Discrimination of auditory verbal hallucination in schizophrenia based on EEG brain networks.

Auditory verbal hallucinations (AVH) are a core positive symptom of schizophrenia and are regarded as a consequence of the functional breakdown in the related sensory process. Yet, the potential mechanism of AVH is still lacking. In the present study, we explored the difference between AVHs (n = 23) and non-AVHs (n = 19) in schizophrenia and healthy controls (n = 29) by using multidimensional electroencephalograms data during an auditory oddball task. Compared to healthy controls, both AVH and non-AVH groups showed reduced P300 amplitudes. Additionally, the results from brain networks analysis revealed that AVH patients showed reduced left frontal to posterior parietal/temporal connectivity compared to non-AVH patients. Moreover, using the fused network properties of both delta and theta bands as features for in-depth learning made it possible to identify the AVH from non-AVH patients at an accuracy of 80.95%. The left frontal-parietal/temporal networks seen in the auditory oddball paradigm might be underlying biomarkers of AVH in schizophrenia. This study demonstrated for the first time the functional breakdown of the auditory processing pathway in the AVH patients, leading to a better understanding of the atypical brain network of the AVH patients.

Robotically-induced hallucination triggers subtle changes in brain network transitions.

The perception that someone is nearby, although nobody can be seen or heard, is called presence hallucination (PH). Being a frequent hallucination in patients with Parkinson's disease, it has been argued to be indicative of a more severe and rapidly advancing form of the disease, associated with psychosis and cognitive decline. PH may also occur in healthy individuals and has recently been experimentally induced, in a controlled manner during fMRI, using MR-compatible robotics and sensorimotor stimulation. Previous neuroimaging correlates of such robot-induced PH, based on conventional time-averaged fMRI analysis, identified altered activity in the posterior superior temporal sulcus and inferior frontal gyrus in healthy individuals. However, no link with the strength of the robot-induced PH was observed, and such activations were also associated with other sensations induced by robotic stimulation. Here we leverage recent advances in dynamic functional connectivity, which have been applied to different psychiatric conditions, to decompose fMRI data during PH-induction into a set of co-activation patterns that are tracked over time, as to characterize their occupancies, durations, and transitions. Our results reveal that, when PH is induced, the identified brain patterns significantly and selectively increase their transition probabilities towards a specific brain pattern, centred on the posterior superior temporal sulcus, angular gyrus, dorso-lateral prefrontal cortex, and middle prefrontal cortex. This change is not observed in any other control conditions, nor is it observed in association with other sensations induced by robotic stimulation. The present findings describe the neural mechanisms of PH in healthy individuals and identify a specific disruption of the dynamics of network interactions, extending previously reported network dysfunctions in psychotic patients with hallucinations to an induced robot-controlled specific hallucination in healthy individuals.

Longitudinal thalamic white and grey matter changes associated with visual hallucinations in Parkinson's disease.

OBJECTIVE: Visual hallucinations are common in Parkinson's disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical in controlling cortical networks, structural thalamic changes could underlie network dysfunction in PD hallucinations. METHODS: We used whole-brain fixel-based analysis and cortical thickness measures to examine longitudinal white and grey matter changes in 76 patients with PD (15 hallucinators, 61 non-hallucinators) and 26 controls at baseline, and after 18 months. We compared white matter and cortical thickness, adjusting for age, gender, time-between-scans and intracranial volume. To assess thalamic changes, we extracted volumes for 50 thalamic subnuclei (25 each hemisphere) and mean fibre cross-section (FC) for white matter tracts originating in each subnucleus and examined longitudinal change in PD-hallucinators versus non-hallucinators. RESULTS: PD hallucinators showed white matter changes within the corpus callosum at baseline and extensive posterior tract involvement over time. Less extensive cortical thickness changes were only seen after follow-up. White matter connections from the right medial mediodorsal magnocellular thalamic nucleus showed reduced FC in PD hallucinators at baseline followed by volume reductions longitudinally. After follow-up, almost all thalamic subnuclei showed tract losses in PD hallucinators compared with non-hallucinators. INTERPRETATION: PD hallucinators show white matter loss particularly in posterior connections and in thalamic nuclei, over time with relatively preserved cortical thickness. The right medial mediodorsal thalamic nucleus shows both connectivity and volume loss in PD hallucinations. Our findings provide mechanistic insights into the drivers of network imbalance in PD hallucinations and potential therapeutic targets.

