Role of Inferior Colliculi in Auditory Hallucinations

Centre Hospitalier Universitaire de Nīmes40 enrolled

Overview

The neural basis of auditory hallucinations (AH) in patients with schizophrenia is poorly characterized. Functional imaging studies investigate either the "state" dimension (i.e., the measurement of changes in brain area activation at the precise moment of AH onset) or the "trait" dimension (i.e., the neural correlates of the propensity to hallucinate). A corollary of AH (particularly acoustic-verbal) is the activation of brain regions involved in the auditory perception of speech (auditory cortex). One theory is that patients with schizophrenia with AH may have a deficit in processing their internal speech (i.e., external attribution to internal verbal content). However, there is little clinical data on the specific role of the mesencephalic region of the inferior colliculi (IC) in the formation of these symptoms. Preliminary research has shown intense expression of dopamine D2 receptors, particularly on glutamatergic neurons in mouse ICs. Thus, ICs receive numerous inhibitory dopaminergic inputs, likely involved in signal optimization and modulation. The study authors hypothesize that AHs are the result of a defect in signal inhibition by the IC, which lose their function as perceptual filters.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Schizophrenia Hallucinations, Auditory

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * The patient must have given their free and informed consent and signed the consent form * The patient must be a member or beneficiary of a health insurance plan * DSM-5 diagnosis of schizophrenic disorder (based on clinical assessment and confirmed by the MINI 7.0 interview) * Patient with a schizophrenic disorder lasting ≤ 20 years * Patient treated in a psychiatric unit as an inpatient (in non-specialized care) or outpatient or under a mandatory ambulatory psychiatric care programme * Clinical condition compatible with imaging based on clinical judgment * Ability to understand, write, and read French Specific inclusion criteria for the group (SCZ+/HA+) • Patient with a PANSS score (question P3 regarding hallucinations) ≥ 4 (corresponds to PANSS (P3) 4, 5, 6, and 7 patients) AND having experienced hallucinations in the past 15 days. Specific inclusion criteria for the control group • Patient with a PANSS score (question P3 regarding hallucinations) = 1) AND having not experienced any hallucinations in the past 15 days. Exclusion Criteria: * The patient is under safeguard of justice or state guardianship * Contraindications to magnetic resonance imaging, including severe claustrophobia, based on clinical judgment. * Congenital or acquired deafness * Suicide risk, based on clinical judgment * Patient with moderate to severe intellectual disability, based on medical records * Patient with moderate to severe neurocognitive disorders, based on medical records * Patient receiving anticholinergic therapy (biperiden-Akineton, trihexyphenidyl-Artane, tropatepine-Lepticur) * Patient participating in an interventional study involving a drug or medical device, or a Category 1 RIPH within 3 months prior to inclusion * Person under judicial protection * Pregnant, parturient, or breastfeeding woman * Person unable to express consent

Outcomes

Primary Outcomes

Resting state of functional connectivity of the inferior colliculi region with other regions of the auditory network between groups

Measured by MRI

Time frame: Day 0

Default mode network patterns between groups

Measured by MRI

Time frame: Day 0

Secondary Outcomes

Neuronal activation in the ICs during exposure to auditory stimuli between groups

Difference in the blood-oxygen level dependent (BOLD) signal measured by functional MRI during an auditory stimulus exposure paradigm in the IC region

Time frame: Day 0

Per-auditory activation in other brain areas between groups

Difference in the BOLD signal measured by functional MRI in other brain areas

Time frame: Day 0

IC metabolite composition between the groups

Difference in the peak magnetic resonance spectrometry (sMRI) signal

Time frame: Day 0

Structural connectivity via white matter between ICs and other auditory network structures between groups

Difference in structural connectivity using DTI (diffusion tensor imaging, anisotropy fraction calculation, mean diffusivity, and tractography) from the ICs

Time frame: Day 0

Correlation between BOLD signal and psychopathological symptoms

Measured by Positive and Negative Syndrome Scale (PANSS), providing a negative symptomatology score ranging from 7 to 49, and a general psychopathology score ranging from 16 to 112, with a total score ranging from 30 to 210.

Time frame: Day 0

Correlation between BOLD signal and severity of delusions and hallucinations

Measured by Psychotic Symptom Rating Scale (PSYRATS), an 11-item scale where each symptom is rated from 0 to 4 depending on the intensity

Time frame: Day 0

Correlation between BOLD signal and doses of antipsychotic treatment

Antipsychotic doses calculated by olanzapine equivalent method

Time frame: Day 0

Difference in perauditory activation and functional connectivity (resting-state) in SCZ+ HA+ patients who hallucinated during the procedure and those who did not

Measured via post-hoc task-based, BOLD signal state hallucination analysis

Time frame: Day 0

Correlation between BOLD signal and dissociation symptoms

Measured by Dissociative Experience Scale (DES)

Time frame: Day 0

Correlation between BOLD signal and severity of somatoform manifestations of dissociation

Measured by Somatoform Dissociation Questionnaire (SDQ)

Time frame: Day 0

Correlation between BOLD signal and clinically assessed states of dissociation

Measured by Clinician Administered Dissociative States Scale (CADSS), a 5-point Likert scale

Time frame: Day 0

Role of Inferior Colliculi in Auditory Hallucinations

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts