Access to the video of the session
In the study of schizophrenia spectrum disorders, one of the most established neurophysiological paradigms is the impairment of corollary discharge. Under normal physiological conditions, when we speak or perform an action, the brain sends an efferent motor-to-sensory signal that attenuates the response of the auditory cortex—reflected in a reduced amplitude of the N100 (or N1) event-related potential. This attenuation allows us to differentiate self-generated stimuli from external sounds.
Historically, patients with schizophrenia have been observed to exhibit reduced N100 attenuation during the Talk-Listen paradigm, which has classically correlated with the severity of abnormal self-experiences (measured by scales such as EASE/iPase) and the blurring of self boundaries.
However, findings presented by the SUCEDE Research Group in their session on September 24, 2026, challenge this dogma by analyzing the signal stratified by cognitive biotypes rather than in an aggregated manner.
A Counterintuitive Finding: The Biotype 1 “Paradox”
Based on the clinical stratification developed by the group, a matched cohort was compared comprising healthy controls (n=32), Biotype 1 patients (n=23, characterized by severe cognitive impairment and elevated abnormal self-experience scores), and Biotype 2 patients (n=29, with preserved cognition).
The classical biomedical hypothesis suggested that Biotype 1, presenting greater clinical and cognitive severity, would show the most severe deficit in N100 suppression. The results revealed precisely the opposite:
- Biotype 1 (Severe cognitive impairment): Exhibited practically intact N100 attenuation, remaining within a range comparable to healthy controls.
- Biotype 2 (Preserved cognition): Displayed a drastic reduction in N100 attenuation, with a significant proportion of participants registering negative values.
- Uncoupling of correlations: The inverse correlation between N100 attenuation and the severity of abnormal self-experiences was maintained exclusively in Biotype 2. In Biotype 1, this association disappeared completely.
Pathophysiological Reinterpretation: Divergent Neurobiological Origins
How is it possible that the group with the most pronounced distortion of self-experience maintains a preserved N100 mechanism?
The explanation formulated by the group indicates that abnormal self-experiences do not constitute a biologically monolithic construct, but rather stem from different pathophysiological sources depending on the biotype:
- In Biotype 2 (Preserved cognition): Symptoms of self-disturbance are directly driven by a failure in corollary discharge (fronto-temporal connectivity networks / failure in the N100 preparatory signal).
- In Biotype 1 (Cognitive impairment): The origin of abnormal self-experience does not stem from the N100 circuit, but from other altered biological mechanisms, such as global basal hyperactivity, working memory deficits, or broader structural alterations.
This divergence demonstrates that grouping all patients under a single nosological label (e.g., schizophrenia vs. bipolar disorder) dilutes and masks real neurobiological correlates. The distribution of traditional clinical diagnoses or episode status (first-episode vs. chronic) does not account for this differentiation between biotypes.
Translational Relevance and Next Steps
These findings have been submitted for publication to Schizophrenia Bulletin and are currently under peer review.
Additionally, the group plans to explore independent replication of this pattern in international cohorts, leveraging established connections with research laboratories in Copenhagen that apply similar paradigms in clinical samples.
This discovery reinforces the need to move away from uniform diagnostic categories and advance neurophysiological markers that allow schizophrenia to be addressed through its true biological endophenotypes.