Role of Inferior Colliculi in Auditory Hallucinations

Official title

Rôle Des Colliculi inférieurs Dans Les Hallucinations Auditives : étude Pilote Par Neuroimagerie

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.

Interventions

• Other Unenhanced brain MRI
  Unenhanced brain MRI in five sequences: 1) T1-weighted anatomical sequences 2) Resting-state functional sequences 3) Task-based functional sequence 4) Structural sequence using Diffusion Tensor Imaging (DTI) 5) Routine magnetic resonance spectroscopy sequence

Primary outcome measures

• Resting state of functional connectivity of the inferior colliculi region with other regions of the auditory network between groups [Time frame: Day 0]
• Default mode network patterns between groups [Time frame: Day 0]

Secondary outcome measures (11)

• Neuronal activation in the ICs during exposure to auditory stimuli between groups [Time frame: Day 0]
• Per-auditory activation in other brain areas between groups [Time frame: Day 0]
• IC metabolite composition between the groups [Time frame: Day 0]
• Structural connectivity via white matter between ICs and other auditory network structures between groups [Time frame: Day 0]
• Correlation between BOLD signal and psychopathological symptoms [Time frame: Day 0]
• Correlation between BOLD signal and severity of delusions and hallucinations [Time frame: Day 0]
• Correlation between BOLD signal and doses of antipsychotic treatment [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 [Time frame: Day 0]
• Correlation between BOLD signal and dissociation symptoms [Time frame: Day 0]
• Correlation between BOLD signal and severity of somatoform manifestations of dissociation [Time frame: Day 0]
• Correlation between BOLD signal and clinically assessed states of dissociation [Time frame: Day 0]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• CHU de Nîmes, Hôpital Universitaire Carémeau — Nîmes

Identifiers

NCT: NCT07003529 · NIMAO2024-2/MP-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