Tinnitus-like "hallucinations" elicited by sensory deprivation in an entropy maximization recurrent neural network.

Sensory deprivation has long been known to cause hallucinations or "phantom" sensations, the most common of which is tinnitus induced by hearing loss, affecting 10-20% of the population. An observable hearing loss, causing auditory sensory deprivation over a band of frequencies, is present in over 90% of people with tinnitus. Existing plasticity-based computational models for tinnitus are usually driven by homeostatic mechanisms, modeled to fit phenomenological findings. Here, we use an objective-driven learning algorithm to model an early auditory processing neuronal network, e.g., in the dorsal cochlear nucleus. The learning algorithm maximizes the network's output entropy by learning the feed-forward and recurrent interactions in the model. We show that the connectivity patterns and responses learned by the model display several hallmarks of early auditory neuronal networks. We further demonstrate that attenuation of peripheral inputs drives the recurrent network towards its critical point and transition into a tinnitus-like state. In this state, the network activity resembles responses to genuine inputs even in the absence of external stimulation, namely, it "hallucinates" auditory responses. These findings demonstrate how objective-driven plasticity mechanisms that normally act to optimize the network's input representation can also elicit pathologies such as tinnitus as a result of sensory deprivation.

Preliminary Evidence for Heterogeneity of Beliefs About Auditory Verbal Hallucinations Intent.

ABSTRACT: Perceptions of patient's auditory verbal hallucinations (AVHs), commonly termed voices, have important impacts on their everyday lives. Despite research emphasizing the consequences of malevolent voices, preliminary results suggest that beliefs about voices may not be mutually exclusive. As such, we aimed to characterize the heterogeneity of beliefs about AVHs and describe their clinical correlates. We recruited 78 patients referred to a Voices group therapy for refractory and distressing voices. Based on the Revised Beliefs About Voices Questionnaire, clustering analysis yielded four subgroups of patients with distinct pattern of beliefs about AVHs. These subgroups differed significantly in terms of affective disturbances, engagement, and resistance to their voices. Furthermore, no significant changes in beliefs about voices were observed after 6 weeks. Results of the current study suggest that the heterogeneity regarding the beliefs about AVHs should be targeted in treatment to reduce their associated negative outcomes.

Auditory hallucinations activate language and verbal short-term memory, but not auditory, brain regions.

Auditory verbal hallucinations (AVH, 'hearing voices') are an important symptom of schizophrenia but their biological basis is not well understood. One longstanding approach proposes that they are perceptual in nature, specifically that they reflect spontaneous abnormal neuronal activity in the auditory cortex, perhaps with additional 'top down' cognitive influences. Functional imaging studies employing the symptom capture technique-where activity when patients experience AVH is compared to times when they do not-have had mixed findings as to whether the auditory cortex is activated. Here, using a novel variant of the symptom capture technique, we show that the experience of AVH does not induce auditory cortex activation, even while real speech does, something that effectively rules out all theories that propose a perceptual component to AVH. Instead, we find that the experience of AVH activates language regions and/or regions that are engaged during verbal short-term memory.

Altered states phenomena induced by visual flicker light stimulation.

Flicker light stimulation can induce short-term alterations in consciousness including hallucinatory color perception and geometric patterns. In the study at hand, the subjective experiences during 3 Hz and 10 Hz stroboscopic light stimulation of the closed eyes were assessed. In a within-subjects design (N = 24), we applied the Positive and Negative Affect Schedule (mood state), time perception ratings, the Altered State of Consciousness Rating Scale, and the Phenomenology of Consciousness Inventory. Furthermore, we tested for effects of personality traits (NEO Five-Factor Inventory-2 and Tellegen Absorption Scale) on subjective experiences. Such systematic quantification improves replicability, facilitates comparisons between pharmacological and non-pharmacological techniques to induce altered states of consciousness, and is the prerequisite to study their underlying neuronal mechanisms. The resulting data showed that flicker light stimulation-induced states were characterized by vivid visual hallucinations of simple types, with effects strongest in the 10 Hz condition. Additionally, participants' personality trait of Absorption scores highly correlated with the experienced alterations in consciousness. Our data demonstrate that flicker light stimulation is capable of inducing visual effects with an intensity rated to be similar in strength to effects induced by psychedelic substances and thereby support the investigation of potentially shared underlying neuronal mechanisms.

