Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• 22q11.2 deletion syndrome (22q11.2DS) is a common genetic variant significantly increasing schizophrenia risk.
• Mismatch negativity (MMN) is a reduced brain response in schizophrenia, indicating impaired change detection.
• Dynamic causal modeling (DCM) has previously shown reduced frontal-temporal connectivity in schizophrenia during MMN tasks.

Purpose of the Study:

• Investigate neural mechanisms of auditory change detection in non-psychotic 22q11.2DS carriers.
• Identify potential early biomarkers for schizophrenia risk within this genetic liability model.
• Examine functional brain connectivity using EEG and DCM.

Main Methods:

• Recorded high-density EEG from 19 non-psychotic 22q11.2DS carriers and 27 healthy controls.
• Utilized a roving oddball paradigm to assess auditory change detection.
• Applied whole-scalp spatiotemporal analysis and DCM to analyze neural responses and connectivity.

Main Results:

• No significant reduction in MMN responses was found in 22q11.2DS carriers.
• A greater fronto-temporal N1 component was observed in carriers.
• DCM indicated reduced intrinsic connectivity in the right auditory cortex and top-down connectivity from the right inferior frontal gyrus to the right superior temporal gyrus, though not surviving multiple comparison correction.

Conclusions:

• Findings suggest altered auditory processing in 22q11.2DS, characterized by reduced adaptation and increased tone sensitivity.
• These neural alterations may represent early functional changes preceding psychosis onset in individuals at high genetic risk for schizophrenia.
• Further research is needed to confirm connectivity findings and their predictive value for schizophrenia.