Antipsychotic Treatment ◽

Healthy Individuals ◽

Auditory Verbal Hallucinations ◽

Comt Val158met ◽

Magnetic Resonance Imaging Mri ◽

Gray Matter Volumes

Abstract Investigation of auditory verbal hallucinations (AVHs) in schizophrenics is complicated by psychiatric symptoms. Investigating healthy individuals with AVHs (H-AVHs) can obviate such confounding factors. The objective of this study was to explore the effects of antipsychotic treatment on AVHs and gray matter volumes (GMVs) in H-AVH subjects and whether such are effects are influenced by COMT-Val158Met genotype. Magnetic resonance imaging (MRI) and genotyping studies were completed for 42 H-AVH subjects and 42 well-matched healthy controls (HCs). COMT-Met/Met homozygotes (158th codon) were identified as COMT-Met genotype; COMT-Met/Val heterozygotes and COMT-Val/Val homozygotes were identified as COMT-Val genotype. Data were compared across groups (H-AVH vs. HC, and between genotypes) with two-sample t-tests. The H-AVH COMT-Met group showed a stronger response to antipsychotic treatment than the H-AVH COMT-Val group (p < 0.001). Both H-AVH genotype groups exhibited temporal lobe GMV reductions after treatment, and relative to their respective genotype-matched HC groups. Antipsychotic treatment effects in H-AVH subjects were influenced by COMT-Val158Met genotype and associated with widespread GMV reductions. These findings provide clues for further exploration of treatment targets for AVHs. Treatment associated GMV reductions, however, raise concerns about use of antipsychotics in H-AVH subjects.

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Without insight accompanied with deteriorated brain functional alterations in healthy individuals with auditory verbal hallucinations: a pilot study

Brain Imaging and Behavior ◽

10.1007/s11682-019-00207-3 ◽

2019 ◽

Vol 14 (6) ◽

pp. 2553-2558

Author(s):

Chuanjun Zhuo ◽

Feng Ji ◽

Xiaodong Lin ◽

Hongjun Tian ◽

Lina Wang ◽

...

Keyword(s):

Dorsolateral Prefrontal Cortex ◽

Primary Auditory Cortex ◽

Superior Temporal Gyrus ◽

Healthy Individuals ◽

Supramarginal Gyrus ◽

Functional Connectivity Density ◽

Auditory Verbal Hallucinations ◽

Functional Differences ◽

Dorsolateral Prefrontal ◽

Functional Patterns

AbstractFew studies have reported on brain functional differences between healthy individuals with auditory verbal hallucinations (Hi-AVH) with and without insight, so we designed a study to address this knowledge gap. We enrolled 12 Hi-AVH with insight, 15 Hi-AVH without insight, and 15 AVH-free controls (Healthy controls). Global functional connectivity density (gFCD) mapping was used to estimate brain networks. We found that the most common alterations in both Hi-AVH groups were increased gFCD in superior parietal lobule and superior temporal gyrus. We also found that distinct brain functional patterns of Hi-AVH without insight comprised lower gFCD in the frontal lobe oculomotor area, dorsolateral prefrontal cortex, supramarginal gyrus, primary auditory cortex, sensorimotor cortex, ventral anterior, and posterior cingulate Our pilot findings support the hypothesis that abnormal reciprocal action in the circuits for processing perception, memory, language, and attentional control may be pathological features of auditory verbal hallucinations.

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