Deficits in multi-scale top-down processes distorting auditory perception in schizophrenia.

Cognitive models postulate that impaired source monitoring incorrectly weights the top-down prediction and bottom-up sensory processes and causes hallucinations. However, the underlying mechanisms of the interaction, such as whether the incorrectly weighting is ubiquitously on all levels of sensory features and whether different top-down processes have distinct effects in subgroups of schizophrenia are still unclear. This study investigates how multi-scale predictions influence perception of basic tonal features in schizophrenia. Sixty-three schizophrenia patients with and without symptoms of auditory verbal hallucinations (AVHs), and thirty healthy controls identified target tones in noise at the end of tone sequences. Predictions of different timescales were manipulated by either an alternating pattern in the preceding tone sequences (long-term regularity) or a repetition between the target tone and the tone immediately before (short-term repetition). The sensitivity index, d prime (d'), was obtained to assess the modulation of predictions on tone identification. Patients with AVHs showed higher d' when the target tones conformed to the long-term regularity of alternating pattern in the preceding tone sequence than when the target tones were inconsistent with the pattern. Whereas, the short-term repetition modulated the tone identification in patients without AVHs. Predictions did not influence tone identification in healthy controls. Our results suggest that impaired source monitoring in schizophrenia patients with AVHs heavily weights top-down predictions over bottom-up perceptual processes to form incorrect perception. The weighting function in source monitoring can extend to the processes of basic tonal features, and predictions at multiple timescales could differentially modulate perception in different clinical populations. The impaired interaction between top-down and bottom-up processes might underlie the development of hallucination symptoms in schizophrenia.

Beyond imagination: Hypnotic visual hallucination induces greater lateralised brain activity than visual mental imagery.

Hypnotic suggestions can produce a broad range of perceptual experiences, including hallucinations. Visual hypnotic hallucinations differ in many ways from regular mental images. For example, they are usually experienced as automatic, vivid, and real images, typically compromising the sense of reality. While both hypnotic hallucination and mental imagery are believed to mainly rely on the activation of the visual cortex via top-down mechanisms, it is unknown how they differ in the neural processes they engage. Here we used an adaptation paradigm to test and compare top-down processing between hypnotic hallucination, mental imagery, and visual perception in very highly hypnotisable individuals whose ability to hallucinate was assessed. By measuring the N170/VPP event-related complex and using multivariate decoding analysis, we found that hypnotic hallucination of faces involves greater top-down activation of sensory processing through lateralised neural mechanisms in the right hemisphere compared to mental imagery. Our findings suggest that the neural signatures that distinguish hypnotically hallucinated faces from imagined faces lie in the right brain hemisphere.

Ninety Years of Multiple Psychotic-Like and Spiritual Experiences in a Doctor Honoris Causa: A Case Report and Literature Review.

ABSTRACT: Psychotic experiences are common experiences shared by a considerable part of the world's population. Moreover, most of the individuals who report these experiences also report those called spiritual and dissociative phenomena. In specific culture and religious backgrounds, these experiences are frequently seen as a part of normal human experiences, usually called mediumship. We report a case of a famous Brazilian medium with 90 years of experiencing psychotic-like, dissociative and/or spiritual experiences, but coped well with the experiences and never sought psychiatric or psychological assistance. The medium received several honorific prizes, such as doctor honoris causa from different institutions, published more than 200 books, and ran a nonprofit organization that takes care of 5000 people daily. Finally, we review the literature on this topic and stress the urge for more research aiming to distinguish pathological and nonpathological psychotic experiences to avoid overmedicalization and iatrogenic treatments.

Associations between visual hallucinations and impaired visuo-spatial abilities in dementia with Lewy bodies.

