Brain Metabolism during Hallucination-Like Auditory Stimulation in Schizophrenia

Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia

Brain metabolism during hallucination-like auditory stimulation in schizophrenia

Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophreni

Sex-specific Neural Activity When Resolving Cognitive Interference In Individuals With Or Without Prior Internalizing Disorders

The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in individuals with and without an illness history of an internalizing disorder. We compared functional magnetic resonance imaging blood-oxygenation-level-dependent responses in both males (n ¼63) and females (n ¼80) with and without this illness history during performance of the Simon task. Females deactivated superior frontal gyrus, inferior parietal lobe, and posterior cingulate cortex to a greater extent than males. Females with a prior history of internalizing disorder also deactivated these regions more compared to males with that history, and they additionally demonstrated greater activation of right inferior frontal gyrus. These group differences were represented in a significant sex-by-illness interaction in these regions. These deactivated regions compose a task-negative or default mode network, whereas the inferior frontal gyrus usually activates when performing an attention-demanding task and is a key component of a task-positive network. Our findings suggest that a prior history of internalizing disorders disproportionately influences functioning of the default mode network and is associated with an accompanying activation of the task-positive network in females during the resolution of cognitive interference

Auditory Hallucinations and the Brain’s Resting-State Networks: Findings and Methodological Observations

In recent years, there has been increasing interest in the potential for alterations to the brain’s resting-state networks (RSNs) to explain various kinds of psychopathology. RSNs provide an intriguing new explanatory framework for hallucinations, which can occur in different modalities and population groups, but which remain poorly understood. This collaboration from the International Consortium on Hallucination Research (ICHR) reports on the evidence linking resting-state alterations to auditory hallucinations (AH) and provides a critical appraisal of the methodological approaches used in this area. In the report, we describe findings from resting connectivity fMRI in AH (in schizophrenia and nonclinical individuals) and compare them with findings from neurophysiological research, structural MRI, and research on visual hallucinations (VH). In AH, various studies show resting connectivity differences in left-hemisphere auditory and language regions, as well as atypical interaction of the default mode network and RSNs linked to cognitive control and salience. As the latter are also evident in studies of VH, this points to a domain-general mechanism for hallucinations alongside modality-specific changes to RSNs in different sensory regions. However, we also observed high methodological heterogeneity in the current literature, affecting the ability to make clear comparisons between studies. To address this, we provide some methodological recommendations and options for future research on the resting state and hallucinations

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles

Altres ajuts: Ajuts per donar Suport als Grups de Recerca de Catalunya," sponsored by the "Agència de Gestió d'Ajuts Universitaris i de Recerca" (AGAUR), Generalitat de CatalunyaWe aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p = 3 × 10 −7 ; odds ratio [OR] = 8.96, 95% confidence interval [CI] = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p = 6 × 10 −4 ; OR = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%. HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration

From Computation to the First-Person : Auditory-Verbal Hallucinations and Delusions of Thought Interference in Schizophrenia-Spectrum Psychoses

Schizophrenia-spectrum psychoses are highly complex and heterogeneous disorders that necessitate multiple lines of scientific inquiry and levels of explanation. In recent years, both computational and phenomenological approaches to the understanding of mental illness have received much interest, and significant progress has been made in both fields. However, there has been relatively little progress bridging investigations in these seemingly disparate fields. In this conceptual review and collaborative project from the 4th Meeting of the International Consortium on Hallucination Research, we aim to facilitate the beginning of such dialogue between fields and put forward the argument that computational psychiatry and phenomenology can in fact inform each other, rather than being viewed as isolated or even incompatible approaches. We begin with an overview of phenomenological observations on the interrelationships between auditory-verbal hallucinations (AVH) and delusional thoughts in general, before moving on to review several theoretical frameworks and empirical findings in the computational modeling of AVH. We then relate the computational models to the phenomenological accounts, with a special focus on AVH and delusions that involve the senses of agency and ownership of thought (delusions of thought interference). Finally, we offer some tentative directions for future research, emphasizing the importance of a mutual understanding between separate lines of inquiry

Conscious and unconscious processes in cognitive control: a theoretical perspective and a novel empirical approach

Controlled processing is often referred to as “voluntary” or “willful” and therefore assumed to depend entirely on conscious processes. Recent studies using subliminal-priming paradigms, however, have started to question this assumption. Specifically, these studies have shown that subliminally presented stimuli can induce adjustments in control. Such findings are not immediately reconcilable with the view that conscious and unconscious processes are separate, with each having its own neural substrates and modus operandi. We propose a different theoretical perspective that suggests that conscious and unconscious processes might be implemented by the same neural substrates and largely perform the same neural computations, with the distinction between the two arising mostly from the quality of representations (although not all brain regions may be capable of supporting conscious representations). Thus, stronger and more durable neuronal firing would give rise to conscious processes; weaker or less durable neuronal firing would remain below the threshold of consciousness but still be causally efficacious in affecting behavior. We show that this perspective naturally explains the findings that subliminally presented primes induce adjustments in cognitive control. We also highlight an important gap in this literature: whereas subliminal-priming paradigms demonstrate that an unconsciously presented prime is sufficient to induce adjustments in cognitive control, they are uninformative about what occurs under standard task conditions. In standard tasks, the stimuli themselves are consciously perceived; however, the extent to which the processes that lead to adjustments in control are conscious or unconscious remains unexplored. We propose a new paradigm suitable to investigate these issues and to test important predictions of our hypothesis that conscious and unconscious processes both engage the same control machinery, differing mostly in the quality of the representations

The parieto-occipital cortex is a candidate neural substrate for the human ability to approximate Bayesian inference

Abstract Adaptive decision-making often requires one to infer unobservable states based on incomplete information. Bayesian logic prescribes that individuals should do so by estimating the posterior probability by integrating the prior probability with new information, but the neural basis of this integration is incompletely understood. We record fMRI during a task in which participants infer the posterior probability of a hidden state while we independently modulate the prior probability and likelihood of evidence regarding the state; the task incentivizes participants to make accurate inferences and dissociates expected value from posterior probability. Here we show that activation in a region of left parieto-occipital cortex independently tracks the subjective posterior probability, combining its subcomponents of prior probability and evidence likelihood, and reflecting the individual participants’ systematic deviations from objective probabilities. The parieto-occipital cortex is thus a candidate neural substrate for humans’ ability to approximate Bayesian inference by integrating prior beliefs with new information