Objectives: In dementia with Lewy bodies (DLB) recurrent visual hallucinations (VH) often coexist or occur consecutively to impaired visual perception. Since in-depth neuropsychological testing is time-consuming, and therefore, not routinely performed in clinical settings, we aimed to explore whether standard cognitive screening tests may be helpful to alert a clinician to the presence of VH in DLB by exploring association between visuo-spatial dysfunction and VH. Method: The clock drawing, cube, and pentagons copying items from Montreal Cognitive Assessment and Mini-Mental State Exam and nonmotor Hooper visual organization test (HVOT) have been scored in DLB patients with and without VH using traditional and extended scoring methods. Results: Forty-five of 69 (65%) DLB patients were VH-positive (VH+). VH+ patients performed worse on the clock drawing (8.8/16 vs. 11.9/16, p = .016) with a higher rate of misrepresentation of time (69% vs. 29%, p = .002) and numbers (53% vs. 25%, p = .024). Likewise, VH+ patients performed worse on the HVOT (13.3/30 vs. 15.7/30, p = .009) having more isolated (6.2/30 vs. 4.4/30, p = .012) types of responses compared to VH- patients. Both groups had similar copying ability (p > .05). The VH discriminative accuracy of the clock drawing was comparable to that of the more elaborate test of visual perception, the HVOT. Conclusions: In DLB impaired drawing and visual organization, but not copying ability is associated with the presence of VH. The simple clock drawing test can be helpful to alert a clinician to the possibility of VH in DLB. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Clinical Phenotypes of Behavioral Variant Frontotemporal Dementia by Age at Onset.

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is generally considered a young-onset dementia, although age at onset is highly variable. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. OBJECTIVE: We aimed to examine behavior, cognition, and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic, or histopathological confirmation and exclusion of positive Alzheimer's disease biomarkers or severe cerebrovascular damage. METHODS: In total, 315 patients with a clinical diagnosis of probable or definite bvFTD were included from the Amsterdam Dementia Cohort and grouped into quartiles by age-at-diagnosis. Neuropsychiatric symptoms and cognitive functioning were assessed with the neuropsychiatric inventory, the geriatric depression scale and a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Associations between age-at-diagnosis and clinical features and mortality risk were examined. RESULTS: Age-at-diagnosis ranged from 26 to 85 years and established quartiles with mean ages of 52±6, 61±2, 66±2, and 74±3 years. In the total sample, 44.4%exceeded an age of 65 years at time of diagnosis. Earlier age-at-diagnosis was associated with more severe behavioral symptoms, while later age-at-diagnosis was associated with more severe memory impairment. Unexpectedly, mortality risk was not associated with age-at-diagnosis. CONCLUSION: In bvFTD, symptom profile is associated with age-at-diagnosis. This should be taken into account with regard to diagnostics, patient management, and trial design. Additionally, based on our sample, the prevalence of late-onset bvFTD is higher than generally thought.

Striatal dopamine mediates hallucination-like perception in mice.

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

Fronto-Temporal Disconnection Within the Presence Hallucination Network in Psychotic Patients With Passivity Experiences.

Psychosis, characterized by hallucinations and delusions, is a common feature of psychiatric disease, especially schizophrenia. One prominent theory posits that psychosis is driven by abnormal sensorimotor predictions leading to the misattribution of self-related events. This misattribution has been linked to passivity experiences (PE), such as loss of agency and, more recently, to presence hallucinations (PH), defined as the conscious experience of the presence of an alien agent while no person is actually present. PH has been observed in schizophrenia, Parkinson's disease, and neurological patients with brain lesions and, recently, the brain mechanisms of PH (PH-network) have been determined comprising bilateral posterior middle temporal gyrus (pMTG), inferior frontal gyrus (IFG), and ventral premotor cortex (vPMC). Given that the experience of an alien agent is a common feature of PE, we here analyzed the functional connectivity within the PH-network in psychotic patients with (N = 39) vs without PE (N = 26). We observed reduced fronto-temporal functional connectivity in patients with PE compared to patients without PE between the right pMTG and the right and left IFG of the PH-network. Moreover, when seeding from these altered regions, we observed specific alterations with brain regions commonly linked to auditory-verbal hallucinations (such as Heschl's gyrus). The present connectivity findings within the PH-network extend the disconnection hypothesis for hallucinations to the specific case of PH and associates the PH-network with key brain regions for frequent psychotic symptoms such as auditory-verbal hallucinations, showing that PH are relevant to the study of the brain mechanisms of psychosis and PE.

Auditory signal detection in schizophrenia: Correlates with auditory verbal hallucinations & effect of single session transcranial direct current stimulation (tDCS).

INTRODUCTION: Transcranial Direct Current Stimulation (tDCS) has been beneficial for treating auditory verbal hallucinations (AVH) in schizophrenia (SZ). Aberrant auditory signal detection (ASD) is one of the pathogenetic mechanisms for AVH. We investigated the correlates of ASD with AVH and the impact of single-session tDCS on ASD in SZ patients. METHODS: The ASD performance in SZ patients was compared with matched healthy controls (HC) (N = 24). Subsequently, the effect of single-session tDCS on ASD in SZ patients (N = 24) with AVH was examined in a randomized, double-blind, sham-controlled, cross-over design. The true and sham tDCS were administered (anode at the left dorsolateral prefrontal cortex and cathode at the left temporoparietal junction) on two different days. ASD task was performed before and after each session of tDCS. RESULTS: Auditory hallucination rating scores correlated significantly with false alarm rate, discriminability index, and response bias. SZ patients had a significantly lesser discriminability index in ASD than HC. Single-session tDCS (true versus sham) did not have any significant effect on ASD in SZ patients. CONCLUSION: The study findings support the pathogenetic role of ASD in AVH in SZ. Lack of effect on ASD following single-session tDCS suggests the need for multi-session studies in the future.

Functional connectome differences in individuals with hallucinations across the psychosis continuum.

Hallucinations may arise from an imbalance between sensory and higher cognitive brain regions, reflected by alterations in functional connectivity. It is unknown whether hallucinations across the psychosis continuum exhibit similar alterations in functional connectivity, suggesting a common neural mechanism, or whether different mechanisms link to hallucinations across phenotypes. We acquired resting-state functional MRI scans of 483 participants, including 40 non-clinical individuals with hallucinations, 99 schizophrenia patients with hallucinations, 74 bipolar-I disorder patients with hallucinations, 42 bipolar-I disorder patients without hallucinations, and 228 healthy controls. The weighted connectivity matrices were compared using network-based statistics. Non-clinical individuals with hallucinations and schizophrenia patients with hallucinations exhibited increased connectivity, mainly among fronto-temporal and fronto-insula/cingulate areas compared to controls (P < 0.001 adjusted). Differential effects were observed for bipolar-I disorder patients with hallucinations versus controls, mainly characterized by decreased connectivity between fronto-temporal and fronto-striatal areas (P = 0.012 adjusted). No connectivity alterations were found between bipolar-I disorder patients without hallucinations and controls. Our results support the notion that hallucinations in non-clinical individuals and schizophrenia patients are related to altered interactions between sensory and higher-order cognitive brain regions. However, a different dysconnectivity pattern was observed for bipolar-I disorder patients with hallucinations, which implies a different neural mechanism across the psychosis continuum.

Voice-Hearing and Personification: Characterizing Social Qualities of Auditory Verbal Hallucinations in Early Psychosis.

Recent therapeutic approaches to auditory verbal hallucinations (AVH) exploit the person-like qualities of voices. Little is known, however, about how, why, and when AVH become personified. We aimed to investigate personification in individuals' early voice-hearing experiences. We invited Early Intervention in Psychosis (EIP) service users aged 16-65 to participate in a semistructured interview on AVH phenomenology. Forty voice-hearers (M = 114.13 days in EIP) were recruited through 2 National Health Service trusts in northern England. We used content and thematic analysis to code the interviews and then statistically examined key associations with personification. Some participants had heard voices intermittently for multiple years prior to clinical involvement (M = 74.38 months), although distressing voice onset was typically more recent (median = 12 months). Participants reported a range of negative emotions (predominantly fear, 60%, 24/40, and anxiety, 62.5%, 26/40), visual hallucinations (75%, 30/40), bodily states (65%, 25/40), and "felt presences" (52.5%, 21/40) in relation to voices. Complex personification, reported by a sizeable minority (16/40, 40%), was associated with experiencing voices as conversational (odds ratio [OR] = 2.56) and companionable (OR = 3.19) but not as commanding or trauma-related. Neither age of AVH onset nor time since onset related to personification. Our findings highlight significant personification of AVH even at first clinical presentation. Personified voices appear to be distinguished less by their intrinsic properties, commanding qualities, or connection with trauma than by their affordances for conversation and companionship.